Literature

This section presents a list of the latest published scientific journal articles and preprints on COVID-19 and SARS-CoV-2 where at least one author has a Spanish affiliation. Items have been fetched from an automatic daily search from Europe PMC completed with other elements manually curated and uploaded from researchers.

There are filters at your disposal to navigate the list, i.e. publications with acknowledged funding to the “Fondo COVID19” extraordinary funds. Note that some articles have additional available data that have been curated manually and as such may not be exhaustive.

You can help us enriching this section by adding new papers not listed below or available associated data to existing ones (datasets, code repositories…) by filling in this formulaire. Please make sure that the information is not already in the table below and that the publication has at least one author affiliated in Spain.

Last update: 2022-01-24
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Fondo COVID19
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Year
2020
2021
Publications Published Year Funder Publication type Available abstract Available related data DOI Title Authors Journal
The target landscape of N4-hydroxycytidine based on its chemical neighborhood
Jordi Mestres
preprint  bioRxiv
DOI: 10.1101/2020.03.30.016485
N4-hydroxycytidine (NHC) has been recently reported to have promising antiviral activity against SARS-CoV-2. To join worldwide efforts in identifying potential drug targets against this pandemic, the target landscape of NHC was defined by extracting all known targets of its chemical neighborhood, including drugs, analogues, and metabolites, and by performing target predictions from two independent platforms, following the recent Public Health Assessment via Structural Evaluation (PHASE) protocol. The analysis provides a list of over 30 protein targets that could be useful in future design activities of new COVID-19 antivirals. The relevance for existing drugs within the same chemical space, such as remdesivir, is also discussed.
2020-04-01 2020 other preprint abstract-available data-available 10.1101/2020.03.30.016485 The target landscape of N4-hydroxycytidine based on its chemical neighborhood Jordi Mestres bioRxiv
Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment
Alberto Ferrari, Enrico Santus, Davide Cirillo, Miguel Ponce-de-Leon, [...], Alfonso Valencia
npj Digital Medicine, volume 4, Article number: 9 (2021)
DOI: 10.1038/s41746-020-00374-4
Targeted contact-tracing through mobile phone apps has been proposed as an instrument to help contain the spread of COVID-19 and manage the lifting of nation-wide lock-downs currently in place in USA and Europe. However, there is an ongoing debate on its potential efficacy, especially in light of region-specific demographics. We built an expanded SIR model of COVID-19 epidemics that accounts for region-specific population densities, and we used it to test the impact of a contact-tracing app in a number of scenarios. Using demographic and mobility data from Italy and Spain, we used the model to simulate scenarios that vary in baseline contact rates, population densities, and fraction of app users in the population. Our results show that, in support of efficient isolation of symptomatic cases, app-mediated contact-tracing can successfully mitigate the epidemic even with a relatively small fraction of users, and even suppress altogether with a larger fraction of users. However, when regional differences in population density are taken into consideration, the epidemic can be significantly harder to contain in higher density areas, highlighting potential limitations of this intervention in specific contexts. This work corroborates previous results in favor of app-mediated contact-tracing as mitigation measure for COVID-19, and draws attention on the importance of region-specific demographic and mobility factors to achieve maximum efficacy in containment policies.
2021-01-14 2021 other article abstract-available data-available 10.1038/s41746-020-00374-4 Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment Alberto Ferrari, Enrico Santus, Davide Cirillo, Miguel Ponce-de-Leon, Nicola Marino, Maria Teresa Ferretti, Antonella Santuccione Chadha, Nikolaos Mavridis, Alfonso Valencia npj Digital Medicine, volume 4, Article number: 9 (2021)
RNA-Dependent RNA Polymerase From SARS-CoV-2. Mechanism Of Reaction And Inhibition By Remdesivir
Juan Aranda, Modesto Orozco
preprint  bioRxiv
DOI: 10.1101/2020.06.21.163592
We combine sequence analysis, molecular dynamics and hybrid quantum mechanics/molecular mechanics simulations to obtain the first description of the mechanism of reaction of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and of the inhibition of the enzyme by Remdesivir. Despite its evolutionary youth, the enzyme is highly optimized to have good fidelity in nucleotide incorporation and a good catalytic efficiency. Our simulations strongly suggest that Remdesivir triphosphate (the active form of drug) is incorporated into the nascent RNA replacing ATP, leading to a duplex RNA which is structurally very similar to an unmodified one. We did not detect any reason to explain the inhibitory activity of Remdesivir at the active site. Displacement of the nascent Remdesivir-containing RNA duplex along the exit channel of the enzyme can occur without evident steric clashes which would justify delayed inhibition. However, after the incorporation of three more nucleotides we found a hydrated Serine which is placed in a perfect arrangement to react through a Pinner’s reaction with the nitrile group of Remdesivir. Kinetic barriers for crosslinking and polymerization are similar suggesting a competition between polymerization and inhibition. Analysis of SARS-CoV-2 mutational landscape and structural analysis of polymerases across different species support the proposed mechanism and suggest that virus has not explored yet resistance to Remdesivir inhibition.
2020-06-21 2020 other preprint abstract-available data-available 10.1101/2020.06.21.163592 RNA-Dependent RNA Polymerase From SARS-CoV-2. Mechanism Of Reaction And Inhibition By Remdesivir Juan Aranda, Modesto Orozco bioRxiv
MasterOfPores: A Workflow for the Analysis of Oxford Nanopore Direct RNA Sequencing Datasets
Luca Cozzuto, Huanle Liu, Leszek P. Pryszcz, Toni Hermoso Pulido, [...], Eva Maria Novoa
Front. Genet. 11:211
DOI: 10.3389/fgene.2020.00211
The direct RNA sequencing platform offered by Oxford Nanopore Technologies allows for direct measurement of RNA molecules without the need of conversion to complementary DNA, fragmentation or amplification. As such, it is virtually capable of detecting any given RNA modification present in the molecule that is being sequenced, as well as provide polyA tail length estimations at the level of individual RNA molecules. Although this technology has been publicly available since 2017, the complexity of the raw Nanopore data, together with the lack of systematic and reproducible pipelines, have greatly hindered the access of this technology to the general user. Here we address this problem by providing a fully benchmarked workflow for the analysis of direct RNA sequencing reads, termed MasterOfPores. The pipeline starts with a pre-processing module, which converts raw current intensities into multiple types of processed data including FASTQ and BAM, providing metrics of the quality of the run, quality-filtering, demultiplexing, base-calling and mapping. In a second step, the pipeline performs downstream analyses of the mapped reads, including prediction of RNA modifications and estimation of polyA tail lengths. Four direct RNA MinION sequencing runs can be fully processed and analyzed in 10 h on 100 CPUs. The pipeline can also be executed in GPU locally or in the cloud, decreasing the run time fourfold. The software is written using the NextFlow framework for parallelization and portability, and relies on Linux containers such as Docker and Singularity for achieving better reproducibility. The MasterOfPores workflow can be executed on any Unix-compatible OS on a computer, cluster or cloud without the need of installing any additional software or dependencies, and is freely available in Github (https://github.com/biocorecrg/master_of_pores). This workflow simplifies direct RNA sequencing data analyses, facilitating the study of the (epi)transcriptome at single molecule resolution.
2020-03-17 2020 other article abstract-available data-available 10.3389/fgene.2020.00211 MasterOfPores: A Workflow for the Analysis of Oxford Nanopore Direct RNA Sequencing Datasets Luca Cozzuto, Huanle Liu, Leszek P. Pryszcz, Toni Hermoso Pulido, Anna Delgado-Tejedor, Julia Ponomarenko, Eva Maria Novoa Front. Genet. 11:211
Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations
Lucía Trilla-Fuertes, Ricardo Ramos, Natalia Blanca-López, Elena López-Camacho, [...], Angelo Gámez-Pozo
preprint  bioRxiv
DOI: 10.1101/2020.06.22.164384
Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments.
2020-09-24 2020 other preprint abstract-available data-available 10.1101/2020.06.22.164384 Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations Lucía Trilla-Fuertes, Ricardo Ramos, Natalia Blanca-López, Elena López-Camacho, Laura Martín-Pedraza, Pablo Ryan Murua, Mariana Díaz-Almirón, Carlos Llorens, Toni Gabaldón, Andrés Moya, Juan Ángel Fresno Vara, Angelo Gámez-Pozo bioRxiv
Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection
Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M. Falco, [...], María Peña-Chilet
Sig Transduct Target Ther 5, 290 (2020)
DOI: 10.1038/s41392-020-00417-y
2020-12-11 2020 other article data-available 10.1038/s41392-020-00417-y Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M. Falco, Joaquín Dopazo, María Peña-Chilet Sig Transduct Target Ther 5, 290 (2020)
DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain
Jordi Martorell-Marugán, Juan Antonio Villatoro-García, Adrián García-Moreno, Raúl López-Domínguez, [...], Pedro Carmona-Sáez
Science of The Total Environment, Volume 750, 2021, 141424, ISSN 0048-9697
DOI: 10.1016/j.scitotenv.2020.141424
The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO2, CO, PM2.5, PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es.
2020-06-23 2020 other article abstract-available data-available 10.1016/j.scitotenv.2020.141424 DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain Jordi Martorell-Marugán, Juan Antonio Villatoro-García, Adrián García-Moreno, Raúl López-Domínguez, Francisco Requena, Juan Julián Merelo, Marina Lacasaña, Juan de Dios Luna, Juan J. Díaz-Mochón, Jose A. Lorente, Pedro Carmona-Sáez Science of The Total Environment, Volume 750, 2021, 141424, ISSN 0048-9697
COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid
Sarah Heili-Frades, Pablo Minguez, Ignacio Mahillo Fernández, Tomás Prieto-Rumeau, [...], COVID FJD-TEAM
preprint  medRxiv
DOI: 10.1101/2020.05.22.20109850
There is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied. A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients. We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.
2020-05-29 2020 other preprint abstract-available data-available 10.1101/2020.05.22.20109850 COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid Sarah Heili-Frades, Pablo Minguez, Ignacio Mahillo Fernández, Tomás Prieto-Rumeau, Antonio Herrero González, Lorena de la Fuente, María Jesús Rodríguez Nieto, Germán Peces-Barba Romero, Mario Peces-Barba, María del Pilar Carballosa de Miguel, Itziar Fernández Ormaechea, Alba Naya prieto, Farah Ezzine de Blas, Luis Jiménez Hiscock, Cesar Perez Calvo, Arnoldo Santos, Luis Enrique Muñoz Alameda, Fredeswinda Romero Bueno, Miguel Górgolas Hernández-Mora, Alfonso Cabello Úbeda, Beatriz Álvarez Álvarez, Elizabet Petkova, Nerea Carrasco, Dolores Martín Ríos, Nicolás González Mangado, Olga Sánchez Pernaute, COVID FJD-TEAM medRxiv
COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms
Marek Ostaszewski, Alexander Mazein, Marc E. Gillespie, Inna Kuperstein, [...], Reinhard Schneider
Sci Data 7, 136 (2020)
DOI: 10.1038/s41597-020-0477-8
2020-05-05 2020 other article data-available 10.1038/s41597-020-0477-8 COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms Marek Ostaszewski, Alexander Mazein, Marc E. Gillespie, Inna Kuperstein, Anna Niarakis, Henning Hermjakob, Alexander R. Pico, Egon L. Willighagen, Chris T. Evelo, Jan Hasenauer, Falk Schreiber, Andreas Dräger, Emek Demir, Olaf Wolkenhauer, Laura I. Furlong, Emmanuel Barillot, Joaquin Dopazo, Aurelio Orta-Resendiz, Francesco Messina, Alfonso Valencia, Akira Funahashi, Hiroaki Kitano, Charles Auffray, Rudi Balling, Reinhard Schneider Sci Data 7, 136 (2020)
Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs,
Camila Pontes, Victoria Ruiz-Serra, Rosalba Lepore, Alfonso Valencia
Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 759-766, ISSN 2001-0370.
DOI: 10.1016/j.csbj.2021.01.006
The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the β-CoV spike protein family, using sequence information alone, can provide valuable insights on the molecular basis of the specificity of β-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptor adaptation of circulating and future novel β-CoVs.
2021-01-12 2021 other article abstract-available data-available 10.1016/j.csbj.2021.01.006 Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs, Camila Pontes, Victoria Ruiz-Serra, Rosalba Lepore, Alfonso Valencia Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 759-766, ISSN 2001-0370.
Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey.
Jordi Alonso, Gemma Vilagut, Philippe Mortier, Montse Ferrer, [...], MINDCOVID Working group (2020)
Revista de psiquiatria y salud mental, S1888-9891(20)30128-2. Advance online publication.
DOI: 10.1016/j.rpsm.2020.12.001
INTRODUCTION: Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. METHODS: All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surveys assessing individual characteristics, COVID-19 infection status and exposure, and mental health status (May 5 - September 7, 2020). We report: probable current mental disorders (Major Depressive Disorder-MDD- [PHQ-8≥10], Generalized Anxiety Disorder-GAD- [GAD-7≥10], Panic attacks, Posttraumatic Stress Disorder -PTSD- [PCL-5≥7]; and Substance Use Disorder -SUD-[CAGE-AID≥2]. Severe disability assessed by the Sheehan Disability Scale was used to identify probable "disabling" current mental disorders. RESULTS: 9,138 healthcare workers participated. Prevalence of screen-positive disorder: 28.1% MDD; 22.5% GAD, 24.0% Panic; 22.2% PTSD; and 6.2% SUD. Overall 45.7% presented any current and 14.5% any disabling current mental disorder. Workers with pre-pandemic lifetime mental disorders had almost twice the prevalence than those without. Adjusting for all other variables, odds of any disabling mental disorder were: prior lifetime disorders (TUS: OR=5.74; 95%CI 2.53-13.03; Mood: OR=3.23; 95%CI:2.27-4.60; Anxiety: OR=3.03; 95%CI:2.53-3.62); age category 18-29 years (OR=1.36; 95%CI:1.02-1.82), caring "all of the time" for COVID-19 patients (OR=5.19; 95%CI: 3.61-7.46), female gender (OR=1.58; 95%CI: 1.27-1.96) and having being in quarantine or isolated (OR= 1.60; 95CI:1.31-1.95). CONCLUSIONS: One in seven Spanish healthcare workers screened positive for a disabling mental disorder during the first wave of the COVID-19 pandemic. Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.
2020-12-20 2020 other article abstract-available data-available 10.1016/j.rpsm.2020.12.001 Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey. Jordi Alonso, Gemma Vilagut, Philippe Mortier, Montse Ferrer, Itxaso Alayo, Andrés Aragón-Peña, Enric Aragonès, Mireia Campos, Isabel D. Cura-González, José I. Emparanza, Meritxell Espuga, Maria João Forjaz, Ana González-Pinto, Josep M. Haro, Nieves López-Fresneña, Alma D. Martínez de Salázar, Juan D. Molina, Rafael M. Ortí-Lucas, Mara Parellada, José Maria Pelayo-Terán, Aurora Pérez-Zapata, José I. Pijoan, Nieves Plana, Maria Teresa Puig, Cristina Rius, Carmen Rodríguez-Blázquez, Ferran Sanz, Consol Serra, Ronald C. Kessler, Ronny Bruffaerts, Eduard Vieta, Víctor Pérez-Solà, MINDCOVID Working group (2020) Revista de psiquiatria y salud mental, S1888-9891(20)30128-2. Advance online publication.
COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms
Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, [...], the COVID-19 Disease Map Community
preprint  BioRxiv
DOI: 10.1101/2020.10.26.356014
We describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.
2021-02-16 2021 other preprint abstract-available data-available 10.1101/2020.10.26.356014 COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, Robert Phair, Aurelio Orta-Resendiz, Vidisha Singh, Sara Sadat Aghamiri, Marcio Luis Acencio, Enrico Glaab, Andreas Ruepp, Gisela Fobo, Corinna Montrone, Barbara Brauner, Goar Frishman, Luis Cristóbal Monraz Gómez, Julia Somers, Matti Hoch, Shailendra Kumar Gupta, Julia Scheel, Hanna Borlinghaus, Tobias Czauderna, Falk Schreiber, Arnau Montagud, Miguel Ponce de Leon, Akira Funahashi, Yusuke Hiki, Noriko Hiroi, Takahiro G. Yamada, Andreas Dräger, Alina Renz, Muhammad Naveez, Zsolt Bocskei, Francesco Messina, Daniela Börnigen, Liam Fergusson, Marta Conti, Marius Rameil, Vanessa Nakonecnij, Jakob Vanhoefer, Leonard Schmiester, Muying Wang, Emily E. Ackerman, Jason Shoemaker, Jeremy Zucker, Kristie Oxford, Jeremy Teuton, Ebru Kocakaya, Gökçe Yağmur Summak, Kristina Hanspers, Martina Kutmon, Susan Coort, Lars Eijssen, Friederike Ehrhart, D. A. B. Rex, Denise Slenter, Marvin Martens, Nhung Pham, Robin Haw, Bijay Jassal, Lisa Matthews, Marija Orlic-Milacic, Andrea Senff Ribeiro, Karen Rothfels, Veronica Shamovsky, Ralf Stephan, Cristoffer Sevilla, Thawfeek Varusai, Jean-Marie Ravel, Rupsha Fraser, Vera Ortseifen, Silvia Marchesi, Piotr Gawron, Ewa Smula, Laurent Heirendt, Venkata Satagopam, Guanming Wu, Anders Riutta, Martin Golebiewski, Stuart Owen, Carole Goble, Xiaoming Hu, Rupert W. Overall, Dieter Maier, Angela Bauch, Benjamin M. Gyori, John A. Bachman, Carlos Vega, Valentin Grouès, Miguel Vazquez, Pablo Porras, Luana Licata, Marta Iannuccelli, Francesca Sacco, Anastasia Nesterova, Anton Yuryev, Anita de Waard, Denes Turei, Augustin Luna, Ozgun Babur, Sylvain Soliman, Alberto Valdeolivas, Marina Esteban-Medina, Maria Peña-Chilet, Kinza Rian, Tomáš Helikar, Bhanwar Lal Puniya, Dezso Modos, Agatha Treveil, Marton Olbei, Bertrand De Meulder, Aurélien Dugourd, Aurélien Naldi, Vincent Noël, Laurence Calzone, Chris Sander, Emek Demir, Tamas Korcsmaros, Tom C. Freeman, Franck Augé, Jacques S. Beckmann, Jan Hasenauer, Olaf Wolkenhauer, Egon L. Wilighagen, Alexander R. Pico, Chris T. Evelo, Marc E. Gillespie, Lincoln D. Stein, Henning Hermjakob, Peter D’Eustachio, Julio Saez-Rodriguez, Joaquin Dopazo, Alfonso Valencia, Hiroaki Kitano, Emmanuel Barillot, Charles Auffray, Rudi Balling, Reinhard Schneider, the COVID-19 Disease Map Community BioRxiv
Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19
García-Escobar A, Vera-Vera S, Jurado-Román A, Jiménez-Valero S, [...], Moreno R.
Biomolecules. 2022; 12 (1)
DOI:
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that exists in two forms: the first is a transmembrane protein; the second is a soluble catalytic ectodomain of ACE2. The catalytic ectodomain of ACE2 undergoes shedding by a disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), in which calmodulin mediates the calcium signaling pathway that is involved in ACE2 release, resulting in a soluble catalytic ectodomain of ACE2 that can be measured as soluble ACE2 plasma activity. The shedding of the ACE2 catalytic ectodomain plays a role in cardiac remodeling and endothelial dysfunction and is a predictor of all-cause mortality, including cardiovascular mortality. Moreover, considerable evidence supports that the ACE2 catalytic ectodomain is an essential entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Additionally, endotoxins and the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-alpha (TNFα) all enhanced soluble catalytic ectodomain ACE2 shedding from the airway epithelia, suggesting that the shedding of ACE2 may represent a mechanism by which viral entry and infection may be controlled such as some types of betacoronavirus. In this regard, ACE2 plays an important role in inflammation and thrombotic response, and its down-regulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury. Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. Furthermore, given that vitamin D enhanced the shedding of ACE2, some studies reported that vitamin D treatment is associated with prognosis improvement in COVID-19. This is an updated review on the evidence, clinical, and therapeutic applications of ACE2 for COVID-19.
2022-01-01 2022 other review-article; Review; Journal Article abstract-available Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19 García-Escobar A, Vera-Vera S, Jurado-Román A, Jiménez-Valero S, Galeote G, Moreno R. Biomolecules. 2022; 12 (1)
Entrectinib-A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells.
Peralta-Garcia A, Torrens-Fontanals M, Stepniewski TM, Grau-Expósito J, [...], Selent J.
Int J Mol Sci. 2021; 22 (24)
DOI: 10.3390/ijms222413592
Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.
2021-12-18 2021 other research-article; Journal Article abstract-available 10.3390/ijms222413592 Entrectinib-A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells. Peralta-Garcia A, Torrens-Fontanals M, Stepniewski TM, Grau-Expósito J, Perea D, Ayinampudi V, Waldhoer M, Zimmermann M, Buzón MJ, Genescà M, Selent J. Int J Mol Sci. 2021; 22 (24)
Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19.
Hmadcha A, Soria B, Zhao RC, Smani T, [...], Valverde I.
Front Cell Dev Biol. 2021; 9
DOI: 10.3389/fcell.2021.813384
2021-12-14 2021 other Editorial 10.3389/fcell.2021.813384 Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19. Hmadcha A, Soria B, Zhao RC, Smani T, Valverde I. Front Cell Dev Biol. 2021; 9
Advances and gaps in SARS-CoV-2 infection models.
Muñoz-Fontela C, Widerspick L, Albrecht RA, Beer M, [...], Barouch DH.
PLoS Pathog. 2022; 18 (1)
DOI: 10.1371/journal.ppat.1010161
The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available 10.1371/journal.ppat.1010161 Advances and gaps in SARS-CoV-2 infection models. Muñoz-Fontela C, Widerspick L, Albrecht RA, Beer M, Carroll MW, de Wit E, Diamond MS, Dowling WE, Funnell SGP, García-Sastre A, Gerhards NM, de Jong R, Munster VJ, Neyts J, Perlman S, Reed DS, Richt JA, Riveros-Balta X, Roy CJ, Salguero FJ, Schotsaert M, Schwartz LM, Seder RA, Segalés J, Vasan SS, Henao-Restrepo AM, Barouch DH. PLoS Pathog. 2022; 18 (1)
Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges.
Masterson CH, Ceccato A, Artigas A, Dos Santos C, [...], Laffey JG.
Intensive Care Med Exp. 2021; 9 (1)
DOI: 10.1186/s40635-021-00424-5
Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
2021-12-31 2021 other review-article; Review; Journal Article abstract-available 10.1186/s40635-021-00424-5 Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges. Masterson CH, Ceccato A, Artigas A, Dos Santos C, Rocco PR, Rolandsson Enes S, Weiss DJ, McAuley D, Matthay MA, English K, Curley GF, Laffey JG. Intensive Care Med Exp. 2021; 9 (1)
Impact of COVID-19 on liver disease: From the experimental to the clinic perspective.
Gato S, Lucena-Valera A, Muñoz-Hernández R, Sousa JM, [...], Ampuero J.
World J Virol. 2021; 10 (6)
DOI: 10.5501/wjv.v10.i6.301
Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.
2021-11-01 2021 other review-article; Review; Journal Article abstract-available 10.5501/wjv.v10.i6.301 Impact of COVID-19 on liver disease: From the experimental to the clinic perspective. Gato S, Lucena-Valera A, Muñoz-Hernández R, Sousa JM, Romero-Gómez M, Ampuero J. World J Virol. 2021; 10 (6)
SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications.
Sharun K, Dhama K, Pawde AM, Gortázar C, [...], Attia YA.
Vet Q. 2021; 41 (1)
DOI: 10.1080/01652176.2021.1921311
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously 2019-nCoV) is suspected of having originated in 2019 in China from a coronavirus infected bat of the genus Rhinolophus. Following the initial emergence, possibly facilitated by a mammalian bridge host, SARS-CoV-2 is currently transmitted across the globe via efficient human-to-human transmission. Results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters are susceptible to SARS-CoV-2 infection, and that cat-to-cat and ferret-to-ferret transmission can take place via contact and air. However, natural infections of SARS-CoV-2 have been reported only in pet dogs and cats, tigers, lions, snow leopards, pumas, and gorillas at zoos, and farmed mink and ferrets. Even though human-to-animal spillover has been reported at several instances, SARS-CoV-2 transmission from animals-to-humans has only been reported from mink-to-humans in mink farms. Following the rapid transmission of SARS-CoV-2 within the mink population, a new mink-associated SARS-CoV-2 variant emerged that was identified in both humans and mink. The increasing reports of SARS-CoV-2 in carnivores indicate the higher susceptibility of animal species belonging to this order. The sporadic reports of SARS-CoV-2 infection in domestic and wild animal species require further investigation to determine if SARS-CoV-2 or related Betacoronaviruses can get established in kept, feral or wild animal populations, which may eventually act as viral reservoirs. This review analyzes the current evidence of SARS-CoV-2 natural infection in domestic and wild animal species and their possible implications on public health.
2021-12-01 2021 other review-article; Review; Journal Article abstract-available 10.1080/01652176.2021.1921311 SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications. Sharun K, Dhama K, Pawde AM, Gortázar C, Tiwari R, Tiwari R, Bonilla-Aldana DK, Rodriguez-Morales AJ, de la Fuente J, Michalak I, Attia YA. Vet Q. 2021; 41 (1)
Reinfection by SARS-CoV-2: The first one in a family reported in Spain.
Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C.
Med Clin (Engl Ed). 2021; 157 (9)
DOI: 10.1016/j.medcle.2021.04.010
2021-11-05 2021 other letter; Journal Article 10.1016/j.medcle.2021.04.010 Reinfection by SARS-CoV-2: The first one in a family reported in Spain. Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C. Med Clin (Engl Ed). 2021; 157 (9)
SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients.
Gutiérrez-Chamorro L, Riveira-Muñoz E, Barrios C, Palau V, [...], Ballana E.
Viruses. 2021; 13 (9)
DOI: 10.3390/v13091715
Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with ACE2 gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.
2021-08-28 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13091715 SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients. Gutiérrez-Chamorro L, Riveira-Muñoz E, Barrios C, Palau V, Nevot M, Pedreño-López S, Senserrich J, Massanella M, Clotet B, Cabrera C, Mitjà O, Crespo M, Pascual J, Riera M, Ballana E. Viruses. 2021; 13 (9)
Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research.
Caronna E, Pozo-Rosich P.
Curr Pain Headache Rep. 2021; 25 (11)
DOI: 10.1007/s11916-021-00987-8

Purpose of review

Headache is a common symptom of COVID-19 with emerging literature being published on the subject. Although it may seem unspecific, scientific evidence has allowed a better definition of this headache type, revealing relevant associations with other COVID-19 symptoms and prognoses. We therefore sought to highlight the most remarkable findings concerning headache secondary to COVID-19, specifically focusing on epidemiology, characteristics, pathophysiology, and treatments.

Recent findings

The real prevalence of headache as a symptom of COVID-19 is still unclear ranging from 10 to 70%. Headache mainly has a tension-type-like phenotype, although 25% of individuals present with migraine-like features that also occur in patients without personal migraine history. This finding suggests that a likely pathophysiological mechanism is the activation of the trigeminovascular system. SARS-CoV-2 neurotropism can occur by trans-synaptic invasion through the olfactory route from the nasal cavity, leading to anosmia which has been associated with headache. SARS-CoV-2 protein has been found not only in olfactory mucosa and bulbs but also in trigeminal branches and the trigeminal ganglion, supporting this hypothesis. However, other mechanisms such as brain vessels inflammation due to SARS-CoV-2 damage to the endothelium or systemic inflammation in the context of cytokine storm cannot be ruled out. Interestingly, headache has been associated with lower COVID-19 mortality. No specific treatment for COVID-19 headache is available at present. Studies show that investigating COVID-19 headache represents an opportunity not only to better understand COVID-19 in general but also to advance in the knowledge of both secondary and primary headaches. Future research is therefore warranted.
2021-11-11 2021 other review-article; Review; Journal Article abstract-available 10.1007/s11916-021-00987-8 Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research. Caronna E, Pozo-Rosich P. Curr Pain Headache Rep. 2021; 25 (11)
Dental Healthcare Amid the COVID-19 Pandemic.
Butt RT, Janjua OS, Qureshi SM, Shaikh MS, [...], Zafar MS.
Int J Environ Res Public Health. 2021; 18 (21)
DOI: 10.3390/ijerph182111008
The hustle and bustle of the planet Earth have come to a halt thanks to the novel coronavirus. The virus has affected approximately 219 million people globally; taken the lives of 4.55 million patients as of September 2021; and created an ambiance of fear, social distancing, and economic instability. The purpose of this review article is to trace the historical origin and evolution of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). The virus is highly contagious with a unique feature of rapid mutations-the scientific research is paving the way for discoveries regarding novel coronavirus disease (COVID-19) diagnosis, features, prevention, and vaccination. The connections between the coronavirus pandemic and dental practices are essential because COVID-19 is transmitted by aerosols, fomites, and respiratory droplets, which are also produced during dental procedures, putting both the patient and the dentist at risk. The main emphasis of this paper is to highlight the psychological, economic, and social impact of this pandemic on dental practices throughout the world and under what circumstances and guidelines can dental health care be provided. In the current situation of the pandemic, an appropriate screening tool must be established either by using rapid molecular testing or saliva point-of-care technology, which will be effective in identifying as well as isolating the potential contacts and carriers in hopes to contain and mitigate infection. The blessing in disguise is that this virus has united the leaders, scientists, health care providers, and people of all professions from all around the world to fight against a common enemy.
2021-10-20 2021 other review-article; Review; Journal Article abstract-available 10.3390/ijerph182111008 Dental Healthcare Amid the COVID-19 Pandemic. Butt RT, Janjua OS, Qureshi SM, Shaikh MS, Guerrero-Gironés J, Rodríguez-Lozano FJ, Zafar MS. Int J Environ Res Public Health. 2021; 18 (21)
First Detection of SARS-CoV-2 Delta (B.1.617.2) Variant of Concern in a Dog with Clinical Signs in Spain.
Fernández-Bastit L, Rodon J, Pradenas E, Marfil S, [...], Segalés J.
Viruses. 2021; 13 (12)
DOI: 10.3390/v13122526
Several cases of naturally infected dogs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported despite the apparently low susceptibility of this species. Here, we document the first reported case of infection caused by the Delta (B.1.617.2) variant of concern (VOC) in a dog in Spain that lived with several household members suffering from Coronavirus Infectious Disease 2019 (COVID-19). The animal displayed mild digestive and respiratory clinical signs and had a low viral load in the oropharyngeal swab collected at the first sampling. Whole-genome sequencing indicated infection with the Delta variant, coinciding with the predominant variant during the fifth pandemic wave in Spain. The dog seroconverted, as detected 21 days after the first sampling, and developed neutralizing antibodies that cross-neutralized different SARS-CoV-2 variants. This study further emphasizes the importance of studying the susceptibility of animal species to different VOCs and their potential role as reservoirs in the context of COVID-19.
2021-12-16 2021 other Research Support, Non-U.S. Gov't; Case Reports; case-report abstract-available 10.3390/v13122526 First Detection of SARS-CoV-2 Delta (B.1.617.2) Variant of Concern in a Dog with Clinical Signs in Spain. Fernández-Bastit L, Rodon J, Pradenas E, Marfil S, Trinité B, Parera M, Roca N, Pou A, Cantero G, Lorca-Oró C, Carrillo J, Izquierdo-Useros N, Clotet B, Noguera-Julián M, Blanco J, Vergara-Alert J, Segalés J. Viruses. 2021; 13 (12)
Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19).
Tizaoui K, Zidi I, Lee KH, Ghayda RA, [...], Shin JI.
Int J Biol Sci. 2020; 16 (15)
DOI: 10.7150/ijbs.48812
In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11th March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.
2020-09-12 2020 other review-article; Review; Journal Article abstract-available 10.7150/ijbs.48812 Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19). Tizaoui K, Zidi I, Lee KH, Ghayda RA, Hong SH, Li H, Smith L, Koyanagi A, Jacob L, Kronbichler A, Shin JI. Int J Biol Sci. 2020; 16 (15)
Molecular Interactions of SARS-CoV-2 in Lung Tissue of Patients with Chronic Obstructive Pulmonary Disease.
Agusti A, Sibila O, Casas-Recasens S, Mendoza N, [...], Faner R.
Ann Am Thorac Soc. 2021; 18 (11)
DOI: 10.1513/annalsats.202006-619rl
2021-11-01 2021 other Letter 10.1513/annalsats.202006-619rl Molecular Interactions of SARS-CoV-2 in Lung Tissue of Patients with Chronic Obstructive Pulmonary Disease. Agusti A, Sibila O, Casas-Recasens S, Mendoza N, Perea L, Lopez-Giraldo A, Faner R. Ann Am Thorac Soc. 2021; 18 (11)
Narrative review on clinical considerations for patients with diabetes and COVID-19: More questions than answers.
Katsiki N, Gómez-Huelgas R, Mikhailidis DP, Pérez-Martínez P.
Int J Clin Pract. 2021; 75 (11)
DOI: 10.1111/ijcp.14833

Background-aim

Diabetes, obesity and hypertension are common comorbidities associated with increased severity and mortality rates from Corona Virus Disease (COVID)-19.

Methods

In this narrative review (using the PubMed database), we discuss epidemiological data and pathophysiological links between diabetes and COVID-19. The potential effects of glycaemic control and antidiabetic drugs on the prevalence and outcomes of COVID-19 are also reviewed, as well as the role of telemedicine and diabetes self-management in the post-COVID-19 era.

Results

Diabetes has been linked to COVID-19 morbidity and mortality, although further research is needed to elucidate this association. In the meantime, physicians should be aware of the potential rise in the prevalence of diabetes (due to unhealthy lifestyle changes during the pandemic), its severity and complications and focus on achieving optimal diabetes prevention and management. Telemedicine and diabetes self-management may help towards this direction. Dipeptidyl-peptidase 4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors may affect viral entry and infection, and thus COVID-19 outcomes, as shown in observational studies.

Conclusion

Diabetes has been associated with COVID-19 development and progression. Certain antidiabetic drugs may influence COVID-19 prevention and management. The results of ongoing randomized clinical trials will shed more light on this field.
2021-09-21 2021 other review-article; Review; Journal Article abstract-available 10.1111/ijcp.14833 Narrative review on clinical considerations for patients with diabetes and COVID-19: More questions than answers. Katsiki N, Gómez-Huelgas R, Mikhailidis DP, Pérez-Martínez P. Int J Clin Pract. 2021; 75 (11)
SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.
Queirós-Reis L, Gomes da Silva P, Gonçalves J, Brancale A, [...], Mesquita JR.
Int J Mol Sci. 2021; 22 (19)
DOI: 10.3390/ijms221910836
Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.
2021-10-07 2021 other review-article; Review; Journal Article abstract-available 10.3390/ijms221910836 SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response. Queirós-Reis L, Gomes da Silva P, Gonçalves J, Brancale A, Bassetto M, Mesquita JR. Int J Mol Sci. 2021; 22 (19)
Mapping the intellectual structure of the coronavirus field (2000-2020): a co-word analysis.
Pourhatami A, Kaviyani-Charati M, Kargar B, Baziyad H, [...], Olmeda-Gómez C.
Scientometrics. 2021;
DOI: 10.1007/s11192-021-04038-2
Over the two last decades, coronaviruses have affected human life in different ways, especially in terms of health and economy. Due to the profound effects of novel coronaviruses, growing tides of research are emerging in various research fields. This paper employs a co-word analysis approach to map the intellectual structure of the coronavirus literature for a better understanding of how coronavirus research and the disease itself have developed during the target timeframe. A strategic diagram has been drawn to depict the coronavirus domain's structure and development. A detailed picture of coronavirus literature has been extracted from a huge number of papers to provide a quick overview of the coronavirus literature. The main themes of past coronavirus-related publications are (a) "Antibody-Virus Interactions," (b) "Emerging Infectious Diseases," (c) "Protein Structure-based Drug Design and Antiviral Drug Discovery," (d) "Coronavirus Detection Methods," (e) "Viral Pathogenesis and Immunity," and (f) "Animal Coronaviruses." The emerging infectious diseases are mostly related to fatal diseases (such as Middle East respiratory syndrome, severe acute respiratory syndrome, and COVID-19) and animal coronaviruses (including porcine, turkey, feline, canine, equine, and bovine coronaviruses and infectious bronchitis virus), which are capable of placing animal-dependent industries such as the swine and poultry industries under strong economic pressure. Although considerable research into coronavirus has been done, this unique field has not yet matured sufficiently. Therefore, "Antibody-virus Interactions," "Emerging Infectious Diseases," and "Coronavirus Detection Methods" hold interesting, promising research gaps to be both explored and filled in the future.
2021-06-15 2021 other research-article; Journal Article abstract-available 10.1007/s11192-021-04038-2 Mapping the intellectual structure of the coronavirus field (2000-2020): a co-word analysis. Pourhatami A, Kaviyani-Charati M, Kargar B, Baziyad H, Kargar M, Olmeda-Gómez C. Scientometrics. 2021;
Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019.
Roldán-Santiago E, Benito-Berlinches A, Martínez-García L, Quereda C, [...], Pérez-Elías MJ.
Clin Infect Dis. 2021; 73 (11)
DOI: 10.1093/cid/ciaa1422
A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.
2021-12-01 2021 other brief-report; Journal Article abstract-available 10.1093/cid/ciaa1422 Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019. Roldán-Santiago E, Benito-Berlinches A, Martínez-García L, Quereda C, Rodríguez-Martín E, Pérez-Elías P, López-Pintor JM, Walo-Delgado PE, Moreno-Zamora A, Fernández-Velasco JI, García-Abellás P, Ballester-González R, Villar LM, Pérez-Elías MJ. Clin Infect Dis. 2021; 73 (11)
Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians.
Chee J, Loh WS, Liu Z, Mullol J, [...], Wang Y.
Curr Allergy Asthma Rep. 2021; 21 (6)
DOI: 10.1007/s11882-021-01015-w

Purpose of review

Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease.

Recent findings

ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.
2021-07-14 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1007/s11882-021-01015-w Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians. Chee J, Loh WS, Liu Z, Mullol J, Wang Y. Curr Allergy Asthma Rep. 2021; 21 (6)
Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19.
Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, [...], Resino S.
J Infect. 2021;
DOI: 10.1016/j.jinf.2021.11.002
2021-11-06 2021 other Letter 10.1016/j.jinf.2021.11.002 Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19. Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, Micán R, Pérez-Elías MJ, García-Fraile LJ, Peraire J, Suárez-García I, Jiménez-Sousa MÁ, Fernández-Rodríguez A, Vázquez M, Ryan P, González-García J, Jarrín I, Mas V, Martínez I, Resino S. J Infect. 2021;
Cardiopulmonary resuscitation during the COVID-19 pandemic in Spain.
Aliaño Piña M, Ruiz Villén C, Galán Serrano J, Monedero Rodríguez P.
Rev Esp Anestesiol Reanim (Engl Ed). 2021; 68 (8)
DOI: 10.1016/j.redare.2021.09.001

Objectives

The disease COVID-19 produces serious complications that can lead to cardiorespiratory arrest. Quality cardiopulmonary resuscitation (CPR) can improve patient prognosis. The objective of this study is to evaluate the performance of the specialty of Anesthesiology in the management of CPR during the pandemic.

Methods

A survey was carried out with Google Forms consisting of 19 questions. The access link to the questionnaire was sent by email by the Spanish Society of Anesthesia (SEDAR) to all its members.

Results

225 responses were obtained. The regions with the highest participation were: Madrid, Catalonia, Valencia and Andalusia. 68.6%% of the participants work in public hospitals. 32% of the participants habitually work in intensive care units (ICU), however, 62.1% have attended critical COVID-19 in the ICU and 72.6% have anesthetized them in the operating room. 26,3% have attended some cardiac arrest, 16,8% of the participants admitted to lead the manoeuvres, 16,8% detailed that it had been another department, and 66,2% was part of the team, but did not lead the assistance. Most of the CPR was performed in supine, only 5% was done in prone position. 54.6% of participants had not taken any course of Advance Life Support (ALS) in the last 2 years. 97.7% of respondents think that Anesthesia should lead the in-hospital CPR.

Conclusion

The specialty of Anesthesiology has actively participated in the care of the critically ill patient and in the management of CPR during the COVID-19 pandemic. However, training and/or updating in ALS is required.
2021-09-15 2021 other research-article; Journal Article abstract-available 10.1016/j.redare.2021.09.001 Cardiopulmonary resuscitation during the COVID-19 pandemic in Spain. Aliaño Piña M, Ruiz Villén C, Galán Serrano J, Monedero Rodríguez P. Rev Esp Anestesiol Reanim (Engl Ed). 2021; 68 (8)
Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses.
Aparicio B, Casares N, Egea J, Ruiz M, [...], Sarobe P.
Emerg Microbes Infect. 2021; 10 (1)
DOI: 10.1080/22221751.2021.1978823
Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p <0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p <0.01 and p <0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1080/22221751.2021.1978823 Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses. Aparicio B, Casares N, Egea J, Ruiz M, Llopiz D, Maestro S, Olagüe C, González-Aseguinolaza G, Smerdou C, López-Díaz de Cerio A, Inogés S, Prósper F, Yuste JR, Carmona-Torre F, Reina G, Lasarte JJ, Sarobe P. Emerg Microbes Infect. 2021; 10 (1)
Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience.
F S, Haji K E, Vidal-Balle A, J B.
Brain Behav Immun Health. 2021;
DOI: 10.1016/j.bbih.2021.100399
Due to the infection by the SARS-CoV-2 virus (COVID-19) there were also reported neurological symptoms, being the most frequent and best cited those that affect the cerebrovascular, sensorial, cognitive and motor functions, together with the neurological diffuse symptoms as for examples headache or dizziness. Besides, some of them behave high risk of mortality. Consequently, it is crucial to elucidate the mechanisms of action in brain of SARS-CoV-2 virus in order to create new therapeutic targets to fight against this new disease. Since now the mechanisms of arrival to the brain seems to be related with the following processes: blood brain barrier (BBB) disruption together with nervous or axonal transport of the virus by the trigeminal nerve, the vagus nerve, or the brain-gut-axis. Being two the mechanisms of brain affectation most cited: a direct affectation of the virus in the brain through neuroinvasion and an indirect mechanism of action due to the effects of the systemic infection. Both processes include the triggering of inflammation, hypoxia and the increased likelihood of secondary infections. This topic supposes a major novel challenge for neuroscience. Therefore, the aim of this review is to provide summarized information about the neurological symptomatology and the brain pathogenic mechanisms involved and reported in COVID-19.
2021-11-30 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.bbih.2021.100399 Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience. F S, Haji K E, Vidal-Balle A, J B. Brain Behav Immun Health. 2021;
Anti-SARS-CoV-2 hyperimmune globulin demonstrates potent neutralization and antibody-dependent cellular cytotoxicity and phagocytosis through N and S proteins.
Díez JM, Romero C, Cruz M, Vandeberg P, [...], Gajardo R.
J Infect Dis. 2021;
DOI: 10.1093/infdis/jiab540

Background

Although COVID-19 vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need.

Methods

Functional characterization of anti-SARS-CoV-2 hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus induced cytotoxicity, TCID50 reduction and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA (1), Italy (1), Spain (2): 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1 and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated.

Results

All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all four methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. hIG induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins.

Conclusions

Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.
2021-10-25 2021 other research-article; Journal Article abstract-available 10.1093/infdis/jiab540 Anti-SARS-CoV-2 hyperimmune globulin demonstrates potent neutralization and antibody-dependent cellular cytotoxicity and phagocytosis through N and S proteins. Díez JM, Romero C, Cruz M, Vandeberg P, Merritt WK, Pradenas E, Trinité B, Blanco J, Clotet B, Willis T, Gajardo R. J Infect Dis. 2021;
Aptamer Sandwich Assay for the Detection of SARS-CoV-2 Spike Protein Antigen.
Svobodova M, Skouridou V, Jauset-Rubio M, Viéitez I, [...], O'Sullivan CK.
ACS Omega. 2021; 6 (51)
DOI: 10.1021/acsomega.1c05521
The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged at the end of 2019, resulting in the ongoing COVID-19 pandemic. The high transmissibility of the virus and the substantial number of asymptomatic individuals have led to an exponential rise in infections worldwide, urgently requiring global containment strategies. Reverse transcription-polymerase chain reaction is the gold standard for the detection of SARS-CoV-2 infections. Antigen tests, targeting the spike (S) or nucleocapsid (N) viral proteins, are considered as complementary tools. Despite their shortcomings in terms of sensitivity and specificity, antigen tests could be deployed for the detection of potentially contagious individuals with high viral loads. In this work, we sought to develop a sandwich aptamer-based assay for the detection of the S protein of SARS-CoV-2. A detailed study on the binding properties of aptamers to the receptor-binding domain of the S protein in search of aptamer pairs forming a sandwich is presented. Screening of aptamer pairs and optimization of assay conditions led to the development of a laboratory-based sandwich assay able to detect 21 ng/mL (270 pM) of the protein with negligible cross-reactivity with the other known human coronaviruses. The detection of 375 pg of the protein in viral transport medium demonstrates the compatibility of the assay with clinical specimens. Finally, successful detection of the S antigen in nasopharyngeal swab samples collected from suspected patients further establishes the suitability of the assay for screening purposes as a complementary tool to assist in the control of the pandemic.
2021-12-15 2021 fondo-covid research-article; Journal Article abstract-available 10.1021/acsomega.1c05521 Aptamer Sandwich Assay for the Detection of SARS-CoV-2 Spike Protein Antigen. Svobodova M, Skouridou V, Jauset-Rubio M, Viéitez I, Fernández-Villar A, Cabrera Alvargonzalez JJ, Poveda E, Bofill CB, Sans T, Bashammakh A, Alyoubi AO, O'Sullivan CK. ACS Omega. 2021; 6 (51)
Searching PubMed to Retrieve Publications on the COVID-19 Pandemic: Comparative Analysis of Search Strings.
Lazarus JV, Palayew A, Rasmussen LN, Andersen TH, [...], Norgaard O.
J Med Internet Res. 2020; 22 (11)
DOI: 10.2196/23449

Background

Since it was declared a pandemic on March 11, 2020, COVID-19 has dominated headlines around the world and researchers have generated thousands of scientific articles about the disease. The fast speed of publication has challenged researchers and other stakeholders to keep up with the volume of published articles. To search the literature effectively, researchers use databases such as PubMed.

Objective

The aim of this study is to evaluate the performance of different searches for COVID-19 records in PubMed and to assess the complexity of searches required.

Methods

We tested PubMed searches for COVID-19 to identify which search string performed best according to standard metrics (sensitivity, precision, and F-score). We evaluated the performance of 8 different searches in PubMed during the first 10 weeks of the COVID-19 pandemic to investigate how complex a search string is needed. We also tested omitting hyphens and space characters as well as applying quotation marks.

Results

The two most comprehensive search strings combining several free-text and indexed search terms performed best in terms of sensitivity (98.4%/98.7%) and F-score (96.5%/95.7%), but the single-term search COVID-19 performed best in terms of precision (95.3%) and well in terms of sensitivity (94.4%) and F-score (94.8%). The term Wuhan virus performed the worst: 7.7% for sensitivity, 78.1% for precision, and 14.0% for F-score. We found that deleting a hyphen or space character could omit a substantial number of records, especially when searching with SARS-CoV-2 as a single term.

Conclusions

Comprehensive search strings combining free-text and indexed search terms performed better than single-term searches in PubMed, but not by a large margin compared to the single term COVID-19. For everyday searches, certain single-term searches that are entered correctly are probably sufficient, whereas more comprehensive searches should be used for systematic reviews. Still, we suggest additional measures that the US National Library of Medicine could take to support all PubMed users in searching the COVID-19 literature.
2020-11-26 2020 other research-article; Journal Article abstract-available 10.2196/23449 Searching PubMed to Retrieve Publications on the COVID-19 Pandemic: Comparative Analysis of Search Strings. Lazarus JV, Palayew A, Rasmussen LN, Andersen TH, Nicholson J, Norgaard O. J Med Internet Res. 2020; 22 (11)
The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak.
Lauxmann MA, Santucci NE, Autrán-Gómez AM.
Int Braz J Urol. 2020; 46 (suppl.1)
DOI: 10.1590/s1677-5538.ibju.2020.s101
The SARS-CoV-2, a newly identified β-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.
2020-07-01 2020 other review-article; Review; Journal Article abstract-available 10.1590/s1677-5538.ibju.2020.s101 The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Lauxmann MA, Santucci NE, Autrán-Gómez AM. Int Braz J Urol. 2020; 46 (suppl.1)
SCoV2-MD: a database for the dynamics of the SARS-CoV-2 proteome and variant impact predictions.
Torrens-Fontanals M, Peralta-García A, Talarico C, Guixà-González R, [...], Selent J.
Nucleic Acids Res. 2022; 50 (D1)
DOI: 10.1093/nar/gkab977
SCoV2-MD (www.scov2-md.org) is a new online resource that systematically organizes atomistic simulations of the SARS-CoV-2 proteome. The database includes simulations produced by leading groups using molecular dynamics (MD) methods to investigate the structure-dynamics-function relationships of viral proteins. SCoV2-MD cross-references the molecular data with the pandemic evolution by tracking all available variants sequenced during the pandemic and deposited in the GISAID resource. SCoV2-MD enables the interactive analysis of the deposited trajectories through a web interface, which enables users to search by viral protein, isolate, phylogenetic attributes, or specific point mutation. Each mutation can then be analyzed interactively combining static (e.g. a variety of amino acid substitution penalties) and dynamic (time-dependent data derived from the dynamics of the local geometry) scores. Dynamic scores can be computed on the basis of nine non-covalent interaction types, including steric properties, solvent accessibility, hydrogen bonding, and other types of chemical interactions. Where available, experimental data such as antibody escape and change in binding affinities from deep mutational scanning experiments are also made available. All metrics can be combined to build predefined or custom scores to interrogate the impact of evolving variants on protein structure and function.
2022-01-01 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/nar/gkab977 SCoV2-MD: a database for the dynamics of the SARS-CoV-2 proteome and variant impact predictions. Torrens-Fontanals M, Peralta-García A, Talarico C, Guixà-González R, Giorgino T, Selent J. Nucleic Acids Res. 2022; 50 (D1)
Lipid peroxidation as a hallmark of severity in COVID-19 patients.
Martín-Fernández M, Aller R, Heredia-Rodríguez M, Gómez-Sánchez E, [...], Tamayo-Velasco Á.
Redox Biol. 2021; 48
DOI: 10.1016/j.redox.2021.102181

Background

Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease.

Methods

Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test.

Results

Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules' levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 μM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10-5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 μM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p < 0.001).

Conclusion

These findings deepen our knowledge of oxidative stress status in SARS-CoV-2 infection, supporting its important role in COVID-19. In fact, higher lipid peroxidation levels are independently associated to a higher risk of intubation or death at 28 days in COVID-19 patients.
2021-11-06 2021 other research-article; Journal Article abstract-available 10.1016/j.redox.2021.102181 Lipid peroxidation as a hallmark of severity in COVID-19 patients. Martín-Fernández M, Aller R, Heredia-Rodríguez M, Gómez-Sánchez E, Martínez-Paz P, Gonzalo-Benito H, Sánchez-de Prada L, Gorgojo Ó, Carnicero-Frutos I, Tamayo E, Tamayo-Velasco Á. Redox Biol. 2021; 48
Facts and Challenges about Asthma and COVID-19 among the Paediatric Population: A Systematic Literature Review.
Moreno-Sánchez E, Castillo-Viera E, Vélez-Moreno E, Gago-Valiente FJ.
Medicina (Kaunas). 2021; 57 (12)
DOI: 10.3390/medicina57121306
A systematic review of the literature was conducted to analyse the factors that affect the probability of the paediatric asthma population suffering from COVID-19 or SARS-CoV-2, such as asthma phenotypes, inhaled corticosteroids, and the effects of lockdown. This systematic review was based on PRISMA guidelines. A bibliographic search was conducted using BNE, BVS (LILAC), CSIC (IME, ISOC), IBECS, Scielo, Scopus, Medline, and PubMed, using the following search profile: (COVID-19 or 2019-NCOV or SARS-CoV-2 or COV-19) AND asthma AND (children or adolescents or youths or children or teenagers). The results were limited to those articles published between December 2019 and December 2020, selecting only articles published in Spanish, English and French that included the study population (children aged 0-18 years). Among the 1066 results of the bibliographic search and seven articles selected from a manual search, only 19 articles were found to fit our eligibility criteria. Most of the articles highlight the effects of lockdown on the paediatric asthma population, increased therapeutic compliance, and the role of inhaled corticosteroids and intrinsic factors such as ACE2 receptors as causes of the decreased prevalence of COVID-19 among the paediatric asthma population. This population has unique characteristics that serve as protective factors against COVID-19. The safety measures implemented during the lockdown period along with inhaled corticosteroid treatment also contributed to this protection.
2021-11-29 2021 other Systematic Review; review-article; Review; Journal Article abstract-available 10.3390/medicina57121306 Facts and Challenges about Asthma and COVID-19 among the Paediatric Population: A Systematic Literature Review. Moreno-Sánchez E, Castillo-Viera E, Vélez-Moreno E, Gago-Valiente FJ. Medicina (Kaunas). 2021; 57 (12)
Should we discount the laboratory origin of COVID-19?
Segreto R, Deigin Y, McCairn K, Sousa A, [...], Zhang D.
Environ Chem Lett. 2021;
DOI: 10.1007/s10311-021-01211-0
2021-03-25 2021 other Editorial 10.1007/s10311-021-01211-0 Should we discount the laboratory origin of COVID-19? Segreto R, Deigin Y, McCairn K, Sousa A, Sirotkin D, Sirotkin K, Couey JJ, Jones A, Zhang D. Environ Chem Lett. 2021;
"Five Keys to Safer Food" and COVID-19.
San Onofre N, Soler C, Merino-Torres JF, Soriano JM.
Nutrients. 2021; 13 (12)
DOI: 10.3390/nu13124491
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) and, up to 18:37 a.m. on 9 December 2021, it has produced 268,440,530 cases and 5,299,511 deaths. This disease, in some patients, included pneumonia and shortness of breath, being transmitted through droplets and aerosols. To date, there is no scientific literature to justify transmission directly from foods. In this review, we applied the precautionary principle for the home and the food industry using the known "Five Keys to Safer Food" manual developed by the World Health Organization (WHO) and extended punctually in its core information from five keys, in the light of new COVID-19 evidence, to guarantee a possible food safety tool.
2021-12-15 2021 other review-article; Review; Journal Article abstract-available 10.3390/nu13124491 "Five Keys to Safer Food" and COVID-19. San Onofre N, Soler C, Merino-Torres JF, Soriano JM. Nutrients. 2021; 13 (12)
Could Statin Therapy Be Useful in Patients With Coronavirus Disease 2019 (COVID-19)?
Torres-Peña JD, Katsiki N, Perez-Martinez P.
Front Cardiovasc Med. 2021; 8
DOI: 10.3389/fcvm.2021.775749
Acute respiratory distress syndrome (ARDS), resulting from an exaggerated inflammatory response, is the main cause of death from the coronavirus disease 2019 (COVID-19). Apart from respiratory infection, COVID-19 patients can develop cardiovascular disorders such as myocardial injury and myocarditis, pericarditis, cardiac arrest and arrhythmias, cardiomyopathy, heart failure, coagulation abnormalities and thrombosis. Statins can beneficially affect inflammation, oxidative stress, coagulation, thrombosis, angiotensin converting enzyme receptor, lipid rafts, and endothelial function. In this narrative review, we provide a critical overview of the current evidence and future perspectives on the use of statins to modulate the severity, duration and complications of COVID-19 through their pleiotropic properties.
2021-10-27 2021 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2021.775749 Could Statin Therapy Be Useful in Patients With Coronavirus Disease 2019 (COVID-19)? Torres-Peña JD, Katsiki N, Perez-Martinez P. Front Cardiovasc Med. 2021; 8
Explorative assessment of coronavirus-like short sequences from host-associated and environmental metagenomes.
Mora M, Wicaksono WA, Egamberdieva D, Krause R, [...], Berg G.
Sci Total Environ. 2021; 793
DOI: 10.1016/j.scitotenv.2021.148494
The ongoing COVID-19 pandemic has not only globally caused a high number of causalities, but is also an unprecedented challenge for scientists. False-positive virus detection tests not only aggravate the situation in the healthcare sector, but also provide ground for speculations. Previous studies have highlighted the importance of software choice and data interpretation in virome studies. We aimed to further expand theoretical and practical knowledge in bioinformatics-driven virome studies by focusing on short, virus-like DNA sequences in metagenomic data. Analyses of datasets obtained from different sample types (terrestrial, animal and human related samples) and origins showed that coronavirus-like sequences have existed in host-associated and environmental samples before the current COVID-19 pandemic. In the analyzed datasets, various Betacoronavirus-like sequences were detected that also included SARS-CoV-2 matches. Deepening analyses indicated that the detected sequences are not of viral origin and thus should not be considered in virome profiling approaches. Our study confirms the importance of parameter selection, especially in terms of read length, for reliable virome profiling. Natural environments are an important source of coronavirus-like nucleotide sequences that should be taken into account when virome datasets are analyzed and interpreted. We therefore suggest that processing parameters are carefully selected for SARS-CoV-2 profiling in host related as well as environmental samples in order to avoid incorrect identifications.
2021-06-24 2021 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2021.148494 Explorative assessment of coronavirus-like short sequences from host-associated and environmental metagenomes. Mora M, Wicaksono WA, Egamberdieva D, Krause R, Martinez JL, Cernava T, Berg G. Sci Total Environ. 2021; 793
Oral antiseptics against coronavirus: in-vitro and clinical evidence.
Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD.
J Hosp Infect. 2021; 113
DOI: 10.1016/j.jhin.2021.04.004
Angiotensin converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, so ACE2-expressing cells can act as target cells and are susceptible to infection. ACE2 receptors are highly expressed in the oral cavity, so this may be a potential high-risk route for SARS-CoV-2 infection. Furthermore, the virus can be detected in saliva, even before COVID-19 symptoms appear, with the consequent high risk of virus transmission in asymptomatic/presymptomatic patients. Reducing oral viral load could lead to a lower risk of transmission via salivary droplets or aerosols and therefore contribute to the control of the pandemic. Our aim was to evaluate the available evidence testing the in-vitro and in-vivo effects of oral antiseptics to inactivate or eradicate coronaviruses. The criteria used were those described in the PRISMA declaration for performing systematic reviews. An electronic search was conducted in Medline (via PubMed) and in Web of Sciences, using the MeSH terms: 'mouthwash' OR 'oral rinse' OR 'mouth rinse' OR 'povidone iodine' OR 'hydrogen peroxide' OR 'cetylpyridinium chloride' AND 'COVID-19' OR 'SARS-CoV-2' OR 'coronavirus' OR 'SARS' OR 'MERS'. The initial search strategy identified 619 articles on two electronic databases. Seventeen articles were included assessing the virucidal efficacy of oral antiseptics against coronaviruses. In conclusion, there is sufficient in-vitro evidence to support the use of antiseptics to potentially reduce the viral load of SARS-CoV-2 and other coronaviruses. However, in-vivo evidence for most oral antiseptics is limited. Randomized clinical trials with a control group are needed to demonstrate its clinical efficacy.
2021-04-15 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.jhin.2021.04.004 Oral antiseptics against coronavirus: in-vitro and clinical evidence. Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD. J Hosp Infect. 2021; 113
Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2.
Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, [...], Mira A.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-03461-y
Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742).
2021-12-22 2021 other research-article; Randomized Controlled Trial; Journal Article abstract-available 10.1038/s41598-021-03461-y Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, Puche-Torres M, Giner MJF, González AC, Coello JMS, Rueda IA, Aubá JMV, Español CC, Velasco AL, Abad DS, García-Esteban S, Artacho A, López-Labrador X, Mira A. Sci Rep. 2021; 11 (1)
Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents.
Godinho PIC, Soengas RG, Silva VLM.
Pharmaceuticals (Basel). 2021; 14 (6)
DOI: 10.3390/ph14060546
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world, creating a devastating socio-economic impact. Even though protective vaccines are starting to be administered, an effective antiviral agent for the prevention and treatment of COVID-19 is not available yet. Moreover, since new and deadly CoVs can emerge at any time with the potential of becoming pandemics, the development of therapeutic agents against potentially deadly CoVs is a research area of much current interest. In the search for anti-coronaviral drugs, researchers soon turned their heads towards glycosylated flavonoids. Glycosyl flavonoids, widespread in the plant kingdom, have received a lot of attention due to their widely recognized antioxidant, anti-inflammatory, neuroprotective, anticarcinogenic, antidiabetic, antimicrobial, and antiviral properties together with their capacity to modulate key cellular functions. The wide range of biological activities displayed by glycosyl flavonoids, along with their low toxicity, make them ideal candidates for drug development. In this review, we examine and discuss the up-to-date developments on glycosyl flavonoids as evidence-based natural sources of antivirals against coronaviruses and their potential role in the management of COVID-19.
2021-06-07 2021 other review-article; Review; Journal Article abstract-available 10.3390/ph14060546 Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents. Godinho PIC, Soengas RG, Silva VLM. Pharmaceuticals (Basel). 2021; 14 (6)
SARS-CoV-2 superinfection and reinfection with three different strains.
Pérez-Lago L, Kestler M, Sola-Campoy PJ, Rodriguez-Grande C, [...], Gregorio Marañón Microbiology-ID COVID 19 Study Group.
Transbound Emerg Dis. 2021;
DOI: 10.1111/tbed.14352
We report a corona virus disease (COVID-19) case with unprecedented viral complexity. In the first severe episode, two different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains (superinfection) were identified within a week. Three months after discharge, the patient was readmitted and was infected in a nosocomial outbreak with a different strain, suffering a second milder COVID-19 episode.
2021-10-23 2021 other brief-report; Journal Article abstract-available 10.1111/tbed.14352 SARS-CoV-2 superinfection and reinfection with three different strains. Pérez-Lago L, Kestler M, Sola-Campoy PJ, Rodriguez-Grande C, Flores-García RF, Buenestado-Serrano S, Herranz M, Alcalá L, Martínez-Laperche C, Suárez-González J, Catalán P, Muñoz P, García de Viedma D, Gregorio Marañón Microbiology-ID COVID 19 Study Group. Transbound Emerg Dis. 2021;
An Overview of Vaccines against SARS-CoV-2 in the COVID-19 Pandemic Era.
Pascual-Iglesias A, Canton J, Ortega-Prieto AM, Jimenez-Guardeño JM, [...], Regla-Nava JA.
Pathogens. 2021; 10 (8)
DOI: 10.3390/pathogens10081030
The emergence of SARS-CoV-2 in late 2019 led to the COVID-19 pandemic all over the world. When the virus was first isolated and its genome was sequenced in the early months of 2020, the efforts to develop a vaccine began. Based on prior well-known knowledge about coronavirus, the SARS-CoV-2 spike (S) protein was selected as the main target. Currently, more than one hundred vaccines are being investigated and several of them are already authorized by medical agencies. This review summarizes and compares the current knowledge about main approaches for vaccine development, focusing on those authorized and specifically their immunogenicity, efficacy preventing severe disease, adverse side effects, protection, and ability to cope with emergent SARS-CoV-2 variants.
2021-08-14 2021 other review-article; Review; Journal Article abstract-available 10.3390/pathogens10081030 An Overview of Vaccines against SARS-CoV-2 in the COVID-19 Pandemic Era. Pascual-Iglesias A, Canton J, Ortega-Prieto AM, Jimenez-Guardeño JM, Regla-Nava JA. Pathogens. 2021; 10 (8)
Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms
Toledano J, Moreno-Fernandez J, Puche-Juarez M, Ochoa J, [...], Diaz-Castro J.
Antioxidants (Basel). 2021; 11 (1)
DOI:
Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic.
2021-12-21 2021 other review-article; Review; Journal Article abstract-available Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms Toledano J, Moreno-Fernandez J, Puche-Juarez M, Ochoa J, Diaz-Castro J. Antioxidants (Basel). 2021; 11 (1)
[Reinfection by SARS-CoV-2: The first one in a family reported in Spain].
Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C.
Med Clin (Barc). 2021; 157 (9)
DOI: 10.1016/j.medcli.2021.04.009
2021-05-07 2021 other Letter 10.1016/j.medcli.2021.04.009 [Reinfection by SARS-CoV-2: The first one in a family reported in Spain]. Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C. Med Clin (Barc). 2021; 157 (9)
SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns.
Redondo N, Zaldívar-López S, Garrido JJ, Montoya M.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.708264
There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.
2021-07-07 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.708264 SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. Front Immunol. 2021; 12
Emergence of Bat-Related Betacoronaviruses: Hazard and Risks.
Frutos R, Serra-Cobo J, Pinault L, Lopez Roig M, [...], Devaux CA.
Front Microbiol. 2021; 12
DOI: 10.3389/fmicb.2021.591535
The current Coronavirus Disease 2019 (COVID-19) pandemic, with more than 111 million reported cases and 2,500,000 deaths worldwide (mortality rate currently estimated at 2.2%), is a stark reminder that coronaviruses (CoV)-induced diseases remain a major threat to humanity. COVID-19 is only the latest case of betacoronavirus (β-CoV) epidemics/pandemics. In the last 20 years, two deadly CoV epidemics, Severe Acute Respiratory Syndrome (SARS; fatality rate 9.6%) and Middle East Respiratory Syndrome (MERS; fatality rate 34.7%), plus the emergence of HCoV-HKU1 which causes the winter common cold (fatality rate 0.5%), were already a source of public health concern. Betacoronaviruses can also be a threat for livestock, as evidenced by the Swine Acute Diarrhea Syndrome (SADS) epizootic in pigs. These repeated outbreaks of β-CoV-induced diseases raise the question of the dynamic of propagation of this group of viruses in wildlife and human ecosystems. SARS-CoV, SARS-CoV-2, and HCoV-HKU1 emerged in Asia, strongly suggesting the existence of a regional hot spot for emergence. However, there might be other regional hot spots, as seen with MERS-CoV, which emerged in the Arabian Peninsula. β-CoVs responsible for human respiratory infections are closely related to bat-borne viruses. Bats are present worldwide and their level of infection with CoVs is very high on all continents. However, there is as yet no evidence of direct bat-to-human coronavirus infection. Transmission of β-CoV to humans is considered to occur accidentally through contact with susceptible intermediate animal species. This zoonotic emergence is a complex process involving not only bats, wildlife and natural ecosystems, but also many anthropogenic and societal aspects. Here, we try to understand why only few hot spots of β-CoV emergence have been identified despite worldwide bats and bat-borne β-CoV distribution. In this work, we analyze and compare the natural and anthropogenic environments associated with the emergence of β-CoV and outline conserved features likely to create favorable conditions for a new epidemic. We suggest monitoring South and East Africa as well as South America as these regions bring together many of the conditions that could make them future hot spots.
2021-03-15 2021 other review-article; Review; Journal Article abstract-available 10.3389/fmicb.2021.591535 Emergence of Bat-Related Betacoronaviruses: Hazard and Risks. Frutos R, Serra-Cobo J, Pinault L, Lopez Roig M, Devaux CA. Front Microbiol. 2021; 12
A Comparative Study between Spanish and British SARS-CoV-2 Variants.
Jimenez Ruiz JA, Lopez Ramirez C, Lopez-Campos JL.
Curr Issues Mol Biol. 2021; 43 (3)
DOI: 10.3390/cimb43030140
The study of the interaction between the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor is key to understanding binding affinity and stability. In the present report, we sought to investigate the differences between two already sequenced genome variants (Spanish and British) of SARS-CoV-2. Methods: In silico model evaluating the homology, identity and similarity in the genome sequence and the structure and alignment of the predictive spike by computational docking methods. Results: The identity results between the Spanish and British variants of the Spike protein were 28.67%. This close correspondence in the results between the Spanish and British SARS-CoV-2 variants shows that they are very similar (99.99%). The alignment obtained results in four deletions. There were 23 nucleotide substitutions also predicted which could affect the functionality of the proteins produced from this sequence. The interaction between the binding receptor domain from the spike protein and the ACE2 receptor produces some of the mutations found and, therefore, the energy of this ligand varies. However, the estimated antigenicity of the British variant is higher than its Spanish counterpart. Conclusions: Our results indicate that minimal mutations could interfere in the infectivity of the virus due to changes in the fitness between host cell recognition and interaction proteins. In particular, the N501Y substitution, situated in the RBD of the spike of the British variant, might be the reason for its extraordinary infective potential.
2021-11-16 2021 other Comparative Study; Journal Article abstract-available 10.3390/cimb43030140 A Comparative Study between Spanish and British SARS-CoV-2 Variants. Jimenez Ruiz JA, Lopez Ramirez C, Lopez-Campos JL. Curr Issues Mol Biol. 2021; 43 (3)
Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates.
Fakhri S, Nouri Z, Moradi SZ, Akkol EK, [...], Echeverría J.
Molecules. 2021; 26 (10)
DOI: 10.3390/molecules26102917
Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host-pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.
2021-05-14 2021 other review-article; Review; Journal Article abstract-available 10.3390/molecules26102917 Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates. Fakhri S, Nouri Z, Moradi SZ, Akkol EK, Piri S, Sobarzo-Sánchez E, Farzaei MH, Echeverría J. Molecules. 2021; 26 (10)
SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia.
Marín R, Pujol FH, Rojas D, Sobrevia L.
Biochim Biophys Acta Mol Basis Dis. 2022; 1868 (3)
DOI: 10.1016/j.bbadis.2021.166321
SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) also in pregnant women. Infection in pregnancy leads to maternal and placental functional alterations. Pregnant women with vascular defects such as preeclampsia show high susceptibility to SARS-CoV-2 infection by undefined mechanisms. Pregnant women infected with SARS-CoV-2 show higher rates of preterm birth and caesarean delivery, and their placentas show signs of vasculopathy and inflammation. It is still unclear whether the foetus is affected by the maternal infection with this virus and whether maternal infection associates with postnatal affections. The SARS-CoV-2 infection causes oxidative stress and activation of the immune system leading to cytokine storm and next tissue damage as seen in the lung. The angiotensin-converting-enzyme 2 expression is determinant for these alterations in the lung. Since this enzyme is expressed in the human placenta, SARS-CoV-2 could infect the placenta tissue, although reported to be of low frequency compared with maternal lung tissue. Early-onset preeclampsia (eoPE) shows higher expression of ADAM17 (a disintegrin and metalloproteinase 17) causing an imbalanced renin-angiotensin system and endothelial dysfunction. A similar mechanism seems to potentially account for SARS-CoV-2 infection. This review highlights the potentially common characteristics of pregnant women with eoPE with those with COVID-19. A better understanding of the mechanisms of SARS-CoV-2 infection and its impact on the placenta function is determinant since eoPE/COVID-19 association may result in maternal metabolic alterations that might lead to a potential worsening of the foetal programming of diseases in the neonate, young, and adult.
2021-12-14 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.bbadis.2021.166321 SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia. Marín R, Pujol FH, Rojas D, Sobrevia L. Biochim Biophys Acta Mol Basis Dis. 2022; 1868 (3)
Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).
Cenko E, Badimon L, Bugiardini R, Claeys MJ, [...], Tousoulis D.
Cardiovasc Res. 2021; 117 (14)
DOI: 10.1093/cvr/cvab298
The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.
2021-12-01 2021 other Consensus Development Conference; review-article; Journal Article abstract-available 10.1093/cvr/cvab298 Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA). Cenko E, Badimon L, Bugiardini R, Claeys MJ, De Luca G, de Wit C, Derumeaux G, Dorobantu M, Duncker DJ, Eringa EC, Gorog DA, Hassager C, Heinzel FR, Huber K, Manfrini O, Milicic D, Oikonomou E, Padro T, Trifunovic-Zamaklar D, Vasiljevic-Pokrajcic Z, Vavlukis M, Vilahur G, Tousoulis D. Cardiovasc Res. 2021; 117 (14)
Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity.
Saiz ML, De Diego ML, López-García D, Corte-Iglesias V, [...], Suarez-Alvarez B.
Clin Epigenetics. 2021; 13 (1)
DOI: 10.1186/s13148-021-01168-5

Background

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors for entry into cells, and the serine protease TMPRSS2 for S protein priming. Inhibition of protease activity or the engagement with ACE2 and NRP1 receptors has been shown to be an effective strategy for blocking infectivity and viral spreading. Valproic acid (VPA; 2-propylpentanoic acid) is an epigenetic drug approved for clinical use. It produces potent antiviral and anti-inflammatory effects through its function as a histone deacetylase (HDAC) inhibitor. Here, we propose VPA as a potential candidate to tackle COVID-19, in which rapid viral spread and replication, and hyperinflammation are crucial elements.

Results

We used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, and BEAS-2B) to analyze the effect of VPA and other HDAC inhibitors on the expression of the ACE-2 and NRP-1 receptors and their ability to inhibit infectivity, viral production, and the inflammatory response. Treatment with VPA significantly reduced expression of the ACE2 and NRP1 host proteins in all cell lines through a mechanism mediated by its HDAC inhibitory activity. The effect is maintained after SARS-CoV-2 infection. Consequently, the treatment of cells with VPA before infection impairs production of SARS-CoV-2 infectious viruses, but not that of other ACE2- and NRP1-independent viruses (VSV and HCoV-229E). Moreover, the addition of VPA 1 h post-infection with SARS-CoV-2 reduces the production of infectious viruses in a dose-dependent manner without significantly modifying the genomic and subgenomic messenger RNAs (gRNA and sg mRNAs) or protein levels of N protein. The production of inflammatory cytokines (TNF-α and IL-6) induced by TNF-α and SARS-CoV-2 infection is diminished in the presence of VPA.

Conclusions

Our data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.
2021-10-11 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s13148-021-01168-5 Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity. Saiz ML, De Diego ML, López-García D, Corte-Iglesias V, Baragaño Raneros A, Astola I, Asensi V, López-Larrea C, Suarez-Alvarez B. Clin Epigenetics. 2021; 13 (1)
High SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity.
Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, [...], Martínez I.
J Infect Dis. 2021;
DOI: 10.1093/infdis/jiab604
Mucosal immune response in the upper respiratory tract is crucial for the initial control of viral replication, the clearance of SARS-CoV-2, and the progression of the coronavirus disease 2019 (COVID-19). We analyzed the SARS-CoV-2 RNA load and the expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2 infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in the nasopharyngeal mucosa induces the expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with ICU admission or death, although CCL5 was the best predictor of COVID-19 severity.
2021-12-15 2021 fondo-covid brief-report; Journal Article abstract-available 10.1093/infdis/jiab604 High SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity. Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, Muñoz-Gomez MJ, Hervás Fernández I, González Ventosa V, Vidal-Alcántara EJ, Cuadros-González J, Bermejo-Martin JF, Resino S, Martínez I. J Infect Dis. 2021;
Relevance of BET Family Proteins in SARS-CoV-2 Infection.
Lara-Ureña N, García-Domínguez M.
Biomolecules. 2021; 11 (8)
DOI: 10.3390/biom11081126
The recent pandemic we are experiencing caused by the coronavirus disease 2019 (COVID-19) has put the world's population on the rack, with more than 191 million cases and more than 4.1 million deaths confirmed to date. This disease is caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A massive proteomic analysis has revealed that one of the structural proteins of the virus, the E protein, interacts with BRD2 and BRD4 proteins of the Bromodomain and Extra Terminal domain (BET) family of proteins. BETs are essential to cell cycle progression, inflammation and immune response and have also been strongly associated with infection by different types of viruses. The fundamental role BET proteins play in transcription makes them appropriate targets for the propagation strategies of some viruses. Recognition of histone acetylation by BET bromodomains is essential for transcription control. The development of drugs mimicking acetyl groups, and thereby able to displace BET proteins from chromatin, has boosted interest on BETs as attractive targets for therapeutic intervention. The success of these drugs against a variety of diseases in cellular and animal models has been recently enlarged with promising results from SARS-CoV-2 infection studies.
2021-07-30 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/biom11081126 Relevance of BET Family Proteins in SARS-CoV-2 Infection. Lara-Ureña N, García-Domínguez M. Biomolecules. 2021; 11 (8)
Effective presence of antibodies against common human coronavirus in IgG immunoglobulin medicinal products.: Antibodies to common coronaviruses in IgG medicinal products.
Díez JM, Romero C, Gajardo R.
Int J Infect Dis. 2021;
DOI: 10.1016/j.ijid.2021.12.329

Background

In these studies, immunoglobulin (IgG) products (IV, IM, SC) prepared from geographically diverse plasma pools were tested for activity against common human coronaviruses (HCoV). Products from plasma obtained from Germany, Czech Republic, Slovak Republic, USA, and Spain were tested for antibodies to common HCoV: 229E, OC43, NL63, and HKU1. Since these products are manufactured from pooled plasma from thousands of donors, the antibodies therein are representative of HCoV exposure in the population at large.

Methods

IgG products were tested for antibodies to four common HCoV by ELISA. Neutralization assays were conducted using HCoV-229E cultured onto MRC5 cells.

Results

The ELISA assays showed that when expressed as specific activity (anti-HCoV activity/mg IgG) similar activity against the four common HCoV was seen across the IgG products regardless of concentration or geographic origin. Highest anti-HCoV activity was seen against HCoV-229E, followed by HCoV-OC43, and then HCoV-NL63 and HCoV-HKU1. The neutralization assays showed similar potency for two preparations of IgG prepared by different processes.

Conclusions

This is the first demonstration of antibodies to common HCoV in IgG products. These results may explain the cross-reactivity seen with pre-pandemic IgG products and SARS-CoV-2 and contribute to the variability in disease course in different patients.
2021-12-17 2021 other research-article; Journal Article abstract-available 10.1016/j.ijid.2021.12.329 Effective presence of antibodies against common human coronavirus in IgG immunoglobulin medicinal products.: Antibodies to common coronaviruses in IgG medicinal products. Díez JM, Romero C, Gajardo R. Int J Infect Dis. 2021;
The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients.
Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, [...], Ruiz R.
Front Aging Neurosci. 2021; 13
DOI: 10.3389/fnagi.2021.632673
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. Also, some cases progress to acute respiratory distress syndrome (ARDS). The acute phase of COVID-19 has been also related to nervous system symptoms, including loss of taste and smell as well as encephalitis and cerebrovascular disorders. However, it remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they appear as a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response. Importantly, the medium and long-term consequences of the infection by SARS-CoV-2 in the nervous system remain at present unknown. This review article aims to give an overview of the current neurological symptoms associated with COVID-19, as well as attempting to provide an insight beyond the acute affectation.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3389/fnagi.2021.632673 The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients. Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, Martínez E, Ruiz-Mateos E, Deierborg T, Venero JL, Real LM, Ruiz R. Front Aging Neurosci. 2021; 13
The Positive Rhinovirus/Enterovirus Detection and SARS-CoV-2 Persistence beyond the Acute Infection Phase: An Intra-Household Surveillance Study.
Brotons P, Jordan I, Bassat Q, Henares D, [...], Muñoz-Almagro C.
Viruses. 2021; 13 (8)
DOI: 10.3390/v13081598
We aimed to assess the duration of nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA persistence in adults self-confined at home after acute infection; and to identify the associations of SARS-CoV-2 persistence with respiratory virus co-detection and infection transmission. A cross-sectional intra-household study was conducted in metropolitan Barcelona (Spain) during the time period of April to June 2020. Every adult who was the first family member reported as SARS-CoV-2-positive by reverse transcription polymerase chain reaction (RT-PCR) as well as their household child contacts had nasopharyngeal swabs tested by a targeted SARS-CoV-2 RT-PCR and a multiplex viral respiratory panel after a 15 day minimum time lag. Four-hundred and four households (404 adults and 708 children) were enrolled. SARS-CoV-2 RNA was detected in 137 (33.9%) adults and 84 (11.9%) children. Rhinovirus/Enterovirus (RV/EV) was commonly found (83.3%) in co-infection with SARS-CoV-2 in adults. The mean duration of SARS-CoV-2 RNA presence in adults' nasopharynx was 52 days (range 26-83 days). The persistence of SARS-CoV-2 was significantly associated with RV/EV co-infection (adjusted odds ratio (aOR) 9.31; 95% CI 2.57-33.80) and SARS-CoV-2 detection in child contacts (aOR 2.08; 95% CI 1.24-3.51). Prolonged nasopharyngeal SARS-CoV-2 RNA persistence beyond the acute infection phase was frequent in adults quarantined at home during the first epidemic wave; which was associated with RV/EV co-infection and could enhance intra-household infection transmission.
2021-08-12 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13081598 The Positive Rhinovirus/Enterovirus Detection and SARS-CoV-2 Persistence beyond the Acute Infection Phase: An Intra-Household Surveillance Study. Brotons P, Jordan I, Bassat Q, Henares D, Fernandez de Sevilla M, Ajanovic S, Redin A, Fumado V, Baro B, Claverol J, Varo R, Cuadras D, Hecht J, Barrabeig I, Garcia-Garcia JJ, Launes C, Muñoz-Almagro C. Viruses. 2021; 13 (8)
Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?
Soldevila B, Puig-Domingo M, Marazuela M.
Rev Endocr Metab Disord. 2021;
DOI: 10.1007/s11154-021-09678-6
Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.
2021-07-31 2021 other review-article; Review; Journal Article abstract-available 10.1007/s11154-021-09678-6 Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated? Soldevila B, Puig-Domingo M, Marazuela M. Rev Endocr Metab Disord. 2021;
COVID-19 pneumonia: A review of typical radiological characteristics.
Churruca M, Martínez-Besteiro E, Couñago F, Landete P.
World J Radiol. 2021; 13 (10)
DOI: 10.4329/wjr.v13.i10.327
Coronavirus disease 2019 (COVID-19) was first discovered after unusual cases of severe pneumonia emerged by the end of 2019 in Wuhan (China) and was declared a global public health emergency by the World Health Organization in January 2020. The new pathogen responsible for the infection, genetically similar to the beta-coronavirus family, is known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the current gold standard diagnostic tool for its detection in respiratory samples is the reverse transcription-polymerase chain reaction test. Imaging findings on COVID-19 have been widely described in studies published throughout last year, 2020. In general, ground-glass opacities and consolidations, with a bilateral and peripheral distribution, are the most typical patterns found in COVID-19 pneumonia. Even though much of the literature focuses on chest computed tomography (CT) and X-ray imaging and their findings, other imaging modalities have also been useful in the assessment of COVID-19 patients. Lung ultrasonography is an emerging technique with a high sensitivity, and thus useful in the initial evaluation of SARS-CoV-2 infection. In addition, combined positron emission tomography-CT enables the identification of affected areas and follow-up treatment responses. This review intends to clarify the role of the imaging modalities available and identify the most common radiological manifestations of COVID-19.
2021-10-01 2021 other review-article; Review; Journal Article abstract-available 10.4329/wjr.v13.i10.327 COVID-19 pneumonia: A review of typical radiological characteristics. Churruca M, Martínez-Besteiro E, Couñago F, Landete P. World J Radiol. 2021; 13 (10)
Neuropilin-1: A feasible link between liver pathologies and COVID-19.
Benedicto A, García-Kamiruaga I, Arteta B.
World J Gastroenterol. 2021; 27 (24)
DOI: 10.3748/wjg.v27.i24.3516
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a tremendous impact on the health of millions of people worldwide. Unfortunately, those suffering from previous pathological conditions are more vulnerable and tend to develop more severe disease upon infection with the new SARS-CoV-2. This coronavirus interacts with the angiotensin-converting enzyme 2 receptor to invade the cells. Recently, another receptor, neuropilin-1 (NRP-1), has been reported to amplify the viral infection. Interestingly, NRP-1 is expressed in nonparenchymal liver cells and is related to and upregulated in a wide variety of liver-related pathologies. It has been observed that SARS-CoV-2 infection promotes liver injury through several pathways that may be influenced by the previous pathological status of the patient and liver expression of NRP-1. Moreover, coronavirus disease 2019 causes an inflammatory cascade called cytokine storm in patients with severe disease. This cytokine storm may influence liver sinusoidal-cell phenotype, facilitating viral invasion. In this review, the shreds of evidence linking NRP-1 with liver pathologies such as hepatocellular carcinoma, liver fibrosis, nonalcoholic fatty liver disease and inflammatory disorders are discussed in the context of SARS-CoV-2 infection. In addition, the involvement of the infection-related cytokine storm in NRP-1 overexpression and the subsequent increased risk of SARS-CoV-2 infection are also analyzed. This review aims to shed some light on the involvement of liver NRP-1 during SARS-CoV-2 infection and emphasizes the possible involvement this receptor with the observed liver damage.
2021-06-01 2021 other review-article; Review; Journal Article abstract-available 10.3748/wjg.v27.i24.3516 Neuropilin-1: A feasible link between liver pathologies and COVID-19. Benedicto A, García-Kamiruaga I, Arteta B. World J Gastroenterol. 2021; 27 (24)
Confirmation of SARS-CoV-2 airborne dissemination indoors using "COVID-19 traps".
Orenes-Piñero E, Navas-Carrillo D, Moreno-Docón A, Ortega-García JA, [...], Ramírez P.
J Infect. 2021;
DOI: 10.1016/j.jinf.2021.12.017
2021-12-22 2021 other research-article; Journal Article 10.1016/j.jinf.2021.12.017 Confirmation of SARS-CoV-2 airborne dissemination indoors using "COVID-19 traps". Orenes-Piñero E, Navas-Carrillo D, Moreno-Docón A, Ortega-García JA, Torres-Cantero AM, García-Vázquez E, Ramírez P. J Infect. 2021;
SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells.
Barreda D, Santiago C, Rodríguez JR, Rodríguez JF, [...], Ávila-Flores A.
Cells. 2021; 10 (12)
DOI: 10.3390/cells10123279
Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols. Here we evaluated human DCs in response to SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain (RBD) challenge. Both proteins increased the expression of maturation markers, including MHC molecules and costimulatory receptors. DCs interaction with the SARS-CoV-2 S protein promotes activation of key signaling molecules involved in inflammation, including MAPK, AKT, STAT1, and NFκB, which correlates with the expression and secretion of distinctive proinflammatory cytokines. Differences in the expression of ACE2 along the differentiation of human monocytes to mature DCs and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes inflammatory response and provides molecular links between individual variations and the degree of response against this virus.
2021-11-23 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/cells10123279 SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells. Barreda D, Santiago C, Rodríguez JR, Rodríguez JF, Casasnovas JM, Mérida I, Ávila-Flores A. Cells. 2021; 10 (12)
The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19.
García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, [...], Moreno R.
Heart Fail Rev. 2021; 26 (4)
DOI: 10.1007/s10741-020-10066-6
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1-7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.
2021-01-06 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10741-020-10066-6 The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19. García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, García-Rodríguez J, Moreno R. Heart Fail Rev. 2021; 26 (4)
Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update.
Anand U, Jakhmola S, Indari O, Jha HC, [...], Pérez de la Lastra JM.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.658519
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.
2021-06-30 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.658519 Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update. Anand U, Jakhmola S, Indari O, Jha HC, Chen ZS, Tripathi V, Pérez de la Lastra JM. Front Immunol. 2021; 12
In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2.
Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, [...], Ruocco G.
Front Mol Biosci. 2021; 8
DOI: 10.3389/fmolb.2021.690655
We propose a computational investigation on the interaction mechanisms between SARS-CoV-2 spike protein and possible human cell receptors. In particular, we make use of our newly developed numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular isoelectronic density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, which was unfeasible with previous methods. Our results indicate that SARS-CoV-2 uses a dual strategy: in addition to the known interaction with angiotensin-converting enzyme 2, the viral spike protein can also interact with sialic-acid receptors of the cells in the upper airways.
2021-06-09 2021 other research-article; Journal Article abstract-available 10.3389/fmolb.2021.690655 In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2. Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, Monti M, Golbek TW, Gosti G, Roeters SJ, Weidner T, Otzen DE, Ruocco G. Front Mol Biosci. 2021; 8
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease.
Sugiyama MG, Cui H, Redka DS, Karimzadeh M, [...], Antonescu CN.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-02432-7
The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
2021-12-02 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-02432-7 Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease. Sugiyama MG, Cui H, Redka DS, Karimzadeh M, Rujas E, Maan H, Hayat S, Cheung K, Misra R, McPhee JB, Viirre RD, Haller A, Botelho RJ, Karshafian R, Sabatinos SA, Fairn GD, Madani Tonekaboni SA, Windemuth A, Julien JP, Shahani V, MacKinnon SS, Wang B, Antonescu CN. Sci Rep. 2021; 11 (1)
Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies.
Martí D, Alsina M, Alemán C, Bertran O, [...], Torras J.
Biochimie. 2021;
DOI: 10.1016/j.biochi.2021.10.013
Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 μs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.
2021-10-25 2021 other research-article; Journal Article abstract-available 10.1016/j.biochi.2021.10.013 Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies. Martí D, Alsina M, Alemán C, Bertran O, Turon P, Torras J. Biochimie. 2021;
Physical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy?
Fernández-Lázaro D, González-Bernal JJ, Sánchez-Serrano N, Navascués LJ, [...], Mielgo-Ayuso J.
Int J Environ Res Public Health. 2020; 17 (22)
DOI: 10.3390/ijerph17228496
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) is a novel coronavirus not previously recognized in humans until late 2019. On 31 December 2019, a cluster of cases of pneumonia of unspecified etiology was reported to the World Health Organization in China. The availability of adequate SARS-CoV-2 drugs is also limited, and the efficacy and safety of these drugs for COVID-2019 pneumonia patients need to be assessed by further clinical trials. For these reasons, there is a need for other strategies against COVID-19 that are capable of prevention and treatment. Physical exercise has proven to be an effective therapy for most chronic diseases and microbial infections with preventive/therapeutic benefits, considering that exercise involves primary immunological mediators and/or anti-inflammatory properties. This review aimed to provide an insight into how the implementation of a physical exercise program against COVID-19 may be a useful complementary tool for prevention, which can also enhance recovery, improve quality of life, and provide immune protection against SARS-CoV-2 virus infection in the long term. In summary, physical exercise training exerts immunomodulatory effects, controls the viral gateway, modulates inflammation, stimulates nitric oxide synthesis pathways, and establishes control over oxidative stress.
2020-11-17 2020 other review-article; Review; Journal Article abstract-available 10.3390/ijerph17228496 Physical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy? Fernández-Lázaro D, González-Bernal JJ, Sánchez-Serrano N, Navascués LJ, Ascaso-Del-Río A, Mielgo-Ayuso J. Int J Environ Res Public Health. 2020; 17 (22)
SARS-CoV-2: what it is, how it acts, and how it manifests in imaging studies☆ SARS-CoV-2: cómo es, cómo actúa y cómo se expresa en la imagen
Fernández-Pérez G, Oñate Miranda M, Fernández-Rodríguez P, Velasco Casares M, [...], Oñate Cuchat J.
Radiologia (Engl Ed). 2021; 63 (2)
DOI:
COVID-19 is a disease with many clinical, biochemical, and radiological signs that has a predilection for the lungs, probably because of the high number of ACE-2 receptors in this organ. The infection of cells activates proinflammatory substances, causing diffuse alveolar damage, which is the histopathological basis of ARDS. The exudative phase would manifest as ground-glass opacities and consolidation, and the proliferative phase would manifest as a tendency toward a more linear morphology. Both CT and PET/CT findings support the inflammatory character of the lung lesions in the initial phase of the disease and in patients with mild-moderate disease. Severe cases have pulmonary hypoperfusion that is likely due to abnormal alveolar ventilation and perfusion. On the other hand, a prothrombotic state increases the risk of thromboembolic disease through the activation of coagulation and platelet pathways with the production of fibrin degradation products (D-dimer) and consumption of platelets.
2021-01-01 2021 other research-article; Journal Article abstract-available SARS-CoV-2: what it is, how it acts, and how it manifests in imaging studies☆ SARS-CoV-2: cómo es, cómo actúa y cómo se expresa en la imagen Fernández-Pérez G, Oñate Miranda M, Fernández-Rodríguez P, Velasco Casares M, Corral de la Calle M, Franco López Á, Díez Blanco M, Oñate Cuchat J. Radiologia (Engl Ed). 2021; 63 (2)
Decoding molnupiravir-induced mutagenesis in SARS-CoV-2.
Menéndez-Arias L.
J Biol Chem. 2021; 297 (1)
DOI: 10.1016/j.jbc.2021.100867
Molnupiravir, a prodrug of the nucleoside derivative β-D-N4-hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA and subsequently extended and used as template for RNA-dependent RNA synthesis, proposing a mutagenesis model consistent with available virological evidence. Their study uncovers molecular mechanisms by which molnupiravir drives SARS-CoV-2 into error catastrophe.
2021-06-09 2021 other Research Support, Non-U.S. Gov't; discussion; Journal Article abstract-available 10.1016/j.jbc.2021.100867 Decoding molnupiravir-induced mutagenesis in SARS-CoV-2. Menéndez-Arias L. J Biol Chem. 2021; 297 (1)
The Development of SARS-CoV-2 Variants: The Gene Makes the Disease.
Perez-Gomez R.
J Dev Biol. 2021; 9 (4)
DOI: 10.3390/jdb9040058
A novel coronavirus (SARS-CoV-2) emerged towards the end of 2019 that caused a severe respiratory disease in humans called COVID-19. It led to a pandemic with a high rate of morbidity and mortality that is ongoing and threatening humankind. Most of the mutations occurring in SARS-CoV-2 are synonymous or deleterious, but a few of them produce improved viral functions. The first known mutation associated with higher transmissibility, D614G, was detected in early 2020. Since then, the virus has evolved; new mutations have occurred, and many variants have been described. Depending on the genes affected and the location of the mutations, they could provide altered infectivity, transmissibility, or immune escape. To date, mutations that cause variations in the SARS-CoV-2 spike protein have been among the most studied because of the protein's role in the initial virus-cell contact and because it is the most variable region in the virus genome. Some concerning mutations associated with an impact on viral fitness have been described in the Spike protein, such as D614G, N501Y, E484K, K417N/T, L452R, and P681R, among others. To understand the impact of the infectivity and antigenicity of the virus, the mutation landscape of SARS-CoV-2 has been under constant global scrutiny. The virus variants are defined according to their origin, their genetic profile (some characteristic mutations prevalent in the lineage), and the severity of the disease they produce, which determines the level of concern. If they increase fitness, new variants can outcompete others in the population. The Alpha variant was more transmissible than previous versions and quickly spread globally. The Beta and Gamma variants accumulated mutations that partially escape the immune defenses and affect the effectiveness of vaccines. Nowadays, the Delta variant, identified around March 2021, has spread and displaced the other variants, becoming the most concerning of all lineages that have emerged. The Delta variant has a particular genetic profile, bearing unique mutations, such as T478K in the spike protein and M203R in the nucleocapsid. This review summarizes the current knowledge of the different mutations that have appeared in SARS-CoV-2, mainly on the spike protein. It analyzes their impact on the protein function and, subsequently, on the level of concern of different variants and their importance in the ongoing pandemic.
2021-12-15 2021 other review-article; Review; Journal Article abstract-available 10.3390/jdb9040058 The Development of SARS-CoV-2 Variants: The Gene Makes the Disease. Perez-Gomez R. J Dev Biol. 2021; 9 (4)
Personal and vaccination history as factors associated with SARS-CoV-2 infection.
Fernández-Prada M, García-González P, García-Morán A, Ruiz-Álvarez I, [...], Calvo-Rodríguez C.
Med Clin (Engl Ed). 2021; 157 (5)
DOI: 10.1016/j.medcle.2021.02.007

Background and objective

SARS-CoV-2 has been and is a major global Public Health challenge. Since the beginning of the pandemic, different comorbidities have been postulated and associated with spectra of increased severity and mortality. The objectives of this research are: 1) to analyse the factors associated with SARS-CoV-2 infection (COVID-19) in a health area in northern Spain; 2) to understand the possible role of influenza vaccination and pneumococcal vaccination in the development of COVID-19.

Materials and method

A test-negative case-control study was conducted. Variables related to personal and vaccination history were considered. Although the epidemiological definition of the case varied over time, the reference definition was that corresponding to 31/01/2020 in Spain. A bivariate and multivariate analysis was performed.

Results

The sample included 188 patients, of which 63 were cases and 125 controls. The results show that obesity increases the risk 2.4-fold of suffering this infection (IC 95% 1,301-4,521) and ARA-2 increases it 2.2-fold (95% CI 1,256-6,982). On the other hand, anti-pneumococcal vaccination of 13 serotypes showed results close to statistical significance (OR = 0.4; 95% CI 0.170-1,006).

Conclusion

Obesity and the use of ARA-2 increases the risk of COVID-19. Scientific knowledge about factors associated with COVID-19 should be expanded. The authors consider that the present research raises the need further investigate the role of vaccines in this infection and their possible heterologous properties.
2021-08-09 2021 other research-article; Journal Article abstract-available 10.1016/j.medcle.2021.02.007 Personal and vaccination history as factors associated with SARS-CoV-2 infection. Fernández-Prada M, García-González P, García-Morán A, Ruiz-Álvarez I, Ramas-Diez C, Calvo-Rodríguez C. Med Clin (Engl Ed). 2021; 157 (5)
Surviving Older Patients Show Preserved Cellular and Humoral Immunological Memory Several Months After SARS-CoV-2 Infection.
García-Torre A, Bueno-García E, López-Martínez R, Rioseras B, [...], Alonso-Arias R.
J Gerontol A Biol Sci Med Sci. 2022; 77 (1)
DOI: 10.1093/gerona/glab206
Understanding how older people respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical if we are to confront the coronavirus disease 2019 (COVID-19) pandemic and establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analyzed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by interferon-γ (IFN-γ) and granzyme B release by ELISpot; memory B-lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than 7 months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG.
2022-01-01 2022 fondo-covid Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/gerona/glab206 Surviving Older Patients Show Preserved Cellular and Humoral Immunological Memory Several Months After SARS-CoV-2 Infection. García-Torre A, Bueno-García E, López-Martínez R, Rioseras B, Moro-García MA, Alonso-Alvarez S, Lluna-González A, Sousa-Fernández A, Fernández-Gudin M, Campos-Riopedre L, Castro-Del Cueto C, Pérez-Fernández AB, Alonso-Rodríguez A, Menéndez-Peña C, Menéndez-Peña L, García-Arnaldo N, Feito-Díaz E, Fernández-Lorences A, Fraile-Manzano A, Fernández-Iglesias C, Rivera JA, Pérez-Fonseca C, Urdiales-Ruano E, Debán-Fernández M, Mendes-Moreira H, Herrero-Puente P, Alonso-Arias R. J Gerontol A Biol Sci Med Sci. 2022; 77 (1)
Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease.
Todorović-Raković N, Whitfield JR.
Cytokine. 2021; 146
DOI: 10.1016/j.cyto.2021.155637
Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections. Here we consider the controversial roles of effectors like IFNγ, discussing its actions in immunomodulation and immunotolerance. We explore the possibility that modulation of IFNγ could be used to influence the course of such infections. Importantly, not only could endogenous expression of IFNγ influence the outcome, there are existing IFNγ therapeutics that can readily be applied in the clinic. However, our understanding of the molecular mechanisms controlled by IFNγ suggests that the exact timing for application of IFNγ-based therapeutics could be crucial: it should be earlier to significantly reduce the viral load and thus decrease the overall severity of the disease.
2021-07-03 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.cyto.2021.155637 Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease. Todorović-Raković N, Whitfield JR. Cytokine. 2021; 146
Immunological and physiopathological approach of COVID-19 in pregnancy.
Ferrer-Oliveras R, Mendoza M, Capote S, Pratcorona L, [...], Alijotas-Reig J.
Arch Gynecol Obstet. 2021; 304 (1)
DOI: 10.1007/s00404-021-06061-3
Coronavirus disease-2019 (COVID-19) related to Coronavirus-2 (SARS-CoV-2) is a worldwide health concern. Despite the majority of patients will evolve asymptomatic or mild-moderate upper respiratory tract infections, 20% will develop severe disease. Based on current pathogenetic knowledge, a severe COVID-19 form is mainly a hyperinflammatory, immune-mediated disorder, triggered by a viral infection. Due to their particular immunological features, pregnant women are supposed to be particularly susceptible to complicate by intracellular infections as well as immunological disturbances. As an example, immune-thrombosis has been identified as a common immune-mediated and pathogenic phenomenon both in COVID-19, in obstetric diseases and in COVID-19 pregnant women. According to extensive published clinical data, is rationale to expect an interference with the normal development of pregnancy in selected SARS-CoV-2-infected cases, mainly during third trimester.This manuscript provides insights of research to elucidate the potential harmful responses to SARS-CoV-2 and /or other coronavirus infections, as well as bidirectional interactions between COVID-19 and pregnancy to improve their respective management.
2021-05-04 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1007/s00404-021-06061-3 Immunological and physiopathological approach of COVID-19 in pregnancy. Ferrer-Oliveras R, Mendoza M, Capote S, Pratcorona L, Esteve-Valverde E, Cabero-Roura L, Alijotas-Reig J. Arch Gynecol Obstet. 2021; 304 (1)
Rhabdomyolysis as the main manifestation of coronavirus disease 2019.
Rivas-García S, Bernal J, Bachiller-Corral J.
Rheumatology (Oxford). 2020; 59 (8)
DOI: 10.1093/rheumatology/keaa351
2020-08-01 2020 other Letter; Comment 10.1093/rheumatology/keaa351 Rhabdomyolysis as the main manifestation of coronavirus disease 2019. Rivas-García S, Bernal J, Bachiller-Corral J. Rheumatology (Oxford). 2020; 59 (8)
Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment
Blanch-Ruiz M, Ortega-Luna R, Gómez-García G, Martínez-Cuesta M, [...], Álvarez Á.
Biomedicines. 2021; 10 (1)
DOI:
The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.
2021-12-23 2021 other review-article; Review; Journal Article abstract-available Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment Blanch-Ruiz M, Ortega-Luna R, Gómez-García G, Martínez-Cuesta M, Álvarez Á. Biomedicines. 2021; 10 (1)
SARS-CoV-2 research using human pluripotent stem cells and organoids.
Deguchi S, Serrano-Aroca Á, Tambuwala MM, Uhal BD, [...], Takayama K.
Stem Cells Transl Med. 2021; 10 (11)
DOI: 10.1002/sctm.21-0183
Experimental cell models are indispensable for clarifying the pathophysiology of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and for developing therapeutic agents. To recapitulate the symptoms and drug response of COVID-19 patients in vitro, SARS-CoV-2 studies using physiologically relevant human embryonic stem (ES)/induced pluripotent stem (iPS) cell-derived somatic cells and organoids are ongoing. These cells and organoids have been used to show that SARS-CoV-2 can infect and damage various organs including the lung, heart, brain, intestinal tract, kidney, and pancreas. They are also being used to develop COVID-19 therapeutic agents, including evaluation of their antiviral efficacy and safety. The relationship between COVID-19 aggravation and human genetic backgrounds has been investigated using genetically modified ES/iPS cells and patient-derived iPS cells. This review summarizes the latest results and issues of SARS-CoV-2 research using human ES/iPS cell-derived somatic cells and organoids.
2021-07-24 2021 other research-article; Review; Journal Article abstract-available 10.1002/sctm.21-0183 SARS-CoV-2 research using human pluripotent stem cells and organoids. Deguchi S, Serrano-Aroca Á, Tambuwala MM, Uhal BD, Brufsky AM, Takayama K. Stem Cells Transl Med. 2021; 10 (11)
Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses.
Fernández-Bellon H, Rodon J, Fernández-Bastit L, Almagro V, [...], Vergara-Alert J.
Viruses. 2021; 13 (9)
DOI: 10.3390/v13091683
To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.
2021-08-25 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13091683 Monitoring Natural SARS-CoV-2 Infection in Lions (<i>Panthera leo</i>) at the Barcelona Zoo: Viral Dynamics and Host Responses. Fernández-Bellon H, Rodon J, Fernández-Bastit L, Almagro V, Padilla-Solé P, Lorca-Oró C, Valle R, Roca N, Grazioli S, Trogu T, Bensaid A, Carrillo J, Izquierdo-Useros N, Blanco J, Parera M, Noguera-Julián M, Clotet B, Moreno A, Segalés J, Vergara-Alert J. Viruses. 2021; 13 (9)
Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19).
Bassat Q, Varo R, Hurtado JC, Marimon L, [...], Rakislova N.
Clin Infect Dis. 2021; 73 (Suppl_5)
DOI: 10.1093/cid/ciab760

Background

Infectious diseases' outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room.

Methods

We aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths.

Results

After a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19-related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related damage could be evaluated.

Conclusions

MITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected-and under which exact biosafety measures-are necessary to facilitate and expand its use globally.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/cid/ciab760 Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19). Bassat Q, Varo R, Hurtado JC, Marimon L, Ferrando M, Ismail MR, Carrilho C, Fernandes F, Castro P, Maixenchs M, Rodrigo-Calvo MT, Guerrero J, Martínez A, Lacerda MVG, Mandomando I, Menéndez C, Martinez MJ, Ordi J, Rakislova N. Clin Infect Dis. 2021; 73 (Suppl_5)
Virucidal Activity of Different Mouthwashes Using a Novel Biochemical Assay
Rodríguez-Casanovas H, la Rosa M, Bello-Lemus Y, Rasperini G, [...], Acosta-Hoyos A.
Healthcare (Basel). 2021; 10 (1)
DOI:
Background: Saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is not insignificant, and procedures for reducing viral loads in the oral cavity have been proposed. Little research to date has been performed on the effect of mouthwashes on the SARS-CoV-2 virus, and some of their mechanisms of action remain unknown. Methods: SARS-CoV-2 positive nasopharyngeal swabs measured by RT-PCR were used for virucidal activity in a 1:1 ratio, with an incubation time of 1 min. The solutions used in this study were: iodopovidone (8 mg); * D-limonene, a terpene extracted from citrus peels (0.3%); † cetylpyridinium chloride (0.1%) (CPC); ‡ chlorhexidine gluconate (10%) (CHX); § a CPC (0.12%) and CHX (0.05%) containing formula; ** a formula containing essential oils; †† a CPC containing formula (0.07%); ‡‡ a D-limonene (0.2%) and CPC (0.05%) containing formula; §§ a solution containing sodium fluoride (0.05%) and CPC (0.075%); *** a solution containing CHX (0.12%) and; ††† a CHX (0.2%) containing formula. ‡‡‡ As a control reaction, saline solution or excipient solution (water, glycerin, citric acid, colorant, sodium citrate) was used. Conclusion: Within the limitations of this study, we can conclude that a mouthwash containing both D-limonene and CPC reduced the virucidal activity in about 6 logs (>99.999% reduction). Hence, establishing a clinical protocol for dentists is suggested, where all patients to be treated rinse pre-operatively with a mouthwash containing both D-limonene and CPC to reduce the likelihood of infection with SARS-CoV-2 for dentists. This is a relatively inexpensive way to reduce viral transmission of SARS-CoV-2 from infected individuals within the community. It is also a simple way to decrease infections from asymptomatic and pre-symptomatic patients.
2021-12-30 2021 other research-article; Journal Article abstract-available Virucidal Activity of Different Mouthwashes Using a Novel Biochemical Assay Rodríguez-Casanovas H, la Rosa M, Bello-Lemus Y, Rasperini G, Acosta-Hoyos A. Healthcare (Basel). 2021; 10 (1)
Pathogenesis and Management of COVID-19.
Alfarouk KO, AlHoufie STS, Ahmed SBM, Shabana M, [...], Reshkin SJ.
J Xenobiot. 2021; 11 (2)
DOI: 10.3390/jox11020006
COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.
2021-05-21 2021 other review-article; Review; Journal Article abstract-available 10.3390/jox11020006 Pathogenesis and Management of COVID-19. Alfarouk KO, AlHoufie STS, Ahmed SBM, Shabana M, Ahmed A, Alqahtani SS, Alqahtani AS, Alqahtani AM, Ramadan AM, Ahmed ME, Ali HS, Bashir A, Devesa J, Cardone RA, Ibrahim ME, Schwartz L, Reshkin SJ. J Xenobiot. 2021; 11 (2)
Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2.
Palma M.
Germs. 2021; 11 (2)
DOI: 10.18683/germs.2021.1264
The current epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raising awareness of the need to act faster when dealing with new pathogens. Exposure to an emerging pathogen generates an antibody response that can be used for preventing and treating the infection. These antibodies might have a high specificity to a target, few side effects, and are useful in the absence of an effective vaccine for treating immunocompromised individuals. The approved antibodies against the receptor-binding domain (RBD) of the viral spike protein of SARS-CoV-2 (e.g., regdanvimab, bamlanivimab, etesevimab, and casirivimab/imdevimab) have been selected from the antibody repertoire of B cells from convalescent patients using flow cytometry, next-generation sequencing, and phage display. This encourages use of these techniques especially phage display, because it does not require expensive types of equipment and can be performed on the lab bench, thereby making it suitable for labs with limited resources. Also, the antibodies in blood samples from convalescent patients can be used to screen pre-made peptide libraries to identify epitopes for vaccine development. Different types of vaccines against SARS-CoV-2 have been developed, including inactivated virus vaccines, mRNA-based vaccines, non-replicating vector vaccines, and protein subunits. mRNA vaccines have numerous advantages over existing vaccines, such as efficacy, ease of manufacture, safety, and cost-effectiveness. Additionally, epitope vaccination may constitute an attractive strategy to induce high levels of antibodies against a pathogen and phages might be used as immunogenic carriers of such peptides. This is a point worth considering further, as phage-based vaccines have been shown to be safe in clinical trials and phages are easy to produce and tolerate high temperatures. In conclusion, identification of the antibody repertoire of recovering patients, and the epitopes they recognize, should be an attractive alternative option for developing therapeutic and prophylactic antibodies and vaccines against emerging pathogens.
2021-06-02 2021 other review-article; Review; Journal Article abstract-available 10.18683/germs.2021.1264 Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2. Palma M. Germs. 2021; 11 (2)
Treatment and research lines for the patient with COVID-19. What do we have and where are we going?
Gotera C.
Int Braz J Urol. 2020; 46 (suppl.1)
DOI: 10.1590/s1677-5538.ibju.2020.s118
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.
2020-07-01 2020 other review-article; Review; Journal Article abstract-available 10.1590/s1677-5538.ibju.2020.s118 Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Gotera C. Int Braz J Urol. 2020; 46 (suppl.1)
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.
Osuchowski MF, Winkler MS, Skirecki T, Cajander S, [...], Rubio I.
Lancet Respir Med. 2021; 9 (6)
DOI: 10.1016/s2213-2600(21)00218-6
The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
2021-05-06 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/s2213-2600(21)00218-6 The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM, Weis S, Garcia-Salido A, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohé SB, Wiersinga WJ, Almansa R, de la Fuente A, Martin-Loeches I, Meisel C, Spinetti T, Schefold JC, Cilloniz C, Torres A, Giamarellos-Bourboulis EJ, Ferrer R, Girardis M, Cossarizza A, Netea MG, van der Poll T, Bermejo-Martín JF, Rubio I. Lancet Respir Med. 2021; 9 (6)
Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro.
Silva RC, Freitas HF, Campos JM, Kimani NM, [...], Santos CBR.
Int J Mol Sci. 2021; 22 (21)
DOI: 10.3390/ijms222111739
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil's semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARS-CoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.
2021-10-29 2021 other research-article; Journal Article abstract-available 10.3390/ijms222111739 Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro. Silva RC, Freitas HF, Campos JM, Kimani NM, Silva CHTP, Borges RS, Pita SSR, Santos CBR. Int J Mol Sci. 2021; 22 (21)
COVID-19 pandemic: lessons learned from more than a century of pandemics and current vaccine development for pandemic control.
Buchy P, Buisson Y, Cintra O, Dwyer DE, [...], Petersen E.
Int J Infect Dis. 2021; 112
DOI: 10.1016/j.ijid.2021.09.045
Pandemic dynamics and health care responses are markedly different during the COVID-19 pandemic than in earlier outbreaks. Compared with established infectious disease such as influenza, we currently know relatively little about the origin, reservoir, cross-species transmission and evolution of SARS-CoV-2. Health care services, drug availability, laboratory testing, research capacity and global governance are more advanced than during 20th century pandemics, although COVID-19 has highlighted significant gaps. The risk of zoonotic transmission and an associated new pandemic is rising substantially. COVID-19 vaccine development has been done at unprecedented speed, with the usual sequential steps done in parallel. The pandemic has illustrated the feasibility of this approach and the benefits of a globally coordinated response and infrastructure. Some of the COVID-19 vaccines recently developed or currently in development might offer flexibility or sufficiently broad protection to swiftly respond to antigenic drift or emergence of new coronaviruses. Yet many challenges remain, including the large-scale production of sufficient quantity of vaccines, delivery of vaccines to all countries and ensuring vaccination of relevant age groups. This wide vaccine technology approach will be best employed in tandem with active surveillance for emerging variants or new pathogens using antigen mapping, metagenomics and next generation sequencing.
2021-09-23 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.ijid.2021.09.045 COVID-19 pandemic: lessons learned from more than a century of pandemics and current vaccine development for pandemic control. Buchy P, Buisson Y, Cintra O, Dwyer DE, Nissen M, Ortiz de Lejarazu R, Petersen E. Int J Infect Dis. 2021; 112
Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets.
Altable M, de la Serna JM.
Virus Res. 2021; 299
DOI: 10.1016/j.virusres.2021.198347

Background

There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. MAIN: SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signalling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed.

Conclusion

Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.
2021-02-22 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.virusres.2021.198347 Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets. Altable M, de la Serna JM. Virus Res. 2021; 299
Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation.
Rolfo C, Meshulami N, Russo A, Krammer F, [...], Hirsch FR.
J Thorac Oncol. 2021;
DOI: 10.1016/j.jtho.2021.11.001
Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.
2021-11-10 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.jtho.2021.11.001 Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation. Rolfo C, Meshulami N, Russo A, Krammer F, García-Sastre A, Mack PC, Gomez JE, Bhardwaj N, Benyounes A, Sirera R, Moore A, Rohs N, Henschke CI, Yankelevitz D, King J, Shyr Y, Bunn PA, Minna JD, Hirsch FR. J Thorac Oncol. 2021;
Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy.
Qaisrani MN, Belousov R, Rehman JU, Goliaei EM, [...], Roldán É.
Eur Phys J E Soft Matter. 2021; 44 (11)
DOI: 10.1140/epje/s10189-021-00137-3
Understanding the physical and chemical properties of viral infections at molecular scales is a major challenge for the scientific community more so with the outbreak of global pandemics. There is currently a lot of effort being placed in identifying molecules that could act as putative drugs or blockers of viral molecules. In this work, we computationally explore the importance in antiviral activity of a less studied class of molecules, namely surfactants. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the phospholipid lecithin (POPC), in water. Our microsecond simulations show a preferential binding of lecithin to the receptor-binding motif of SARS-CoV-2 with binding free energies significantly larger than [Formula: see text]. Furthermore, hydrophobic interactions involving lecithin non-polar tails dominate these binding events, which are also accompanied by dewetting of the receptor binding motif. Through an analysis of fluctuations in the radius of gyration of the receptor-binding domain, its contact maps with lecithin molecules, and distributions of water molecules near the binding region, we elucidate molecular interactions that may play an important role in interactions involving surfactant-type molecules and viruses. We discuss our minimal computational model in the context of lecithin-based liposomal nasal sprays as putative mitigating therapies for COVID-19.
2021-10-30 2021 other research-article; Journal Article abstract-available 10.1140/epje/s10189-021-00137-3 Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy. Qaisrani MN, Belousov R, Rehman JU, Goliaei EM, Girotto I, Franklin-Mergarejo R, Güell O, Hassanali A, Roldán É. Eur Phys J E Soft Matter. 2021; 44 (11)
Scientific evidence in the COVID-19 treatment: A comprehensive review.
Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P.
World J Virol. 2021; 10 (5)
DOI: 10.5501/wjv.v10.i5.217
In December 2019, cases of unknown origin pneumonia appeared in Wuhan, China; the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). According to the clinical severity, symptoms and response to the different treatments, the evolution of the disease is divided in three phases. We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective. In the viral phase, remdesivir has demonstrated reduction in recovery time but no mortality reduction. Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective. In the inflammatory phase, corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen, establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients. There are other immunosuppressive and immunomodulatory treatments such as anakinra, sarilumab, tocilizumab, colchicine or baricitinib that are being studied. Other treatments that were proposed at the beginning, like hydroxichloroquine or azithromycin, demonstrated no efficacy and increased mortality when combined.
2021-09-01 2021 other review-article; Review; Journal Article abstract-available 10.5501/wjv.v10.i5.217 Scientific evidence in the COVID-19 treatment: A comprehensive review. Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P. World J Virol. 2021; 10 (5)
Single-cell RNA sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium.
Vilella F, Wang W, Moreno I, Roson B, [...], Simon C.
Hum Reprod. 2021; 36 (10)
DOI: 10.1093/humrep/deab183

Study question

Are SARS-CoV-2 canonical cell entry machinery, consisting of ACE2, TMPRSS2, NRP1 and LY6E, or alternative potential cell entry machinery, consisting of BSG, ANPEP, CD209, CLEC4G, TMPRSS4, TMPRSS11A, FURIN, CTSB, CTSL and IFITM1, expressed in the human endometrium across the menstrual cycle?

Summary answer

Analysis of cell entry factors for SARS-CoV-2 by single-cell RNA-sequencing (scRNAseq) in the preconceptional human endometrium reveals low risk of infection.

What is known already

Gene expression datasets from bulk endometrial tissue show no significant expression of the SARS-CoV-2 receptor ACE2 and TMPRSS2. This is in contrast to reported expression of ACE2 at the single-cell level in the decidua and trophoblast cells at the maternal-fetal interface in early pregnancy, as well as vertical transmission of SARS-CoV-2 during pregnancy.

Study design, size, duration

This analysis of SARS-CoV-2 cell entry machinery gene expression was conducted by scRNAseq in 73 181 human endometrial cells isolated from endometrial biopsies obtained from 27 donors across the menstrual cycle.

Participants/materials, setting, methods

ScRNAseq examined the expression of genes encoding cell entry machinery for SARS-CoV-2. The raw data were from a previously published dataset.

Main results and the role of chance

ScRNAseq analysis showed no significant expression of ACE2 in stromal or unciliated epithelial cells in any phase of the menstrual cycle. TMPRSS2 was expressed in epithelial cells during the early proliferative and mid-secretory phases. Interestingly, the expression of NRP1 was observed in both stromal and epithelial cells across all phases of the menstrual cycle, and LY6E was highly expressed in stromal cells. In the mid-secretory phase, coexpression of ACE2 and TMPRSS2 was detected in 0.07% of luminal epithelial cells. No cells simultaneously expressed ACE2, NRP1 and TMPRSS2 at the time of embryo implantation. Focusing on non-canonical cell entry machinery, BSG was highly expressed in all cell types across the menstrual cycle and may interact with CTSB or CTSL proteases, but viral infection using this machinery has not yet been confirmed.

Large scale data

All raw data in this study can be found at NCBI's Gene Expression Omnibus (series accession code GSE111976) and Sequence Read Archive (accession code SRP135922).

Limitations, reasons for caution

Our findings at the single-cell level imply low efficiency of SARS-CoV-2 endometrial infection using canonical receptors in a cohort of healthy reproductive-age women; however, infection of endometrial cells can only be assessed in the presence of the virus. All samples were processed for scRNAseq, so no samples are remaining to analyze protein expression or spatial transcriptomics.

Wider implications of the findings

Our results offer a useful resource to guide reproductive decisions when assessing risk of endometrial infection by SARS-CoV-2 during the preconceptional period in asymptomatic COVID-19 carriers.

Study funding/competing interest(s)

This study was jointly supported by the March of Dimes, Chan Zuckerberg Biohub and MINECO/FEDER (SAF-2015-67164-R, to C.S.) (Spanish Government), and the European Union's Horizon 2020 Framework Programme for Research and Innovation (Grant agreement 874867). W.W. was supported by the Stanford Bio-X Graduate Bowes Fellowship and Chan Zuckerberg Biohub. F.V. was supported by the Miguel Servet Program Type II of ISCIII (CPII18/00020) and the FIS project (PI18/00957). A patent disclosure has been filed for the study with the title 'Methods for assessing endometrial transformation' and the global patent number 'EP 3807648 A2' under the inventors S.R.Q., C.S., W.W. and F.V. C.S. is the Founder and Head of the Scientific Advisory Board of Igenomix SL. S.R.Q is the Director of Mirvie. I.M. is partially employed by Igenomix SL. B.R. has no interests to declare.
2021-09-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/humrep/deab183 Single-cell RNA sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium. Vilella F, Wang W, Moreno I, Roson B, Quake SR, Simon C. Hum Reprod. 2021; 36 (10)
Subacute thyroiditis following COVID-19 infection.
de la Higuera López-Frías M, Perdomo CM, Galofré JC.
Rev Clin Esp (Barc). 2021; 221 (6)
DOI: 10.1016/j.rceng.2021.01.002
2021-03-26 2021 other Letter; Comment 10.1016/j.rceng.2021.01.002 Subacute thyroiditis following COVID-19 infection. de la Higuera López-Frías M, Perdomo CM, Galofré JC. Rev Clin Esp (Barc). 2021; 221 (6)
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19).
Domingo P, Mur I, Pomar V, Corominas H, [...], de Benito N.
EBioMedicine. 2020; 58
DOI: 10.1016/j.ebiom.2020.102887
The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.
2020-07-29 2020 fondo-covid review-article; Review; Journal Article abstract-available 10.1016/j.ebiom.2020.102887 The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19). Domingo P, Mur I, Pomar V, Corominas H, Casademont J, de Benito N. EBioMedicine. 2020; 58
Living evidence for SARS-CoV-2.
Santillan-Garcia A.
Med Intensiva (Engl Ed). 2021; 45 (5)
DOI: 10.1016/j.medine.2021.04.003
2021-04-30 2021 other Letter 10.1016/j.medine.2021.04.003 Living evidence for SARS-CoV-2. Santillan-Garcia A. Med Intensiva (Engl Ed). 2021; 45 (5)
A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD-ACE2 Interaction.
Fernandez-Fuentes N, Molina R, Oliva B.
Int J Mol Sci. 2021; 22 (21)
DOI: 10.3390/ijms222111627
The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.
2021-10-27 2021 other research-article; Journal Article abstract-available 10.3390/ijms222111627 A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD-ACE2 Interaction. Fernandez-Fuentes N, Molina R, Oliva B. Int J Mol Sci. 2021; 22 (21)
Plasma ACE2 species are differentially altered in COVID-19 patients.
García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, [...], Sáez-Valero J.
FASEB J. 2021; 35 (8)
DOI: 10.1096/fj.202100051r
Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.
2021-08-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1096/fj.202100051r Plasma ACE2 species are differentially altered in COVID-19 patients. García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, Cortés-Gómez MÁ, Brinkmalm G, Andrés M, León-Ramírez JM, Boix V, Gil J, Zetterberg H, Esteban M, Merino E, Sáez-Valero J. FASEB J. 2021; 35 (8)
Acute and Chronic Effects of COVID-19 on the Cardiovascular System.
Arévalos V, Ortega-Paz L, Rodríguez-Arias JJ, Calvo López M, [...], Brugaletta S.
J Cardiovasc Dev Dis. 2021; 8 (10)
DOI: 10.3390/jcdd8100128
COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20%. Its presence is related to worse clinical outcomes and in-hospital mortality. The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified. The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies, with a striking incidence of imaging criteria for myocarditis. Regarding post-acute and chronic follow-up results, the persistence of symptoms and imaging changes in recovered COVID-19 patients has raised concerns about the duration and the possible significance of these findings. Even though the knowledge about this disease has increased incredibly in the last year, many aspects are still unclear and warrant further research.
2021-10-05 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcdd8100128 Acute and Chronic Effects of COVID-19 on the Cardiovascular System. Arévalos V, Ortega-Paz L, Rodríguez-Arias JJ, Calvo López M, Castrillo-Golvano L, Salazar-Rodríguez A, Sabaté-Tormos M, Spione F, Sabaté M, Brugaletta S. J Cardiovasc Dev Dis. 2021; 8 (10)
Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort.
Rodríguez-Díaz M, Alonso-Molero J, Cabero-Perez MJ, Llorca J, [...], The Moacc-Group.
Int J Environ Res Public Health. 2021; 18 (20)
DOI: 10.3390/ijerph182010931
The new coronavirus, SARS-CoV-2, is devastating for specific groups of patients, but currently there is not enough information concerning its effects on pregnant women. The purpose of this study is to identify the impact of SARS-CoV-2 infection on pregnancy and the consequences that it could cause. We studied a cohort of pregnant ladies who were tested for SARS-CoV-2 infection by RT-PCR and classified as infected or not infected. The recruitment was carried out in the HUMV hospital, a third-level hospital located in Santander, northern Spain. It started on 23 March 2020 and ended on 14 October 2020. Data from our cohort were compared to another cohort recruited in 2018 at the same hospital. We found that gestational hypertension, placental abruptio, and home exposure to an infected person, among other variables, could be associated with SARS-CoV-2 infection. In conclusion, we consider pregnant women a high-risk group of patients towards a possible SARS-CoV-2 infection, especially those who present with conditions such as gestational hypertension or obesity; moreover, we think that SARS-CoV-2 infection could increase the possibilities of having an abruptio placentae, although this result was found in only a few women, so it requires further confirmation.
2021-10-18 2021 other research-article; Journal Article abstract-available 10.3390/ijerph182010931 Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort. Rodríguez-Díaz M, Alonso-Molero J, Cabero-Perez MJ, Llorca J, Dierssen-Sotos T, Gómez-Acebo I, The Moacc-Group. Int J Environ Res Public Health. 2021; 18 (20)
Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.
Mabrouk MT, Chiem K, Rujas E, Huang WC, [...], Lovell J.
Sci Adv. 2021; 7 (49)
DOI: 10.1126/sciadv.abj1476
[Figure: see text].
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1126/sciadv.abj1476 Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice. Mabrouk MT, Chiem K, Rujas E, Huang WC, Jahagirdar D, Quinn B, Surendran Nair M, Nissly RH, Cavener VS, Boyle NR, Sornberger TA, Kuchipudi SV, Ortega J, Julien JP, Martinez-Sobrido L, Lovell J. Sci Adv. 2021; 7 (49)
Histopathology features of the lung in COVID-19 patients.
Angeles Montero-Fernandez M, Pardo-Garcia R.
Diagn Histopathol (Oxf). 2021; 27 (3)
DOI: 10.1016/j.mpdhp.2020.11.009
COVID-19 is the infectious disease caused by the recently discovered coronavirus, SARS-CoV-2, unknown before the outbreak in Wuhan, China, in December 2019. COVID-19 is a pandemic, infectious disease that has simultaneously affected many countries globally. The leading cause of dead in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). Diffuse alveolar damage (DAD) is the histopathological pattern commonly described in all the postmortem series up to date. DAD is divided into two phases, and depending on the length of the disease, the morphological features seen in the specimens vary. There is an acute/exudative phase, which occurs during the first week after the pulmonary injury, following by the organizing/proliferative phase. Additional features detailed include vascular thrombosis, endothelialitis and angiogenesis. Interestingly, there is an ongoing discussion about the specificity of these changes, as diffuse alveolar damage seen in other viral infections show similar features.
2020-12-04 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.mpdhp.2020.11.009 Histopathology features of the lung in COVID-19 patients. Angeles Montero-Fernandez M, Pardo-Garcia R. Diagn Histopathol (Oxf). 2021; 27 (3)
SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.
Ferreira G, Santander A, Savio F, Guirado M, [...], Nicolson GL.
Biochim Biophys Acta Mol Basis Dis. 2021; 1867 (12)
DOI: 10.1016/j.bbadis.2021.166264
The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.
2021-09-03 2021 other Historical Article; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.bbadis.2021.166264 SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases. Ferreira G, Santander A, Savio F, Guirado M, Sobrevia L, Nicolson GL. Biochim Biophys Acta Mol Basis Dis. 2021; 1867 (12)
Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency.
Cabañero-Navalon MD, Garcia-Bustos V, Ruiz-Rodriguez P, Comas I, [...], Moral PM.
Clin Microbiol Infect. 2021;
DOI: 10.1016/j.cmi.2021.10.021
2021-11-10 2021 other Letter 10.1016/j.cmi.2021.10.021 Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency. Cabañero-Navalon MD, Garcia-Bustos V, Ruiz-Rodriguez P, Comas I, Coscollá M, Martinez-Priego L, Todolí J, Moral PM. Clin Microbiol Infect. 2021;
Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus.
Martinez MA.
Antimicrob Agents Chemother. 2020; 64 (5)
DOI: 10.1128/aac.00399-20
Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.
2020-04-21 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1128/aac.00399-20 Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Martinez MA. Antimicrob Agents Chemother. 2020; 64 (5)
A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis.
González-Domenech CM, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, [...], Santos J.
Viruses. 2021; 13 (5)
DOI: 10.3390/v13050931
By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.
2021-05-17 2021 other review-article; Review; Journal Article abstract-available 10.3390/v13050931 A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and <i>Mycobacterium tuberculosis</i>. González-Domenech CM, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, Palacios-Muñoz R, Santos J. Viruses. 2021; 13 (5)
Immunological imprinting of the antibody response in COVID-19 patients.
Aydillo T, Rombauts A, Stadlbauer D, Aslam S, [...], García-Sastre A.
Nat Commun. 2021; 12 (1)
DOI: 10.1038/s41467-021-23977-1
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
2021-06-18 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1038/s41467-021-23977-1 Immunological imprinting of the antibody response in COVID-19 patients. Aydillo T, Rombauts A, Stadlbauer D, Aslam S, Abelenda-Alonso G, Escalera A, Amanat F, Jiang K, Krammer F, Carratala J, García-Sastre A. Nat Commun. 2021; 12 (1)
The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy.
Ramos E, López-Muñoz F, Gil-Martín E, Egea J, [...], Romero A.
Antioxidants (Basel). 2021; 10 (7)
DOI: 10.3390/antiox10071152
Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.
2021-07-20 2021 other review-article; Review; Journal Article abstract-available 10.3390/antiox10071152 The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy. Ramos E, López-Muñoz F, Gil-Martín E, Egea J, Álvarez-Merz I, Painuli S, Semwal P, Martins N, Hernández-Guijo JM, Romero A. Antioxidants (Basel). 2021; 10 (7)
Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.
Dobaño C, Alonso S, Fernández de Sevilla M, Vidal M, [...], Jordan I.
BMC Med. 2021; 19 (1)
DOI: 10.1186/s12916-021-02184-1

Background

Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach.

Methods

Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020.

Results

Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19.

Conclusion

Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics.
2021-11-23 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s12916-021-02184-1 Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain. Dobaño C, Alonso S, Fernández de Sevilla M, Vidal M, Jiménez A, Pons Tomas G, Jairoce C, Melé Casas M, Rubio R, Hernández García M, Ruiz-Olalla G, Girona-Alarcón M, Barrios D, Santano R, Mitchell RA, Puyol L, Mayer L, Chi J, Rodrigo Melero N, Carolis C, Garcia-Miquel A, Bonet-Carne E, Claverol J, Cubells M, Fortuny C, Fumadó V, Jou C, Muñoz-Almagro C, Izquierdo L, Bassat Q, Gratacós E, Aguilar R, García-García JJ, Moncunill G, Jordan I. BMC Med. 2021; 19 (1)
The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses.
Chaisuwan W, Phimolsiripol Y, Chaiyaso T, Techapun C, [...], Seesuriyachan P.
Front Nutr. 2021; 8
DOI: 10.3389/fnut.2021.772033
Viral infections may cause serious human diseases. For instance, the recent appearance of the novel virus, SARS-CoV-2, causing COVID-19, has spread globally and is a serious public health concern. The consumption of healthy, proper, functional, and nutrient-rich foods has an important role in enhancing an individual's immune system and preventing viral infections. Several polysaccharides from natural sources such as algae, bacteria, and fungi have been considered as generally recognized as safe (GRAS) by the US Food and Drug Administration. They are safe, low-toxicity, biodegradable, and have biological activities. In this review, the bioactive polysaccharides derived from various microorganisms, including bacteria, fungi, and algae were evaluated. Antiviral mechanisms of these polysaccharides were discussed. Finally, the potential use of microbial and algal polysaccharides as an antiviral and immune boosting strategy was addressed. The microbial polysaccharides exhibited several bioactivities, including antioxidant, anti-inflammatory, antimicrobial, antitumor, and immunomodulatory activities. Some microbes are able to produce sulfated polysaccharides, which are well-known to exert a board spectrum of biological activities, especially antiviral properties. Microbial polysaccharide can inhibit various viruses using different mechanisms. Furthermore, these microbial polysaccharides are also able to modulate immune responses to prevent and/or inhibit virus infections. There are many molecular factors influencing their bioactivities, e.g., functional groups, conformations, compositions, and molecular weight. At this stage of development, microbial polysaccharides will be used as adjuvants, nutrient supplements, and for drug delivery to prevent several virus infections, especially SARS-CoV-2 infection.
2021-11-05 2021 other review-article; Review; Journal Article abstract-available 10.3389/fnut.2021.772033 The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses. Chaisuwan W, Phimolsiripol Y, Chaiyaso T, Techapun C, Leksawasdi N, Jantanasakulwong K, Rachtanapun P, Wangtueai S, Sommano SR, You S, Regenstein JM, Barba FJ, Seesuriyachan P. Front Nutr. 2021; 8
Large-scale study on virological and serological prevalence of SARS-CoV-2 in cats and dogs in Spain.
Barroso-Arévalo S, Barneto A, Ramos ÁM, Rivera B, [...], Sánchez-Vizcaíno JM.
Transbound Emerg Dis. 2021;
DOI: 10.1111/tbed.14366
The disease produced by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is currently one of the primary concerns worldwide. Knowing the zoonotic origin of the disease and that several animal species, including dogs and cats, are susceptible to viral infection, it is critical to assess the relevance of pets in this pandemic. Here, we performed a large-scale study on SARS-CoV-2 serological and viral prevalence in cats and dogs in Spain in order to elucidate their role and susceptibility. Samples from animals in contact with COVID-19 positive people and/or compatible symptoms (n = 492), as well as from random animals (n = 1024), were taken. Despite the large number of animals analyzed, only 12 animals (eight dogs and four cats), which represents 0.79% of the total analyzed animals (n = 1516), were positive for viral SARS-CoV-2 RNA detection by reverse transcription quantitative PCR (RT-qPCR) in which viral isolation was possible in four animals. We detected neutralizing antibodies in 34 animals, four of them were also positive for PCR. This study evidences that pets are susceptible to SARS-CoV-2 infection in natural conditions but at a low level, as evidenced by the low percentage of positive animals detected, being infected humans the main source of infection. However, the inclusion of animals in the surveillance of COVID-19 is still recommended.
2021-11-01 2021 fondo-covid research-article; Journal Article abstract-available 10.1111/tbed.14366 Large-scale study on virological and serological prevalence of SARS-CoV-2 in cats and dogs in Spain. Barroso-Arévalo S, Barneto A, Ramos ÁM, Rivera B, Sánchez R, Sánchez-Morales L, Pérez-Sancho M, Buendía A, Ferreras E, Ortiz-Menéndez JC, Moreno I, Serres C, Vela C, Risalde MÁ, Domínguez L, Sánchez-Vizcaíno JM. Transbound Emerg Dis. 2021;
Characteristics of patients with suspected COVID-19 pneumonia and repeatedly negative RT-PCR.
Navarro-Carrera P, Roces-Álvarez P, Ramos-Ramos JC, Montero D, [...], García Bujalance S.
Access Microbiol. 2021; 3 (12)
DOI: 10.1099/acmi.0.000279

Objectives

Challenges remain and there are still a sufficient number of cases with epidemiological, clinical features and radiological data suggestive of COVID-19 pneumonia that persist negative in their RT-PCR results. The aim of the study was to define the distinguishing characteristics between patients developing a serological response to SARS-CoV-2 and those who did not.

Methods

RT-PCR tests used were TaqPath 2019-nCoV Assay Kit v1 (ORF-1ab, N and S genes) from Thermo Fisher Diagnostics and SARS-COV-2 Kit (N and E genes) from Vircell. Serological response was tested using the rapid SARS-CoV2 IgG/IgM Test Cassette from T and D Diagnostics Canada and CMC Medical Devices and Drugs, S.L, CE.

Results

In this cross-sectional study, we included a cohort of 52 patients recruited from 31 March 2020 to 23 April 2020. Patients with positive serology had an older average age (73.29) compared to those who were negative (54.82) (P<0.05). Sat02 in 27 of 34 patients with positive serology were below 94% (P<0.05). There was a frequency of 1.5% negative SARS-CoV-2 RT-PCRs during the study period concurring with 36.7% of positivity.

Conclusion

Clinical features and other biomarkers in a context of a positive serology can be considered crucial for diagnosis.
2021-12-13 2021 other research-article; Journal Article abstract-available 10.1099/acmi.0.000279 Characteristics of patients with suspected COVID-19 pneumonia and repeatedly negative RT-PCR. Navarro-Carrera P, Roces-Álvarez P, Ramos-Ramos JC, Montero D, Losantos I, Díaz-Pollán B, García Bujalance S. Access Microbiol. 2021; 3 (12)
Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases.
Baiges A, Cerda E, Amicone C, Téllez L, [...], García-Pagán JC.
Clin Gastroenterol Hepatol. 2021;
DOI: 10.1016/j.cgh.2021.12.032

Background & aims

Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival.

Methods

This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included.

Results

Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality.

Conclusions

Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.
2021-12-27 2021 other research-article; Journal Article abstract-available 10.1016/j.cgh.2021.12.032 Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases. Baiges A, Cerda E, Amicone C, Téllez L, Alvarado-Tapias E, Puente A, Fortea JI, Llop E, Rocha F, Orts L, Ros-Fargas O, Vizcarra P, Zekrini K, Lounes OA, Touati G, Jimenez N, Serrano MJ, Falgà A, Magaz M, Olivas P, Betancourt F, Perez-Campuzano V, Turon F, Payance A, Goria O, Rautou PE, Hernández-Gea V, Villanueva C, Albillos A, Plessier A, García-Pagán JC. Clin Gastroenterol Hepatol. 2021;
Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects.
Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M.
World J Hepatol. 2021; 13 (10)
DOI: 10.4254/wjh.v13.i10.1299
The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.
2021-10-01 2021 other review-article; Review; Journal Article abstract-available 10.4254/wjh.v13.i10.1299 Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects. Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M. World J Hepatol. 2021; 13 (10)
Comparative study of different SARS-CoV-2 diagnostic techniques.
Vallejo L, Martínez-Rodríguez M, Nieto-Bazán MJ, Delgado-Iribarren A, [...], Culebras E.
J Virol Methods. 2021; 298
DOI: 10.1016/j.jviromet.2021.114281
The rapid spread of SARS-CoV-2 led to the necessity of developing diagnostic tests for rapid virus detection. Many commercial platforms have appeared and have been approved for this purpose. In this study, 95 positive and 5 negative retrospective samples were analyzed by 4 different commercial RT-qPCR kits (TaqMan 2019nCoV Assay, Allplex™SARS-COV-2 Assay, FTD SARS-COV-2 Assay and qCOVID-19). The Hologic Aptima SARS-COV-2 and the Clart-COVID-19 system were also tested. serial dilutions of SARS-COV-2 standard control were included for sensitivity analysis. Among the qPCR tested qCOVID19 and Allplex™SARS-COV-2 Assay were both able to detect all the clinical samples included in the study. All four qPCR evaluated showed high sensitivity for samples with Ct<33. Clart-COVID-19 microarrays detected all samples and controls used in this study whereas Hologic Aptima Panther failed with one of the clinical samples. However, the main problem with this system was the number of invalidated samples despite avoiding the use of medium with guanidine isothiocyanate as recommended by the manufacturer. All the techniques tested were of value for SARS-CoV-2 detection.
2021-09-13 2021 other research-article; Journal Article abstract-available 10.1016/j.jviromet.2021.114281 Comparative study of different SARS-CoV-2 diagnostic techniques. Vallejo L, Martínez-Rodríguez M, Nieto-Bazán MJ, Delgado-Iribarren A, Culebras E. J Virol Methods. 2021; 298
Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications.
García-Salido A.
An Pediatr (Engl Ed). 2020; 93 (1)
DOI: 10.1016/j.anpede.2020.04.006
The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV-2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and its applicability to SARS-CoV-2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.
2020-06-08 2020 other research-article; Journal Article abstract-available 10.1016/j.anpede.2020.04.006 Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications. García-Salido A. An Pediatr (Engl Ed). 2020; 93 (1)
Innate cell response in severe SARS-CoV-2 infection in children: Expression analysis of CD64, CD18 and CD11a.
García-Salido A, García-Teresa MÁ, Leoz-Gordillo I, Martínez de Azagra-Garde A, [...], Ramirez-Orellana M.
Med Intensiva (Engl Ed). 2022; 46 (1)
DOI: 10.1016/j.medine.2020.09.008
2022-01-01 2022 other Case Reports; case-report 10.1016/j.medine.2020.09.008 Innate cell response in severe SARS-CoV-2 infection in children: Expression analysis of CD64, CD18 and CD11a. García-Salido A, García-Teresa MÁ, Leoz-Gordillo I, Martínez de Azagra-Garde A, Cabrero-Hernández M, Ramirez-Orellana M. Med Intensiva (Engl Ed). 2022; 46 (1)
Plitidepsin: a Repurposed Drug for the Treatment of COVID-19.
Martinez MA.
Antimicrob Agents Chemother. 2021; 65 (4)
DOI: 10.1128/aac.00200-21
Finding antivirals to reduce coronavirus disease 2019 (COVID-19) morbidity and mortality has been challenging. Large randomized clinical trials that aimed to test four repurposed drugs, hydroxychloroquine, lopinavir-ritonavir, interferon beta 1a, and remdesivir, have shown that these compounds lack an impact on the COVID-19 course. Although the phase III COVID-19 vaccine trial results are encouraging, the search for effective COVID-19 therapeutics should not stop. Recently, plitidepsin (aplidin) demonstrated highly effective preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antiviral activity was 27.5-fold more potent than that of remdesivir (K. M. White, R. Rosales, S. Yildiz, T. Kehrer, et al., Science, 2021, https://science.sciencemag.org/content/early/2021/01/22/science.abf4058). Plitidepsin, a repurposed drug developed for the treatment of multiple myeloma, targets the host translation cofactor eEF1A. Plitidepsin has shown efficacy in animal models and phase I/II human trials. Although plitidepsin is administered intravenously and its toxicity profile remains to be fully characterized, this compound may be a promising alternative COVID-19 therapeutic.
2021-03-18 2021 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1128/aac.00200-21 Plitidepsin: a Repurposed Drug for the Treatment of COVID-19. Martinez MA. Antimicrob Agents Chemother. 2021; 65 (4)
Respiratory co-and superinfections in COVID-19.
Del Pozo JL.
Rev Esp Quimioter. 2021; 34 Suppl 1
DOI: 10.37201/req/s01.20.2021
There are few publications on the impact of coinfection and superinfection in patients with COVID-19. Patients with higher severity are much more prone to secondary bacterial, fungal or viral infections. The overuse of antimicrobials in many viral infections (including SARS-CoV-2 infections) undoubtedly contributes to the current antimicrobial resistance crisis. In the context of COVID-19, we are witnessing an increase in multidrug-resistant bacterial infections in our hospitals. The heterogeneity of published studies makes it critical to perform more large-scale studies to better understand the pathogenesis of coinfections or superinfections in the COVID-19 patient.
2021-09-30 2021 other research-article; Review; Journal Article abstract-available 10.37201/req/s01.20.2021 Respiratory co-and superinfections in COVID-19. Del Pozo JL. Rev Esp Quimioter. 2021; 34 Suppl 1
Emerging therapies for COVID-19 pneumonia.
Battaglini D, Robba C, Ball L, Cruz FF, [...], Rocco PRM.
Expert Opin Investig Drugs. 2020; 29 (7)
DOI: 10.1080/13543784.2020.1771694
2020-06-01 2020 other Editorial 10.1080/13543784.2020.1771694 Emerging therapies for COVID-19 pneumonia. Battaglini D, Robba C, Ball L, Cruz FF, Silva PL, Pelosi P, Rocco PRM. Expert Opin Investig Drugs. 2020; 29 (7)
Spatial and temporal distribution of SARS-CoV-2 diversity circulating in wastewater.
Pérez-Cataluña A, Chiner-Oms Á, Cuevas-Ferrando E, Díaz-Reolid A, [...], Sánchez G.
Water Res. 2021; 211
DOI: 10.1016/j.watres.2021.118007
Wastewater-based epidemiology (WBE) has proven to be an effective tool for epidemiological surveillance of SARS-CoV-2 during the current COVID-19 pandemic. Furthermore, combining WBE together with high-throughput sequencing techniques can be useful for the analysis of SARS-CoV-2 viral diversity present in a given sample. The present study focuses on the genomic analysis of SARS-CoV-2 in 76 sewage samples collected during the three epidemiological waves that occurred in Spain from 14 wastewater treatment plants distributed throughout the country. The results obtained demonstrate that the metagenomic analysis of SARS-CoV-2 in wastewater allows the detection of mutations that define the B.1.1.7 lineage and the ability of the technique to anticipate the detection of certain mutations before they are detected in clinical samples. The study proves the usefulness of sewage sequencing to track Variants of Concern that can complement clinical testing to help in decision-making and in the analysis of the evolution of the pandemic.
2021-12-24 2021 other research-article; Journal Article abstract-available 10.1016/j.watres.2021.118007 Spatial and temporal distribution of SARS-CoV-2 diversity circulating in wastewater. Pérez-Cataluña A, Chiner-Oms Á, Cuevas-Ferrando E, Díaz-Reolid A, Falcó I, Randazzo W, Girón-Guzmán I, Allende A, Bracho MA, Comas I, Sánchez G. Water Res. 2021; 211
Vitamin D Endocrine System and COVID-19.
Bouillon R, Quesada-Gomez JM.
JBMR Plus. 2021; 5 (12)
DOI: 10.1002/jbm4.10576
Preclinical data strongly suggest that the vitamin D endocrine system (VDES) may have extraskeletal effects. Cells of the immune and cardiovascular systems and lungs can express the vitamin D receptor, and overall these cells respond in a coherent fashion when exposed to 1,25-dihydroxyvitamin D, the main metabolite of the VDES. Supplementation of vitamin D-deficient subjects may decrease the risk of upper respiratory infections. The VDES also has broad anti-inflammatory and anti-thrombotic effects, and other mechanisms argue for a potential beneficial effect of a good vitamin D status on acute respiratory distress syndrome, a major complication of this SARS-2/COVID-19 infection. Activation of the VDES may thus have beneficial effects on the severity of COVID-19. Meta-analysis of observational data show that a better vitamin D status decreased the requirement of intensive care treatment or decreased mortality. A pilot study in Cordoba indicated that admission to intensive care was drastically reduced by administration of a high dose of calcifediol early after hospital admission for COVID-19. A large observational study in Barcelona confirmed that such therapy significantly decreased the odds ratio (OR) of mortality (OR = 0.52). This was also the conclusion of a retrospective study in five hospitals of Southern Spain. A retrospective study on all Andalusian patients hospitalized because of COVID-19, based on real-world data from the health care system, concluded that prescription of calcifediol (hazard ratio [HR] = 0.67) or vitamin D (HR = 0.75), 15 days before hospital admission decreased mortality within the first month. In conclusion, a good vitamin D status may have beneficial effects on the course of COVID-19. This needs to be confirmed by large, randomized trials, but in the meantime, we recommend (rapid) correction of 25 hydroxyvitamin D (25OHD) deficiency in subjects exposed to this coronavirus. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
2021-11-17 2021 other research-article; Journal Article abstract-available 10.1002/jbm4.10576 Vitamin D Endocrine System and COVID-19. Bouillon R, Quesada-Gomez JM. JBMR Plus. 2021; 5 (12)
The sharing of research data facing the COVID-19 pandemic.
Lucas-Dominguez R, Alonso-Arroyo A, Vidal-Infer A, Aleixandre-Benavent R.
Scientometrics. 2021;
DOI: 10.1007/s11192-021-03971-6
During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months.
2021-04-26 2021 other research-article; Journal Article abstract-available 10.1007/s11192-021-03971-6 The sharing of research data facing the COVID-19 pandemic. Lucas-Dominguez R, Alonso-Arroyo A, Vidal-Infer A, Aleixandre-Benavent R. Scientometrics. 2021;
Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019.
Rakislova N, Rodrigo-Calvo MT, Marimon L, Ribera-Cortada I, [...], Ordi J.
Clin Infect Dis. 2021; 73 (Suppl_5)
DOI: 10.1093/cid/ciab812

Background

Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure.

Methods

From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry.

Results

The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs.

Conclusions

MITS is useful for evaluating COVID-19-related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/cid/ciab812 Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019. Rakislova N, Rodrigo-Calvo MT, Marimon L, Ribera-Cortada I, Ismail MR, Carrilho C, Fernandes F, Ferrando M, Sanfeliu E, Castillo P, Guerrero J, Ramírez-Ruz J, Saez de Gordoa K, López Del Campo R, Bishop R, Ortiz E, Muñoz-Beatove A, Vila J, Hurtado JC, Navarro M, Maixenchs M, Delgado V, Aldecoa I, Martinez-Pozo A, Castro P, Menéndez C, Bassat Q, Martinez MJ, Ordi J. Clin Infect Dis. 2021; 73 (Suppl_5)
Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.
Veljkovic V, Vergara-Alert J, Segalés J, Paessler S.
F1000Res. 2020; 9
DOI: 10.12688/f1000research.22149.4
A novel coronavirus recently identified in Wuhan, China (SARS-CoV-2) has expanded the number of highly pathogenic coronaviruses affecting humans. The SARS-CoV-2 represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging SARS-CoV-2 is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of SARS-CoV-2; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the SARS-CoV-2, and that domain 288-330 of S1 protein from the SARS-CoV-2 represents promising therapeutic and/or vaccine target.
2020-01-27 2020 other brief-report; Journal Article abstract-available 10.12688/f1000research.22149.4 Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. F1000Res. 2020; 9
Identification, Mechanism, and Treatment of Skin Lesions in COVID-19: A Review.
Fernández-Lázaro D, Garrosa M.
Viruses. 2021; 13 (10)
DOI: 10.3390/v13101916
Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that primarily causes respiratory symptoms. However, an increasing number of cutaneous manifestations associated with this disease have been reported. The aim of this study is to analyze the scientific literature on cutaneous manifestations associated with SARS-CoV-2 by means of a narrative literature review until June 2021. The search was conducted in the following electronic databases: Medline (PubMed), SciELO, and Cochrane Library Plus. The most common cutaneous manifestations in patients with COVID-19 are vesicular eruptions, petechial/purpuric rashes, acral lesions, liveoid lesions, urticarial rash, and maculopapular-erythematous rash. These manifestations may be the first presenting symptoms of SARS-CoV-2 infection, as is the case with acral lesions, vesicular eruptions, and urticaria. In relation to severity, the presence of liveoid lesions may be associated with a more severe course of the disease. Treatment used for dermatological lesions includes therapy with anticoagulants, corticosteroids, and antihistamines. Knowledge of the dermatologic manifestations associated with SARS-CoV-2 contributes to the diagnosis of COVID-19 in patients with skin lesions associated with respiratory symptoms or in asymptomatic patients. In addition, understanding the dermatologic lesions associated with COVID-19 could be useful to establish a personalized care plan.
2021-09-24 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/v13101916 Identification, Mechanism, and Treatment of Skin Lesions in COVID-19: A Review. Fernández-Lázaro D, Garrosa M. Viruses. 2021; 13 (10)
SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression
Álvarez H, Ruiz-Mateos E, Juiz-González P, Vitallé J, [...], Llibre J.
Microorganisms. 2022; 10 (1)
DOI:
Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.
2022-01-01 2022 other Case Reports; case-report abstract-available SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression Álvarez H, Ruiz-Mateos E, Juiz-González P, Vitallé J, Viéitez I, Vázquez-Friol M, Torres-Beceiro I, Pérez-Gómez A, Gallego-García P, Estévez-Gómez N, De Chiara L, Poveda E, Posada D, Llibre J. Microorganisms. 2022; 10 (1)
Critical Presentation of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Report.
Massanella M, Martin-Urda A, Mateu L, Marín T, [...], Paredes R.
Open Forum Infect Dis. 2021; 8 (7)
DOI: 10.1093/ofid/ofab329

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections have been reported; however, most cases are milder than the primary infection. We report the first case of a life-threatening critical presentation of a SARS-CoV-2 reinfection.

Methods

A 62-year-old man from Palamós (Spain) suffered a first mild coronavirus disease 2019 (COVID-19) episode in March 2020, confirmed by 2 independent SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) assays and a normal radiograph. He recovered completely and tested negative on 2 consecutive PCRs. In August 2020, the patient developed a second SARS-CoV-2 infection with life-threatening bilateral pneumonia and Acute respiratory distress syndrome criteria, requiring COVID-19-specific treatment (remdesivir + dexamethasone) plus high-flow oxygen therapy. Nasopharyngeal swabs from the second episode were obtained for virus quantification by real-time PCR, for virus outgrowth and sequencing. In addition, plasma and peripheral blood mononuclear cells during the hospitalization period were used to determine SARS-CoV-2-specific humoral and T-cell responses.

Results

Genomic analysis of SARS-CoV-2 showed that the virus had probably originated shortly before symptom onset. When the reinfection occurred, the subject showed a weak immune response, with marginal humoral and specific T-cell responses against SARS-CoV-2. All antibody isotypes tested as well as SARS-CoV-2 neutralizing antibodies increased sharply after day 8 postsymptoms. A slight increase of T-cell responses was observed at day 19 after symptom onset.

Conclusions

The reinfection was firmly documented and occurred in the absence of robust preexisting humoral and cellular immunity. SARS-CoV-2 immunity in some subjects is unprotective and/or short-lived; therefore, SARS-CoV-2 vaccine schedules inducing long-term immunity will be required to bring the pandemic under control.
2021-06-23 2021 fondo-covid Case Reports; case-report abstract-available 10.1093/ofid/ofab329 Critical Presentation of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Report. Massanella M, Martin-Urda A, Mateu L, Marín T, Aldas I, Riveira-Muñoz E, Kipelainen A, Jiménez-Moyano E, Rodriguez de la Concepción ML, Avila-Nieto C, Trinité B, Pradenas E, Rodon J, Marfil S, Parera M, Carrillo J, Blanco J, Prado JG, Ballana E, Vergara-Alert J, Segalés J, Noguera-Julian M, Masabeu À, Clotet B, Toda MR, Paredes R. Open Forum Infect Dis. 2021; 8 (7)
Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2.
Calina D, Hernández AF, Hartung T, Egorov AM, [...], Docea AO.
Life (Basel). 2021; 11 (9)
DOI: 10.3390/life11090907
In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns.
2021-08-31 2021 other review-article; Review; Journal Article abstract-available 10.3390/life11090907 Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2. Calina D, Hernández AF, Hartung T, Egorov AM, Izotov BN, Nikolouzakis TK, Tsatsakis A, Vlachoyiannopoulos PG, Docea AO. Life (Basel). 2021; 11 (9)
What we know and what we need to know about the origin of SARS-CoV-2.
Domingo JL.
Environ Res. 2021; 200
DOI: 10.1016/j.envres.2021.111785
Since the appearance of the first cases of COVID-19 in 2019, an unprecedented number of documents on that disease have been published in a short space of time. The current available information covers a large number of topics related with COVID-19 and/or the coronavirus (SARS-CoV-2) responsible of the disease. However, only a limited number of publications have been focused on a controversial issue: the origin of the SARS-CoV-2. In this paper, the scientific literature on the origin of SARS-CoV-2 has been reviewed. Documents published during 2020 and 2021 (January 1-July 19) in journals that are indexed in PubMed and/or Scopus has been considered. The revised studies were grouped according to these two potential origins: natural and unnatural. The analyses of the conclusions of the different documents here assessed show that even considering the zoonotic hypothesis as the most likely, with bats and pangolins being possibly in the origin of the coronavirus, today's date the intermediate source species of SARS-CoV-2 has not been confirmed yet. On the other hand, some researchers point to an unnatural origin of this coronavirus, but their conclusions are not strongly supported by a clear scientific evidence. Given the tremendous severity of the current pandemic, investigations to establish clearly and definitively the origin of SARS-CoV-2, are basic and essential in order to prevent potential future pandemics of similar nature.
2021-07-28 2021 other research-article; Journal Article abstract-available 10.1016/j.envres.2021.111785 What we know and what we need to know about the origin of SARS-CoV-2. Domingo JL. Environ Res. 2021; 200
Volcanic Ash as a Precursor for SARS-CoV-2 Infection Among Susceptible Populations in Ecuador: A Satellite Imaging and Excess Mortality-Based Analysis.
Toulkeridis T, Seqqat R, Torres Arias M, Salazar-Martinez R, [...], Debut A.
Disaster Med Public Health Prep. 2021;
DOI: 10.1017/dmp.2021.154
The global coronavirus disease 2019 (COVID-19) pandemic has altered entire nations and their health systems. The greatest impact of the pandemic has been seen among vulnerable populations, such as those with comorbidities like heart diseases, kidney failure, obesity, or those with worse health determinants such as unemployment and poverty. In the current study, we are proposing previous exposure to fine-grained volcanic ashes as a risk factor for developing COVID-19. Based on several previous studies it has been known since the mid 1980s of the past century that volcanic ash is most likely an accelerating factor to suffer from different types of cancer, including lung or thyroid cancer. Our study postulates, that people who are most likely to be infected during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) widespread wave will be those with comorbidities that are related to previous exposure to volcanic ashes. We have explored 8703 satellite images from the past 21 y of available data from the National Oceanic and Atmospheric Administration (NOAA) database and correlated them with the data from the national institute of health statistics in Ecuador. Additionally, we provide more realistic numbers of fatalities due to the virus based on excess mortality data of 2020-2021, when compared with previous years. This study would be a very first of its kind combining social and spatial distribution of COVID-19 infections and volcanic ash distribution. The results and implications of our study will also help countries to identify such aforementioned vulnerable parts of the society, if the given geodynamic and volcanic settings are similar.
2021-05-19 2021 other research-article; Journal Article abstract-available 10.1017/dmp.2021.154 Volcanic Ash as a Precursor for SARS-CoV-2 Infection Among Susceptible Populations in Ecuador: A Satellite Imaging and Excess Mortality-Based Analysis. Toulkeridis T, Seqqat R, Torres Arias M, Salazar-Martinez R, Ortiz-Prado E, Chunga S, Vizuete K, Heredia-R M, Debut A. Disaster Med Public Health Prep. 2021;
SARS-CoV-2 Vaccines and the Skin.
Galván-Casas C, Català A, Muñoz-Santos C.
Actas Dermosifiliogr (Engl Ed). 2021; 112 (9)
DOI: 10.1016/j.adengl.2021.07.028
Vaccines against the severe acute respiratory coronavirus 2, which are the first to be used in humans against any coronavirus, were developed and produced in record time. Dermatologic adverse effects appeared during clinical trials and have also been described in the population since approval. Just as descriptions and categorization of skin manifestations of the coronavirus disease 2019 proved important for understanding the disease itself, characterizing the effects of vaccines may also further that goal. This paper reviews the properties of the different types of vaccines currently available and under development and describes how they interact with the immune system and the clinical signs they may cause. We focus on dermatologic adverse effects reported to date and recommendations for managing them.
2021-08-28 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.adengl.2021.07.028 SARS-CoV-2 Vaccines and the Skin. Galván-Casas C, Català A, Muñoz-Santos C. Actas Dermosifiliogr (Engl Ed). 2021; 112 (9)
Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study.
de Rojas I, Hernández I, Montrreal L, Quintela I, [...], Ruiz A.
J Pers Med. 2021; 11 (12)
DOI: 10.3390/jpm11121318
Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.
2021-12-07 2021 other research-article; Journal Article abstract-available 10.3390/jpm11121318 Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study. de Rojas I, Hernández I, Montrreal L, Quintela I, Calero M, Royo JL, Huerto Vilas R, González-Pérez A, Franco-Macías E, Macías J, Menéndez-González M, Frank-García A, Diez-Fairen M, Lage C, García-Madrona S, Aguilera N, García-González P, Puerta R, Sotolongo-Grau O, Alonso-Lana S, Rábano A, Arias Pastor A, Pastor AB, Corma-Gómez A, Martín Montes A, Martínez Rodríguez C, Buiza-Rueda D, Periñán MT, Rodriguez-Rodriguez E, Alvarez I, Rosas Allende I, Pineda JA, Bernal Sánchez-Arjona M, Fernández-Fuertes M, Mendoza S, Del Ser T, Gr Ace/Degesco Consortium, Garcia-Ribas G, Sánchez-Juan P, Pastor P, Bullido MJ, Álvarez V, Real LM, Mir P, Piñol-Ripoll G, García-Alberca JM, Medina M, Orellana A, Butler CR, Marquié M, Sáez ME, Carracedo Á, Tárraga L, Boada M, Ruiz A. J Pers Med. 2021; 11 (12)
Is the oral cavity relevant in SARS-CoV-2 pandemic?
Herrera D, Serrano J, Roldán S, Sanz M.
Clin Oral Investig. 2020; 24 (8)
DOI: 10.1007/s00784-020-03413-2

Objectives

Recent scientific evidences suggest a relevant role of the oral cavity in the transmission and pathogenicity of SARS-CoV-2.

Methods

A literature search was performed in PubMed, up to April 30, 2020, focusing on SARS-CoV-2, COVID-19, oral cavity, and antimicrobial agents.

Results

Oral viral load of SARS-CoV-2 has been associated with the severity of COVID-19, and thus, a reduction in the oral viral load could be associated with a decrease in the severity of the condition. Similarly, a decrease in the oral viral load would diminish the amount of virus expelled and reduce the risk of transmission, since (i) during the first 10 days, the virus mainly accumulates at the nasal, oral, and pharyngeal area; (ii) the number of angiotensin-converting enzyme (ACE2) receptor is greater in the salivary glands as compared with the lungs; and (iii) salivary droplets represent the most relevant transmission route. To reduce the oral viral load, antiseptic agents may be used, although the evidence on its efficacy is indirect and weak.

Conclusions

Antiseptic mouth rinses, such as those containing cetylpyridinium chloride or povidone-iodine, may be able to decrease the severity of COVID-19 by reducing oral viral load in infected subjects and decreasing the risk of transmission by limiting viral load in droplets, generated in normal life, or in aerosols, produced during dental procedures. Well-designed clinical and preclinical research must be conducted to support these hypotheses.

Clinical relevance

Antiseptic mouth rinses may help in decreasing the severity of COVID-19 and in reducing the risk of transmission.
2020-06-23 2020 other research-article; Journal Article abstract-available 10.1007/s00784-020-03413-2 Is the oral cavity relevant in SARS-CoV-2 pandemic? Herrera D, Serrano J, Roldán S, Sanz M. Clin Oral Investig. 2020; 24 (8)
Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic.
Di Natale C, La Manna S, De Benedictis I, Brandi P, [...], Marasco D.
Front Pharmacol. 2020; 11
DOI: 10.3389/fphar.2020.578382
At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.
2020-12-03 2020 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2020.578382 Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic. Di Natale C, La Manna S, De Benedictis I, Brandi P, Marasco D. Front Pharmacol. 2020; 11
An integrative look at SARS‑CoV‑2 (Review).
Ortega MA, Fraile-Martínez O, García-Montero C, García-Gallego S, [...], De la Torre B.
Int J Mol Med. 2021; 47 (2)
DOI: 10.3892/ijmm.2020.4828
SARS‑CoV‑2 is a newly discovered member of the betacoronaviruses and the etiological agent of the disease COVID‑19. SARS‑CoV‑2 is responsible for the worldwide pandemic which has been taking place in 2020, and is causing a markedly higher number of infections and deaths compared to previous coronaviruses, such as SARS‑CoV or MERS‑CoV. Based on updated scientific literature, the present review compiles the most relevant knowledge of SARS‑CoV‑2, COVID‑19 and the clinical and typical responses that patients have exhibited against this virus, discussing current and future therapies, and proposing strategies with which to combat the disease and prevent a further global threat. The aggressiveness of SARS‑CoV‑2 arises from its capacity to infect, and spread easily and rapidly through its tight interaction with the human angiotensin‑converting enzyme 2 (ACE‑2) receptor. While not all patients respond in a similar manner and may even be asymptomatic, a wide range of manifestations associated with COVID‑19 have been described, particularly in vulnerable population groups, such as the elderly or individuals with other underlying conditions. The proper function of the immune system plays a key role in an individual's favorable response to SARS‑CoV‑2 infection. A hyperactivated response, on the contrary, could account for the more severe cases of COVID‑19, and this may finally lead to respiratory insufficiency and other complications, such as thrombotic or thromboembolic events. The development of novel therapies and vaccines designed to control and regulate a proper immune system response will be key to clinical management, prevention measures and effective population screening to attenuate the transmission of this novel RNA virus.
2020-12-22 2020 other research-article; Review; Journal Article abstract-available 10.3892/ijmm.2020.4828 An integrative look at SARS‑CoV‑2 (Review). Ortega MA, Fraile-Martínez O, García-Montero C, García-Gallego S, Sánchez-Trujillo L, Torres-Carranza D, Álvarez-Mon MÁ, Pekarek L, García-Honduvilla N, Bujan J, Álvarez-Mon M, Asúnsolo Á, De la Torre B. Int J Mol Med. 2021; 47 (2)
The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019.
Coto E, Avanzas P, Gómez J.
Eur Cardiol. 2021; 16
DOI: 10.15420/ecr.2020.30
The renin-aldosterone-angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host's expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity.
2021-02-01 2021 other review-article; Review; Journal Article abstract-available 10.15420/ecr.2020.30 The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019. Coto E, Avanzas P, Gómez J. Eur Cardiol. 2021; 16
Rapid and Efficient Detection of the SARS-CoV-2 Spike Protein Using an Electrochemical Aptamer-Based Sensor.
Idili A, Parolo C, Alvarez-Diduk R, Merkoçi A.
ACS Sens. 2021; 6 (8)
DOI: 10.1021/acssensors.1c01222
The availability of sensors able to rapidly detect SARS-CoV-2 directly in biological fluids in a single step would allow performing massive diagnostic testing to track in real time and contain the spread of COVID-19. Motivated by this, here, we developed an electrochemical aptamer-based (EAB) sensor able to achieve the rapid, reagentless, and quantitative measurement of the SARS-CoV-2 spike (S) protein. First, we demonstrated the ability of the selected aptamer to undergo a binding-induced conformational change in the presence of its target using fluorescence spectroscopy. Then, we engineered the aptamer to work as a bioreceptor in the EAB platform and we demonstrated its sensitivity and specificity. Finally, to demonstrate the clinical potential of the sensor, we tested it directly in biological fluids (serum and artificial saliva), achieving the rapid (minutes) and single-step detection of the S protein in its clinical range.
2021-08-10 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1021/acssensors.1c01222 Rapid and Efficient Detection of the SARS-CoV-2 Spike Protein Using an Electrochemical Aptamer-Based Sensor. Idili A, Parolo C, Alvarez-Diduk R, Merkoçi A. ACS Sens. 2021; 6 (8)
In-vivo evidence of systemic endothelial vascular dysfunction in COVID-19.
Mejia-Renteria H, Travieso A, Sagir A, Martínez-Gómez E, [...], Escaned J.
Int J Cardiol. 2021; 345
DOI: 10.1016/j.ijcard.2021.10.140

Background

Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID-19. We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID-19 patients from a non-invasive approach with reactive hyperemia peripheral arterial tonometry (PAT).

Methods

This is a prospective, observational, case-control and blinded study. The population was comprised by 3 groups: patients investigated during acute COVID-19 (group 1), patients investigated during past COVID-19 (group 2), and controls 1:1 matched to COVID-19 patients by demographics and cardiovascular risk factors (group 3). The natural logarithmic scaled reactive hyperemia index (LnRHI), a measure of endothelium-mediated dilation of peripheral arteries, was obtained in all the participants and compared between study groups.

Results

144 participants were enrolled (72 COVID-19 patients and 72 matched controls). Median time from COVID-19 symptoms to PAT assessment was 9.5 and 101.5 days in groups 1 and 2, respectively. LnRHI was significantly lower in group 2 compared to both group 1 and controls (0.53 ± 0.23 group 2 vs. 0.72 ± 0.26 group 1, p = 0.0043; and 0.79 ± 0.23 in group 3, p < 0.0001). In addition, within group 1, it was observed a markedly decrease in LnRHI from acute COVID-19 to post infection stage (0.73 ± 0.23 vs. 0.42 ± 0.26, p = 0.0042).

Conclusions

This study suggests a deleterious effect of SARS-CoV-2 infection on systemic vascular endothelial function. These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID-19 patients and post-COVID syndrome using non-invasive techniques.
2021-10-24 2021 other brief-report; Journal Article; Observational Study abstract-available 10.1016/j.ijcard.2021.10.140 In-vivo evidence of systemic endothelial vascular dysfunction in COVID-19. Mejia-Renteria H, Travieso A, Sagir A, Martínez-Gómez E, Carrascosa-Granada A, Toya T, Núñez-Gil IJ, Estrada V, Lerman A, Escaned J. Int J Cardiol. 2021; 345
Clinical Presentation of the SARS-CoV-2 Virus Infection and Predictive Validity of the PCR Test in Primary Health Care Worker Patients of the Spanish National Health System.
Romero-Rodríguez E, Pérula-de Torres LA, González-Lama J, Jiménez-García C, [...], González-Santos J.
J Clin Med. 2022; 11 (1)
DOI: 10.3390/jcm11010243

Background

Despite the impact that the SARS-CoV-2 virus infection has presented in Spain, data on the diagnostic capacity of the symptoms associated with this infection are limited, especially among patients with mild symptoms and who are detected in the primary care field (PC). The objective of the present study was to know the associated symptoms and their predictive criterial validity in SARS-CoV-2 infection among professionals working in PC.

Methods

A cross-sectional, multicenter study was carried out in the Spanish National Health System, through an epidemiological survey directed to patients who underwent the PCR test for SARS-CoV-2 in the PC setting.

Results

A total of 1612 patients participated, of which 86.6% were PC healthcare professionals, and of these, 67.4% family doctors. Hyposmia, with a sensitivity of 42.69% (95% CI: 37.30-48.08) and a specificity of 95.91% (95% CI: 94.78-97.03), and ageusia with a sensitivity of 39.47% (34.15-44.80) and a specificity of 95.20% (93.98-96.41) were the symptoms with the highest criteria validity indexes.

Conclusions

This study identifies the specific symptoms of loss of smell or taste as the most frequently associated with SARS-CoV-2 infection, essential in the detection of COVID-19 given its high frequency and predictive capacity.
2022-01-04 2022 other research-article; Journal Article abstract-available 10.3390/jcm11010243 Clinical Presentation of the SARS-CoV-2 Virus Infection and Predictive Validity of the PCR Test in Primary Health Care Worker Patients of the Spanish National Health System. Romero-Rodríguez E, Pérula-de Torres LA, González-Lama J, Jiménez-García C, Castro-Jiménez RA, González-Bernal JJ, Rodríguez-Fernández P, Mielgo-Ayuso J, Santamaría-Peláez M, González-Santos J. J Clin Med. 2022; 11 (1)
Alpha variant SARS-CoV-2 infection: How it all starts.
Domingo P, de Benito N.
EBioMedicine. 2021; 74
DOI: 10.1016/j.ebiom.2021.103703
2021-11-17 2021 other discussion; Journal Article 10.1016/j.ebiom.2021.103703 Alpha variant SARS-CoV-2 infection: How it all starts. Domingo P, de Benito N. EBioMedicine. 2021; 74
JAK-STAT Pathway: A Novel Target to Tackle Viral Infections.
Ezeonwumelu IJ, Garcia-Vidal E, Ballana E.
Viruses. 2021; 13 (12)
DOI: 10.3390/v13122379
Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections.
2021-11-27 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/v13122379 JAK-STAT Pathway: A Novel Target to Tackle Viral Infections. Ezeonwumelu IJ, Garcia-Vidal E, Ballana E. Viruses. 2021; 13 (12)
MOV10 Helicase Interacts with Coronavirus Nucleocapsid Protein and Has Antiviral Activity.
Wang L, Sola I, Enjuanes L, Zuñiga S.
mBio. 2021; 12 (5)
DOI: 10.1128/mbio.01316-21
Coronaviruses (CoVs) are emergent pathogens that may cause life-threatening respiratory diseases in humans. Understanding of CoV-host interactions may help to identify novel therapeutic targets. MOV10 is an RNA helicase involved in different steps of cellular RNA metabolism. Both MOV10 antiviral and proviral activities have been described in a limited number of viruses, but this protein has not been previously associated with CoVs. We found that during Middle East respiratory syndrome coronavirus (MERS-CoV) infection, MOV10 aggregated in cytoplasmic structures colocalizing with viral nucleocapsid (N) protein. MOV10-N interaction was confirmed by endogenous MOV10 coimmunoprecipitation, and the presence of other cellular proteins was also detected in MOV10 complexes. MOV10 silencing significantly increased both N protein accumulation and virus titer, with no changes in the accumulation of viral RNAs. Moreover, MOV10 overexpression caused a 10-fold decrease in viral titers. These data indicated that MOV10 has antiviral activity during MERS-CoV infection. We postulated that this activity could be mediated by viral RNA sequestration, and in fact, RNA immunoprecipitation data showed the presence of viral RNAs in the MOV10 cytoplasmic complexes. Expression of wild-type MOV10 or of a MOV10 mutant without helicase activity in MOV10 knockout cell lines, developed by CRISPR-Cas technology, indicated that the helicase activity of MOV10 was required for its antiviral effect. Interestingly MOV10-N interaction was conserved in other mildly or highly pathogenic human CoVs, including the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although MOV10 antiviral activity was found only in highly pathogenic CoVs, suggesting a potential role of MOV10 in the modulation of human CoVs pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging pathogens causing life-threatening diseases in humans. Knowledge of virus-host interactions and viral subversion mechanisms of host pathways is required for the development of effective countermeasures against CoVs. The interaction between cellular RNA helicase MOV10 and nucleocapsid (N) protein from several human CoVs is shown. Using MERS-CoV as a model, we demonstrate that MOV10 has antiviral function, requiring its helicase activity, most likely mediated by viral RNA sequestration in cytoplasmic ribonucleoprotein structures. Furthermore, we found that MOV10 antiviral activity may act only in highly pathogenic human CoVs, suggesting a role for MOV10 in modulating CoVs pathogenesis. The present study uncovers a complex network of viral and cellular RNAs and proteins interaction modulating the antiviral response against CoVs.
2021-09-14 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/mbio.01316-21 MOV10 Helicase Interacts with Coronavirus Nucleocapsid Protein and Has Antiviral Activity. Wang L, Sola I, Enjuanes L, Zuñiga S. mBio. 2021; 12 (5)
Is asthma associated with COVID-19 infection? A UK Biobank analysis.
Lodge CJ, Doherty A, Bui DS, Cassim R, [...], Dharmage SC.
ERJ Open Res. 2021; 7 (4)
DOI: 10.1183/23120541.00309-2021

Background

The relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma.

Methods

We used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV1) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index.

Results

There was a reduced risk of a positive test associated with early-onset asthma (<13 years) (OR 0.91, 95% CI 0.84-0.99). This was found for participants with early-onset asthma who were male (OR 0.87, 95% CI 0.78-0.98), nonsmokers (OR 0.87, 95% CI 0.78-0.98), overweight/obese (OR 0.85, 95% CI 0.77-0.93) and non-Black (OR 0.90, 95% CI 0.82-0.98). There was increased risk amongst early-onset individuals with asthma in the highest compared to lowest quartile of lung function (1.44, 1.05-1.72).

Conclusion

Amongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.
2021-10-01 2021 other research-article; Journal Article abstract-available 10.1183/23120541.00309-2021 Is asthma associated with COVID-19 infection? A UK Biobank analysis. Lodge CJ, Doherty A, Bui DS, Cassim R, Lowe AJ, Agusti A, Russell MA, Dharmage SC. ERJ Open Res. 2021; 7 (4)
Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study.
de Miguel-Gómez L, Romeu M, Castells-Ballester J, Pellicer N, [...], Cervelló I.
Am J Obstet Gynecol. 2021;
DOI: 10.1016/j.ajog.2021.10.019
2021-10-21 2021 other Letter 10.1016/j.ajog.2021.10.019 Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study. de Miguel-Gómez L, Romeu M, Castells-Ballester J, Pellicer N, Faus A, Mullor JL, Pellicer A, Cervelló I. Am J Obstet Gynecol. 2021;
SARS-CoV-2, COVID-19, skin and immunology - What do we know so far?
Novak N, Peng W, Naegeli MC, Galvan C, [...], Catala A.
Allergy. 2021; 76 (3)
DOI: 10.1111/all.14498
The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.
2020-08-12 2020 other Research Support, Non-U.S. Gov't; research-article; Review; Journal Article abstract-available 10.1111/all.14498 SARS-CoV-2, COVID-19, skin and immunology - What do we know so far? Novak N, Peng W, Naegeli MC, Galvan C, Kolm-Djamei I, Brüggen C, Cabanillas B, Schmid-Grendelmeier P, Catala A. Allergy. 2021; 76 (3)
Utility of a commercial RT-qPCR assay to detect SARS-CoV-2 gene variations as an indicator of lineages.
Trobajo-Sanmartín C, Miqueleiz A, Portillo ME, Fernández-Huerta M, [...], Ezpeleta C.
J Virol Methods. 2022; 300
DOI: 10.1016/j.jviromet.2021.114428

Background

The World Health Organization (WHO) recommended RT-qPCR tests as the reference technique for SARS-CoV-2 molecular detection, however with the rapid spread of the infection, mutations in specific RT-qPCR target regions have been widely described could allow the presumptive identification.

Objective

In this study, we evaluated the analytical performance of the Allplex™SARS-CoV-2/FluA/FluB/RSV assay for the additional presumptive identification of SARS-CoV-2 variants in a real-life setting.

Results

We observed gene-specific changes in the cycle threshold (Ct) of the N and RdRp genes compared with the Ct yielded for the S gene when the SARS-CoV-2 testing was performed Allplex™SARS-CoV-2/FluA/FluB/RSV assay. Seventeen samples showed Ct variations in the N and/or RdRp. In 10 cases, the N gene was affected, delayed or negative and in 14 cases, the RdRp gene showed a delay or negative concerning the S gene. A delay in the Ct of both genes (RdRp and N) was observed in six cases. Sequencing determined that all samples identified as B.1.1.7 showed changes in the PCR curves of the N and RdRp. However, samples identified as B.1.177 only showed variations for the RdRp gene.

Conclusions

Allplex™SARS-CoV-2/FluA/FluB/RSV assay, the diagnosis could presumably allow the rapid assignment of lineages B.1.1.7 and B.1.177, and emphasizes the importance of exhaustive surveillance for circulating variants of the SARS-CoV-2 virus to reduce community transmission.
2021-12-11 2021 fondo-covid brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1016/j.jviromet.2021.114428 Utility of a commercial RT-qPCR assay to detect SARS-CoV-2 gene variations as an indicator of lineages. Trobajo-Sanmartín C, Miqueleiz A, Portillo ME, Fernández-Huerta M, Navascués A, Castilla J, Ezpeleta C. J Virol Methods. 2022; 300
Clinical features and radiological manifestations of COVID-19 disease.
Landete P, Quezada Loaiza CA, Aldave-Orzaiz B, Muñiz SH, [...], Couñago F.
World J Radiol. 2020; 12 (11)
DOI: 10.4329/wjr.v12.i11.247
Coronavirus disease 2019 (COVID-19) was discovered after unusual cases of severe pneumonia emerged in December 2019 in Wuhan Province (China). Coronavirus is a family of single-stranded RNA viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person to person. Although asymptomatic individuals can transmit the virus, symptomatic patients are more contagious. The incubation period ranges from 3-7 d and symptoms are mainly respiratory, including pneumonia or pulmonary embolism in severe cases. Elevated serum levels of interleukins (IL)-2, IL-6, IL-7 indicate the presence of cytokine release syndrome, which is associated with disease severity. The disease has three main phases: Viral infection, pulmonary involvement, and hyperinflammation. To date, no treatment has proved to be safe or effective. Chest X-ray and computed tomography (CT) are the primary imaging tests for diagnosis of SARS-CoV-2 pneumonia, follow-up, and detection of complications. The main radiological findings are ground-glass opacification and areas of consolidation. The long-term clinical course is unknown, although some patients may develop pulmonary fibrosis. Positron emission tomography-computed tomography (PET-CT) is useful to assess pulmonary involvement, to define the affected areas, and to assess treatment response. The pathophysiology and clinical course of COVID-19 infection remain poorly understood. However, patterns detected on CT and PET-CT may help to diagnose and guide treatment. In this mini review, we analyze the clinical manifestations and radiological findings of COVID-19 infection.
2020-11-01 2020 other review-article; Review; Journal Article abstract-available 10.4329/wjr.v12.i11.247 Clinical features and radiological manifestations of COVID-19 disease. Landete P, Quezada Loaiza CA, Aldave-Orzaiz B, Muñiz SH, Maldonado A, Zamora E, Sam Cerna AC, Del Cerro E, Alonso RC, Couñago F. World J Radiol. 2020; 12 (11)
Structural analysis of SARS-CoV-2 genome and predictions of the human interactome.
Vandelli A, Monti M, Milanetti E, Armaos A, [...], Tartaglia GG.
Nucleic Acids Res. 2020; 48 (20)
DOI: 10.1093/nar/gkaa864
Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2000 coronaviruses and computed >100 000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic regions display different degrees of conservation. SARS-CoV-2 domain encompassing nucleotides 22 500-23 000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S is connected to different levels of viral entry in human cells within the population. Our predictions indicate that the 5' end of SARS-CoV-2 is highly structured and interacts with several human proteins. The binding proteins are involved in viral RNA processing, include double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated assemblies. We propose that these proteins, also implicated in viral infections such as HIV, are selectively recruited by SARS-CoV-2 genome to alter transcriptional and post-transcriptional regulation of host cells and to promote viral replication.
2020-11-01 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/nar/gkaa864 Structural analysis of SARS-CoV-2 genome and predictions of the human interactome. Vandelli A, Monti M, Milanetti E, Armaos A, Rupert J, Zacco E, Bechara E, Delli Ponti R, Tartaglia GG. Nucleic Acids Res. 2020; 48 (20)
Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.
Chauvin M, Larsen M, Quirant B, Quentric P, [...], Sauce D.
Front Cell Infect Microbiol. 2021; 11
DOI: 10.3389/fcimb.2021.709893

Highlights

Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome.

Background

Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.

Methods

We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.

Results

Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.

Conclusion

We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
2021-08-23 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.3389/fcimb.2021.709893 Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients. Chauvin M, Larsen M, Quirant B, Quentric P, Dorgham K, Royer L, Vallet H, Guihot A, Combadière B, Combadière C, Barallat J, Mayaux J, Luyt CE, Mathian A, Amoura Z, Boddaert J, Armestar F, Gorochov G, Martinez-Caceres E, Sauce D. Front Cell Infect Microbiol. 2021; 11
Persistent headache after COVID-19: Pathophysioloy, clinic and treatment Cefalea persistente tras el COVID-19: Fisiopatología, clínica y tratamiento
Membrilla J, Caronna E, Trigo-López J, González-Martínez A, [...], Díaz de Terán J.
Neurology Perspectives. 2021; 1
DOI:
SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors’ clinical experience.
2021-12-01 2021 other review-article; Review; Journal Article abstract-available Persistent headache after COVID-19: Pathophysioloy, clinic and treatment Cefalea persistente tras el COVID-19: Fisiopatología, clínica y tratamiento Membrilla J, Caronna E, Trigo-López J, González-Martínez A, Layos-Romero A, Pozo-Rosich P, Guerrero-Peral Á, Gago-Veiga A, Andrés-López A, Díaz de Terán J. Neurology Perspectives. 2021; 1
Evaluation of two RT-PCR techniques for SARS-CoV-2 RNA detection in serum for microbiological diagnosis.
Martín Ramírez A, Zurita Cruz ND, Gutiérrez-Cobos A, Rodríguez Serrano DA, [...], Cardeñoso Domingo L.
J Virol Methods. 2022; 300
DOI: 10.1016/j.jviromet.2021.114411
Presence of SARS-CoV-2 RNA in serum (viremia) of COVID-19 patients has been related to poor prognosis and death. The aim of this study was to evaluate both the ability to detect viremia in COVID-19 patients of two commercial reverse real-time-PCR (rRT-PCR) tests, Cobas® and TaqPath™, comparing them with a gold standard method, and their implementation in microbiology laboratories. This retrospective cohort study included 303 adult patients (203 diagnosed with COVID-19 and 100 non-COVID-19 patients) admitted to a tertiary hospital, with at least one serum sample collected within the first 48 h from admission. A total of 365 serum samples were included: 100 from non-COVID patients (pre-pandemic and pandemic control groups) and 265 from COVID-19 patients. Serum samples were considered positive when at least one target was detected. All patients in control groups showed negative viremia. Cobas® and TaqPath™ tests showed specificity and Positive Predictive Value over 96%. Nevertheless, sensitivity (53.72 and 73.63, respectively) and Negative Predictive Value (64.78 and 75) were lower. Viremia difference between ICU and non-ICU patients was significant (p ≤ 0.001) for both techniques. Consequently, SARS-CoV-2 viremia detection by both rRT-PCR tests should be considered a good tool to stratify COVID-19 patients and could be implemented in microbiology laboratories.
2021-12-12 2021 other research-article; Journal Article abstract-available 10.1016/j.jviromet.2021.114411 Evaluation of two RT-PCR techniques for SARS-CoV-2 RNA detection in serum for microbiological diagnosis. Martín Ramírez A, Zurita Cruz ND, Gutiérrez-Cobos A, Rodríguez Serrano DA, González Álvaro I, Roy Vallejo E, Gómez de Frutos S, Fontán García-Rodrigo L, Cardeñoso Domingo L. J Virol Methods. 2022; 300
Chest CT abnormalities in COVID-19: a systematic review.
Ghayda RA, Lee KH, Kim JS, Lee S, [...], Shin JI.
Int J Med Sci. 2021; 18 (15)
DOI: 10.7150/ijms.50568
Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.
2021-08-01 2021 other research-article; Systematic Review; Journal Article abstract-available 10.7150/ijms.50568 Chest CT abnormalities in COVID-19: a systematic review. Ghayda RA, Lee KH, Kim JS, Lee S, Hong SH, Kim KS, Kim KE, Seok J, Kim H, Seo J, Lee S, Koyanagi A, Jacob L, Smith L, Li H, Kronbichler A, Shin JI. Int J Med Sci. 2021; 18 (15)
Immune response in SARS-CoV-2.
Aguilar-Shea AL, Mayo CG.
J Family Med Prim Care. 2020; 9 (9)
DOI: 10.4103/jfmpc.jfmpc_1539_20
2020-09-30 2020 other letter; Journal Article 10.4103/jfmpc.jfmpc_1539_20 Immune response in SARS-CoV-2. Aguilar-Shea AL, Mayo CG. J Family Med Prim Care. 2020; 9 (9)
COVID-19 and human reproduction: A pandemic that packs a serious punch.
Anifandis G, Tempest HG, Oliva R, Swanson GM, [...], Krawetz SA.
Syst Biol Reprod Med. 2021; 67 (1)
DOI: 10.1080/19396368.2020.1855271
The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.
2021-02-01 2021 other Review; Journal Article abstract-available 10.1080/19396368.2020.1855271 COVID-19 and human reproduction: A pandemic that packs a serious punch. Anifandis G, Tempest HG, Oliva R, Swanson GM, Simopoulou M, Easley CA, Primig M, Messini CI, Turek PJ, Sutovsky P, Ory SJ, Krawetz SA. Syst Biol Reprod Med. 2021; 67 (1)
Scientific effort in combating COVID-19 in obstetrics and gynecology.
Martinez-Portilla RJ, Gil MM, Poon LC.
Ultrasound Obstet Gynecol. 2021; 57 (2)
DOI: 10.1002/uog.23584
2021-02-01 2021 other article-commentary; Comment; Journal Article 10.1002/uog.23584 Scientific effort in combating COVID-19 in obstetrics and gynecology. Martinez-Portilla RJ, Gil MM, Poon LC. Ultrasound Obstet Gynecol. 2021; 57 (2)
First Detection of SARS-CoV-2 B.1.1.7 Variant of Concern in an Asymptomatic Dog in Spain.
Barroso-Arévalo S, Rivera B, Domínguez L, Sánchez-Vizcaíno JM.
Viruses. 2021; 13 (7)
DOI: 10.3390/v13071379
Natural SARS-CoV-2 infection in pets has been widely documented during the last year. Although the majority of reports suggested that dogs' susceptibility to the infection is low, little is known about viral pathogenicity and transmissibility in the case of variants of concern, such as B.1.1.7 in this species. Here, as part of a large-scale study on SARS-CoV-2 prevalence in pets in Spain, we have detected the B.1.1.7 variant of concern (VOC) in a dog whose owners were infected with SARS-CoV-2. The animal did not present any symptoms, but viral loads were high in the nasal and rectal swabs. In addition, viral isolation was possible from both swabs, demonstrating that the dog was shedding infectious virus. Seroconversion occurred 23 days after the first sampling. This study documents the first detection of B.1.1.7 VOC in a dog in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.
2021-07-15 2021 fondo-covid Research Support, Non-U.S. Gov't; Case Reports; case-report abstract-available 10.3390/v13071379 First Detection of SARS-CoV-2 B.1.1.7 Variant of Concern in an Asymptomatic Dog in Spain. Barroso-Arévalo S, Rivera B, Domínguez L, Sánchez-Vizcaíno JM. Viruses. 2021; 13 (7)
Severe Acute Respiratory Syndrome Coronavirus 2 Normalized Viral Loads and Subgenomic RNA Detection as Tools for Improving Clinical Decision Making and Work Reincorporation.
Santos Bravo M, Nicolás D, Berengua C, Fernandez M, [...], Marcos MA.
J Infect Dis. 2021; 224 (8)
DOI: 10.1093/infdis/jiab394

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) provides a highly variable cycle threshold (Ct) value that cannot distinguish viral infectivity. Subgenomic ribonucleic acid (sgRNA) has been used to monitor active replication. Given the importance of long RT-PCR positivity and the need for work reincorporation and discontinuing isolation, we studied the functionality of normalized viral loads (NVLs) for patient monitoring and sgRNA for viral infectivity detection.

Methods

The NVLs measured through the Nucleocapsid and RNA-dependent-RNA-polymerase genes and sgRNA RT-PCRs were performed in 2 consecutive swabs from 84 healthcare workers.

Results

The NVLs provided similar and accurate quantities of both genes of SARS-CoV-2 at 2 different timepoints of infection, overcoming Ct-value and swab collection variability. Among SARS-CoV-2-positive samples, 51.19% were sgRNA-positive in the 1st RT-PCR and 5.95% in the 2nd RT-PCR. All sgRNA-positive samples had >4 log10 RNA copies/1000 cells, whereas samples with ≤1 log10 NVLs were sgRNA-negative. Although NVLs were positive until 29 days after symptom onset, 84.1% of sgRNA-positive samples were from the first 7 days, which correlated with viral culture viability. Multivariate analyses showed that sgRNA, NVLs, and days of symptoms were significantly associated (P < .001).

Conclusions

The NVLs and sgRNA are 2 rapid accessible techniques that could be easily implemented in routine hospital practice providing a useful proxy for viral infectivity and coronavirus disease 2019 patient follow-up.
2021-10-01 2021 other research-article; Journal Article; Observational Study abstract-available 10.1093/infdis/jiab394 Severe Acute Respiratory Syndrome Coronavirus 2 Normalized Viral Loads and Subgenomic RNA Detection as Tools for Improving Clinical Decision Making and Work Reincorporation. Santos Bravo M, Nicolás D, Berengua C, Fernandez M, Hurtado JC, Tortajada M, Barroso S, Vilella A, Mosquera MM, Vila J, Marcos MA. J Infect Dis. 2021; 224 (8)
Undetectable viral RNA in oocytes from SARS-CoV-2 positive women.
Barragan M, Guillén JJ, Martin-Palomino N, Rodriguez A, [...], Vassena R.
Hum Reprod. 2021; 36 (2)
DOI: 10.1093/humrep/deaa284
A central concern for the safe provision of ART during the current coronavirus disease 2019 (COVID-19) pandemic is the possibility of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through gametes and preimplantation embryos. Unfortunately, data on SARS-CoV-2 viral presence in oocytes of infected individuals are not available to date. We describe the case of two women who underwent controlled ovarian stimulation and tested positive to SARS-CoV-2 infection by PCR on the day of oocyte collection. The viral RNA for gene N was undetectable in all the oocytes analyzed from the two women.
2021-01-01 2021 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report abstract-available 10.1093/humrep/deaa284 Undetectable viral RNA in oocytes from SARS-CoV-2 positive women. Barragan M, Guillén JJ, Martin-Palomino N, Rodriguez A, Vassena R. Hum Reprod. 2021; 36 (2)
COVID-19, A new challenge in the dental practice.
Silvestre FJ, Martinez-Herrera M, Márquez-Arrico CF, Silvestre-Rangil J.
J Clin Exp Dent. 2021; 13 (7)
DOI: 10.4317/jced.57362

Background

This review was conducted in order to learn the latest information about how to prevent cross-infection of COVID-19 in dentistry. The aim of this study is offer a clinical protocol to reduce the risk of infection of COVID-19 in dental settings.

Material and methods

We carried out a review based on the PRISMA guide (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the following three databases: PubMed, Embase and Scopus. The search strategy was performed in the three databases applying the search terms "COVID-19 AND dental", "COVID-19 AND dentistry", selecting human studies published from November 2019 to May 2020. English publications regarding COVID-19 as the central topic of the research were eligible for inclusion, regardless of study design. There are very few published studies on the association between COVID-19 and dentistry, for that reason we also included the English abstract of two studies written in Chinese. The following exclusion criteria were established: animal studies and in vitro studies.

Results

The search identified a total of 212 articles, of which 54 were preselected, and 23 were finally included in the review on the basis of the inclusion and exclusion criteria. We collected all the information about routes of general and oral infection, dental patient evaluation and cross-infection control in Dental Clinic in the selected studies.

Conclusions

Cross infection in the dental clinic involve a very important risk due to the return to dental settings after periods of social isolation of the population after the epidemic outbreak of SARS-CoV-2. Therefore, we must take adequate and sufficient security measures to protect the patients and the dental clinic staff. Key words:COVID-19, COVID-19 cross infection risk, COVID-19 prevention in Dentistry, COVID-19 in Dental Clinic.
2021-07-01 2021 other review-article; Review; Journal Article abstract-available 10.4317/jced.57362 COVID-19, A new challenge in the dental practice. Silvestre FJ, Martinez-Herrera M, Márquez-Arrico CF, Silvestre-Rangil J. J Clin Exp Dent. 2021; 13 (7)
[Scoping review of coronavirus case series (SARS-CoV, MERS-CoV and SARS-CoV-2) and their obstetric and neonatal results].
Rodríguez-Blanco N, Vegara-Lopez I, Aleo-Giner L, Tuells J.
Rev Esp Quimioter. 2020; 33 (5)
DOI: 10.37201/req/064.2020

Objective

The appearance of new infectious diseases, such as COVID-19, poses a challenge in monitoring pregnancy and preventing obstetric and neonatal complications. A scoping review has the objective to review the information available in pregnant women infected with the MERS-CoV, SARSCoV, SARS-CoV-2 coronaviruses to assess the similarities in terms of and differences in the clinical characteristics of the mothers and neonatal outcomes.

Methods

We carried out a bibliographic search (scoping review) according to the PRISMA guidelines between March and April 2020 in the MEDLINE, SciELO, and CUIDEN databases and the Elsevier COVID-19 Information Center.

Results

We analyzed 20 articles with a total of 102 cases. 9 of MERS-CoV, 14 of SARS-CoV and 79 of SARS-CoV-2. Fever (75.5%) and pneumonia (73.5%) were the most frequent symptoms in infected pregnant women. The most frequent obstetric complications were the threat of premature delivery (23.5%) and caesarean section (74.5%). No vertical transmission was documented in any of the infants.

Conclusions

All three coronaviruses produce pneumonia with very similar symptoms, being milder in the case of SARSCoV2. Despite documented obstetric complications, neonatal outcomes are mostly favorable. Increased knowledge is needed to improve and prevent obstetric and neonatal complications from these infections in pregnant women.
2020-07-20 2020 other research-article; Systematic Review abstract-available 10.37201/req/064.2020 [Scoping review of coronavirus case series (SARS-CoV, MERS-CoV and SARS-CoV-2) and their obstetric and neonatal results]. Rodríguez-Blanco N, Vegara-Lopez I, Aleo-Giner L, Tuells J. Rev Esp Quimioter. 2020; 33 (5)
Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.
Tamayo-Velasco Á, Peñarrubia Ponce MJ, Álvarez FJ, Gonzalo-Benito H, [...], Martínez-Paz P.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.726283
Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.
2021-10-13 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2021.726283 Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can. Tamayo-Velasco Á, Peñarrubia Ponce MJ, Álvarez FJ, Gonzalo-Benito H, de la Fuente I, Pérez-González S, Rico L, Jiménez García MT, Sánchez Rodríguez A, Hijas Villaizan M, Martín-Fernández M, Dueñas C, Gómez-Sánchez E, Heredia-Rodríguez M, Gorgojo-Galindo Ó, Fernández I, Del Río L, Carnicero-Frutos I, Muñoz-Moreno MF, Tamayo E, Bernardo D, Martínez-Paz P. Front Immunol. 2021; 12
Longitudinal study of a SARS-CoV-2 infection in an immunocompromised patient with X-linked agammaglobulinemia.
Ciuffreda L, Lorenzo-Salazar JM, Alcoba-Florez J, Rodriguez-Pérez H, [...], Flores C.
J Infect. 2021; 83 (5)
DOI: 10.1016/j.jinf.2021.07.028
2021-07-28 2021 other Letter; Comment 10.1016/j.jinf.2021.07.028 Longitudinal study of a SARS-CoV-2 infection in an immunocompromised patient with X-linked agammaglobulinemia. Ciuffreda L, Lorenzo-Salazar JM, Alcoba-Florez J, Rodriguez-Pérez H, Gil-Campesino H, Íñigo-Campos A, García-Martínez de Artola D, Valenzuela-Fernández A, Hayek-Peraza M, Rojo-Alba S, Alvarez-Argüelles ME, Díez-Gil O, González-Montelongo R, Flores C. J Infect. 2021; 83 (5)
Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogenicity studies.
Vergara-Alert J, Rodon J, Carrillo J, Te N, [...], Segalés J.
Transbound Emerg Dis. 2021; 68 (4)
DOI: 10.1111/tbed.13861
Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through different routes, including intranasal, intratracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS-CoV-2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).
2020-10-23 2020 other brief-report; Journal Article abstract-available 10.1111/tbed.13861 Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogenicity studies. Vergara-Alert J, Rodon J, Carrillo J, Te N, Izquierdo-Useros N, Rodríguez de la Concepción ML, Ávila-Nieto C, Guallar V, Valencia A, Cantero G, Blanco J, Clotet B, Bensaid A, Segalés J. Transbound Emerg Dis. 2021; 68 (4)
Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses.
Li J, Boix E.
Virulence. 2021; 12 (1)
DOI: 10.1080/21505594.2021.1871823
Owing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1080/21505594.2021.1871823 Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses. Li J, Boix E. Virulence. 2021; 12 (1)
COVID-19: Relationship and Impact on Breastfeeding-A Systematic Review.
Pérez-Bermejo M, Peris-Ochando B, Murillo-Llorente MT.
Nutrients. 2021; 13 (9)
DOI: 10.3390/nu13092972
COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that was declared a Public Health Emergency of International Concern by the World Health Organization (WHO). One major problem faced is whether breastfeeding by mothers infected with the virus is safe. The objective of this work is to study the impact that the SARS-CoV-2 virus can have on breastfeeding, and whether the virus or antibodies can be transmitted from mother to child through milk. We carried out a systematic review of studies focusing on the impact of SARS-CoV-2 on breastfeeding by mothers infected with the virus. The bibliographic search was done through Medline (Pubmed), MedlinePlus and Google Scholar. From 292 records, the title and summary of each were examined according to the criteria, and whether they meet the selection criteria was also analysed. A total of 30 articles are included, of which 26 deal with the study of RNA virus in breastmilk and its involvement in breastfeeding and four on the study of SARS-CoV-2 antibodies in milk. Most studies have been conducted in China. Breastfeeding by mothers infected with SARS-CoV-2 is highly recommended for infants, if the health of the mother and the infant allow for it. Direct breastfeeding and maintaining appropriate protective measures should be encouraged. Should the mother's health condition not permit direct breastfeeding, infants should be fed with pumped breastmilk or donor milk.
2021-08-26 2021 other Systematic Review; review-article; Journal Article abstract-available 10.3390/nu13092972 COVID-19: Relationship and Impact on Breastfeeding-A Systematic Review. Pérez-Bermejo M, Peris-Ochando B, Murillo-Llorente MT. Nutrients. 2021; 13 (9)
The Relevance of Monoclonal Antibodies in the Treatment of COVID-19.
Torrente-López A, Hermosilla J, Navas N, Cuadros-Rodríguez L, [...], Salmerón-García A.
Vaccines (Basel). 2021; 9 (6)
DOI: 10.3390/vaccines9060557
Major efforts have been made in the search for effective treatments since the outbreak of the COVID-19 infection in December 2019. Extensive research has been conducted on drugs that are already available and new treatments are also under development. Within this context, therapeutic monoclonal antibodies (mAbs) have been the subject of widespread investigation focusing on two target-based groups, i.e., non-SARS-CoV-2 specific mAbs, that target immune system responses, and SARS-CoV-2 specific mAbs, designed to neutralize the virus protein structure. Here we review the latest literature about the use of mAbs in order to describe the state of the art of the clinical trials and the benefits of using these biotherapeutics in the treatment of COVID-19. The clinical trials considered in the present review include both observational and randomized studies. We begin by presenting the studies conducted using non-SARS-CoV-2 specific mAbs for treating different immune disorders that were already on the market. Within this group of mAbs, we focus particularly on anti-IL-6/IL-6R. This is followed by a discussion of the studies on SARS-CoV-2 specific mAbs. Our findings indicate that SARS-CoV-2 specific mAbs are significantly more effective than non-specific ones.
2021-05-26 2021 other review-article; Review; Journal Article abstract-available 10.3390/vaccines9060557 The Relevance of Monoclonal Antibodies in the Treatment of COVID-19. Torrente-López A, Hermosilla J, Navas N, Cuadros-Rodríguez L, Cabeza J, Salmerón-García A. Vaccines (Basel). 2021; 9 (6)
Evaluation of Macular Retinal Vessels and Histological Changes in Two Cases of COVID-19.
Hernandez M, González-Zamora J, Recalde S, Moreno-Orduña M, [...], García-Layana A.
Biomedicines. 2021; 9 (11)
DOI: 10.3390/biomedicines9111546
The purpose of this study was to assess vascular and histological alterations in two COVID-19 and three control post-mortem retinas. The macular areas of flat-mounted samples were processed for immunofluorescence. Lectin and collagen IV positive vessels were captured under confocal microscopy, and endothelium loss and tortuosity were analyzed. Expression of ACE2 (angiotensin-converting enzyme 2) (the receptor for SARS-CoV-2), Iba1 (ionized calcium-binding adaptor molecule 1) and GFAP (glial fibrillary acidic protein) were quantified in retinal sections. The number of lectin vessels in COVID-19 retinas decreased by 27% compared to the control (p < 0.01) and the tortuosity increased in COVID-19 retinas (7.3 ± 0.2) vs. control retinas (6.8 ± 0.07) (p < 0.05). Immunofluorescence analysis revealed an increase in ACE2 (2.3 ± 1.3 vs. 1.0 ± 0.1; p < 0.0001) and Iba1 expression (3.06 ± 0.6 vs. 1.0 ± 0.1; p < 0.01) in COVID-19 sections whereas no changes in GFAP were observed. Analysis of the COVID-19 macular retinal tissue suggested that endothelial cells are a preferential target of SARS-CoV-2 with subsequent changes through their ACE2 receptor expression and morphology. Thus, microglial activation was hyperactive when facing an ensuing immunological challenge after SARS-CoV-2 infection.
2021-10-26 2021 other research-article; Journal Article abstract-available 10.3390/biomedicines9111546 Evaluation of Macular Retinal Vessels and Histological Changes in Two Cases of COVID-19. Hernandez M, González-Zamora J, Recalde S, Moreno-Orduña M, Bilbao-Malavé V, Saenz de Viteri M, Landecho MF, Fernandez-Robredo P, García-Layana A. Biomedicines. 2021; 9 (11)
Insights into the potential role of alpha1-antitrypsin in COVID-19 patients: Mechanisms, current update, and future perspectives.
Marzouk S, Attia N, Mashal M.
Clin Respir J. 2021; 15 (9)
DOI: 10.1111/crj.13406
In this work, we provide an up-to-date summary of the available molecular- and cell-related mechanisms by which alpha1-antitrypsin (AAT) protein could be of benefit in treating COVID-19 patients. As well, we demonstrate the current status in terms of the ongoing clinical trials using AAT in COVID-19 patients. Finally, we touch on the potential role gene therapy and stem cell-based gene therapy could have in such emerging and serious condition caused by the SARS-CoV-2 virus.
2021-07-12 2021 other article-commentary; Journal Article abstract-available 10.1111/crj.13406 Insights into the potential role of alpha1-antitrypsin in COVID-19 patients: Mechanisms, current update, and future perspectives. Marzouk S, Attia N, Mashal M. Clin Respir J. 2021; 15 (9)
Periodically aperiodic pattern of SARS-CoV-2 mutations underpins the uncertainty of its origin and evolution.
Hassan SS, Basu P, Redwan EM, Lundstrom K, [...], Uversky VN.
Environ Res. 2022; 204 (Pt B)
DOI: 10.1016/j.envres.2021.112092
Various lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least 500 in each SARS-CoV-2 protein, we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frame (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in the ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2.
2021-09-22 2021 other research-article; Journal Article abstract-available 10.1016/j.envres.2021.112092 Periodically aperiodic pattern of SARS-CoV-2 mutations underpins the uncertainty of its origin and evolution. Hassan SS, Basu P, Redwan EM, Lundstrom K, Choudhury PP, Serrano-Aroca Á, Azad GK, Aljabali AAA, Palu G, Abd El-Aziz TM, Barh D, Uhal BD, Adadi P, Takayama K, Bazan NG, Tambuwala MM, Lal A, Chauhan G, Baetas-da-Cruz W, Sherchan SP, Uversky VN. Environ Res. 2022; 204 (Pt B)
Performance of a flow cytometry-based immunoassay for detection of antibodies binding to SARS-CoV-2 spike protein.
Valdivia A, Tarín F, Alcaraz MJ, Piñero P, [...], Navarro D.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-021-04565-1
The performance of a laboratory-developed IgG/IgA flow cytometry-based immunoassay (FCI) using Jurkat T cells stably expressing full-length native S protein was compared against Elecsys electrochemiluminiscent (ECLIA) Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), and Liaison SARS-CoV-2 TrimericS IgG chemiluminiscent assay (CLIA) (Diasorin S.p.a, Saluggia, IT) for detection of SARS-CoV-2-specific antibodies. A total of 225 serum/plasma specimens from 120 acute or convalescent COVID-19 individuals were included. Overall, IgG/IgA-FCI yielded the highest number of positives (n = 179), followed by IgA-FCI (n = 177), Roche ECLIA (n = 175), IgG-FCI (n = 172) and Diasorin CLIA (n = 154). For sera collected early after the onset of symptoms (within 15 days) IgG/IgA-FCI also returned the highest number of positive results (52/72; 72.2%). Positive percent agreement between FCI and compared immunoassays was highest for Roche ECLIA, ranging from 96.1 (IgG/IgA-FCI) to 97.7% (IgG-FCI), whereas negative percent agreement was higher between FCI and Diasosin CLIA, regardless of antibody isotype. The data suggest that FCI may outperform Roche ECLIA and Diasorin CLIA in terms of clinical sensitivity for serological diagnosis of SARS-CoV-2 infection.
2022-01-12 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-04565-1 Performance of a flow cytometry-based immunoassay for detection of antibodies binding to SARS-CoV-2 spike protein. Valdivia A, Tarín F, Alcaraz MJ, Piñero P, Torres I, Marco F, Albert E, Navarro D. Sci Rep. 2022; 12 (1)
Efficacy of Phytochemicals Derived from Avicennia officinalis for the Management of COVID-19: A Combined In Silico and Biochemical Study.
Mahmud S, Paul GK, Afroze M, Islam S, [...], Simal-Gandara J.
Molecules. 2021; 26 (8)
DOI: 10.3390/molecules26082210
The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 µg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina. The gas chromatography-mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of -6.75, -6.7, -6.3, and -6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes' binding rigidity in the atomistic simulated environment. However, this study's findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.
2021-04-12 2021 other research-article; Journal Article abstract-available 10.3390/molecules26082210 Efficacy of Phytochemicals Derived from <i>Avicennia officinalis</i> for the Management of COVID-19: A Combined In Silico and Biochemical Study. Mahmud S, Paul GK, Afroze M, Islam S, Gupt SBR, Razu MH, Biswas S, Zaman S, Uddin MS, Khan M, Cacciola NA, Emran TB, Saleh MA, Capasso R, Simal-Gandara J. Molecules. 2021; 26 (8)
Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods.
Ginex T, Garaigorta U, Ramírez D, Castro V, [...], Gil C.
Pharmaceuticals (Basel). 2021; 14 (4)
DOI: 10.3390/ph14040332
The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry-cepharantine, clofazimine, metergoline, imatinib and efloxate-have been identified.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3390/ph14040332 Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods. Ginex T, Garaigorta U, Ramírez D, Castro V, Nozal V, Maestro I, García-Cárceles J, Campillo NE, Martinez A, Gastaminza P, Gil C. Pharmaceuticals (Basel). 2021; 14 (4)
Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review.
Assa A, Benninga MA, Borrelli O, Broekaert I, [...], Gastrointestinal Committee of ESPGHAN.
J Pediatr Gastroenterol Nutr. 2021; 73 (3)
DOI: 10.1097/mpg.0000000000003204

Abstract

Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.
2021-09-01 2021 other review-article; Review; Journal Article abstract-available 10.1097/mpg.0000000000003204 Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review. Assa A, Benninga MA, Borrelli O, Broekaert I, de Carpi JM, Saccomani MD, Dolinsek J, Mas E, Miele E, Thomson M, Tzivinikos C, Gastrointestinal Committee of ESPGHAN. J Pediatr Gastroenterol Nutr. 2021; 73 (3)
Flavonoids against the SARS-CoV-2 induced inflammatory storm.
Liskova A, Samec M, Koklesova L, Samuel SM, [...], Kubatka P.
Biomed Pharmacother. 2021; 138
DOI: 10.1016/j.biopha.2021.111430
The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.
2021-02-25 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.biopha.2021.111430 Flavonoids against the SARS-CoV-2 induced inflammatory storm. Liskova A, Samec M, Koklesova L, Samuel SM, Zhai K, Al-Ishaq RK, Abotaleb M, Nosal V, Kajo K, Ashrafizadeh M, Zarrabi A, Brockmueller A, Shakibaei M, Sabaka P, Mozos I, Ullrich D, Prosecky R, La Rocca G, Caprnda M, Büsselberg D, Rodrigo L, Kruzliak P, Kubatka P. Biomed Pharmacother. 2021; 138
Similarities and differences between HIV and SARS-CoV-2.
Illanes-Álvarez F, Márquez-Ruiz D, Márquez-Coello M, Cuesta-Sancho S, [...], Girón-González JA.
Int J Med Sci. 2021; 18 (3)
DOI: 10.7150/ijms.50133
In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.
2021-01-01 2021 other Historical Article; research-article; Review; Journal Article abstract-available 10.7150/ijms.50133 Similarities and differences between HIV and SARS-CoV-2. Illanes-Álvarez F, Márquez-Ruiz D, Márquez-Coello M, Cuesta-Sancho S, Girón-González JA. Int J Med Sci. 2021; 18 (3)
Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer.
Cattrini C, Bersanelli M, Latocca MM, Conte B, [...], Boccardo F.
Cancers (Basel). 2020; 12 (8)
DOI: 10.3390/cancers12082325
The novel coronavirus disease 2019 (COVID-19) shows a wide spectrum of clinical presentations, severity, and fatality rates. The reason older patients and males show increased risk of severe disease and death remains uncertain. Sex hormones, such as estradiol, progesterone, and testosterone, might be implicated in the age-dependent and sex-specific severity of COVID-19. High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). Data from patients with prostate cancer treated with androgen-deprivation therapy seem to confirm this hypothesis. Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing. Antiandrogens, such as bicalutamide and enzalutamide, are also under investigation. Conversely, other studies suggest that the immune modulating properties of androgens could protect from the unfavorable cytokine storm, and that low testosterone levels might be associated with a worse prognosis in patients with COVID-19. Some evidence also supports the notion that estrogens and progesterone might exert a protective effect on females, through direct antiviral activity or immune-mediated mechanisms, thus explaining the higher COVID-19 severity in post-menopausal women. In this perspective, we discuss the available evidence on sex hormones and hormone therapy in patients infected with SARS-CoV-2, and we highlight the possible implications for cancer patients, who can receive hormonal therapies during their treatment plans.
2020-08-18 2020 other other; Journal Article abstract-available 10.3390/cancers12082325 Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer. Cattrini C, Bersanelli M, Latocca MM, Conte B, Vallome G, Boccardo F. Cancers (Basel). 2020; 12 (8)
Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium.
Gorog DA, Storey RF, Gurbel PA, Tantry US, [...], Becker RC.
Nat Rev Cardiol. 2022;
DOI: 10.1038/s41569-021-00665-7
Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available 10.1038/s41569-021-00665-7 Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium. Gorog DA, Storey RF, Gurbel PA, Tantry US, Berger JS, Chan MY, Duerschmied D, Smyth SS, Parker WAE, Ajjan RA, Vilahur G, Badimon L, Berg JMT, Cate HT, Peyvandi F, Wang TT, Becker RC. Nat Rev Cardiol. 2022;
Persistence of SARS-CoV-2 infection on personal protective equipment (PPE).
Córdoba-Lanús E, García-Pérez O, Cazorla-Rivero S, Rodríguez-Esparragón F, [...], Lorenzo-Morales J.
BMC Infect Dis. 2021; 21 (1)
DOI: 10.1186/s12879-021-06861-7

Background

SARS-CoV-2 stability and infection persistence has been studied on different surfaces, but scarce data exist related to personal protective equipment (PPE), moreover using realist viral loads for infection. Due to the importance for adequate PPE management to avoid risk of virus infection, RNA stability was evaluated on PPE.

Methods

Persistence of SARS-CoV-2 infection and detection of genomic RNA in PPE (gowns and face masks) were determined by in-vitro assays and RT-qPCR, respectively. Samples were infected with a clinical sample positive for SARS-CoV-2 (Clin-Inf), and with a heat-inactivated SARS-CoV-2 strain sample (Str-Inf) as a control.

Results

PPE samples infected with Clin-Inf were positive for the 3 viral genes on gowns up to 5 days post-infection, whereas these overall genes were detected up to 30 days in the case of face masks. However, gowns and FFP2 masks samples contaminated with Clin-Inf showed a cytopathic effect over VERO cells up to 5-7 days post-infection.

Conclusions

SARS-CoV-2 RNA was detected on different PPE materials for 5 to 30 days, but PPE contaminated with the virus was infectious up to 5-7 days. These findings demonstrate the need to improve PPE management and to formulate strategies to introduce viricidal compounds in PPE fabrics.
2021-11-19 2021 other research-article; Journal Article abstract-available 10.1186/s12879-021-06861-7 Persistence of SARS-CoV-2 infection on personal protective equipment (PPE). Córdoba-Lanús E, García-Pérez O, Cazorla-Rivero S, Rodríguez-Esparragón F, Piñero JE, Clavo B, Lorenzo-Morales J. BMC Infect Dis. 2021; 21 (1)
COVID-19 and COPD: lessons beyond the pandemic.
Halpin DMG, Vogelmeier CF, Agusti A.
Am J Physiol Lung Cell Mol Physiol. 2021; 321 (5)
DOI: 10.1152/ajplung.00386.2021
Early in the COVID pandemic there were concerns about the outcomes for patients with COPD who developed COVID-19. Although the pandemic has made the diagnosis and routine management of COPD more difficult, the risk of patients developing COVID or of having poor outcomes is less than anticipated and there have been some unexpected findings that may lead to significant improvements in the management of COPD in future.
2021-09-29 2021 other Comment; Editorial abstract-available 10.1152/ajplung.00386.2021 COVID-19 and COPD: lessons beyond the pandemic. Halpin DMG, Vogelmeier CF, Agusti A. Am J Physiol Lung Cell Mol Physiol. 2021; 321 (5)
High prevalence of SARS-CoV-2 infection in patients scheduled for digestive endoscopy after the peak of the first wave of the pandemic☆ Alta prevalencia de infección por SARS-CoV-2 en pacientes programados para endoscopia digestiva después del pico de la primera onda pandémica
Pamplona J, Solano R, Ramírez M, Durandez R, [...], Sàbat M.
Gastroenterología y Hepatología (English Edition). 2021; 44 (9)
DOI:
Healthcare professionals in endoscopy units have a possible risk of SARS-CoV-2 infection by different routes: inhalation of airborne droplets, aerosols, conjunctival contact and faecal-oral transmission.

Objective

To describe the detection of SARS-CoV-2 in a series of patients scheduled for digestive endoscopy at the Hospital Santa Caterina, Salt, (Girona).

Methods

Descriptive study of a series of cases of patients scheduled for endoscopy during the month of May 2020, when endoscopic activity was resumed after the peak of the pandemic, following SCD, SEED, AEG and ESGE recommendations. We examined nasopharyngeal samples 48−72 h before the appointment, by RT-PCR, in all patients. RNA extraction was performed using the kits: Qiagen®-adapted, BiosSprint®96-DNA-Blood-Kit (384). For amplification-detection of SARS-CoV-2, methods recommended by the WHO and the CDC were followed.

Results

110 asymptomatic patients without close contact with a positive case in the previous 14 days were scheduled; 105 (96.4%) were negative and five (4.5%) were positive. Two patients developed respiratory symptoms after diagnosis (presymptomatic) and three remained asymptomatic. Allfive5 patients were autochthonous cases with no history of travel or residence in another city or country associated with high prevalence of infection. Four cases were women aged 60–81 years. The N gene was detected in all cases.

Conclusions

A high prevalence of SARS-CoV-2 infection was detected in patients scheduled for digestive endoscopy. Given the risk of transmission to professionals, we consider it advisable to perform SARS-CoV-2 RT-PCR 48−72 h before the examination in situations of high incidence in the population.
2021-09-14 2021 other research-article; Journal Article abstract-available High prevalence of SARS-CoV-2 infection in patients scheduled for digestive endoscopy after the peak of the first wave of the pandemic☆ Alta prevalencia de infección por SARS-CoV-2 en pacientes programados para endoscopia digestiva después del pico de la primera onda pandémica Pamplona J, Solano R, Ramírez M, Durandez R, Mohamed F, Pardo L, Sàbat M. Gastroenterología y Hepatología (English Edition). 2021; 44 (9)
Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis.
Rico-Martín S, Calderón-García JF, Basilio-Fernández B, Clavijo-Chamorro MZ, [...], Sánchez Muñoz-Torrero JF.
J Cardiovasc Dev Dis. 2021; 8 (12)
DOI: 10.3390/jcdd8120162
Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients.

Methods

A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale.

Results

The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88-3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16-4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71-2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed.

Conclusions

this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components.
2021-11-25 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcdd8120162 Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis. Rico-Martín S, Calderón-García JF, Basilio-Fernández B, Clavijo-Chamorro MZ, Sánchez Muñoz-Torrero JF. J Cardiovasc Dev Dis. 2021; 8 (12)
Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study.
Kirkegaard C, Falcó-Roget A, Sánchez-Montalvá A, Valls Á, [...], Len Ò.
Infection. 2021;
DOI: 10.1007/s15010-021-01662-1

Purpose

We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19.

Methods

We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission.

Conclusion

Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.
2021-07-30 2021 other research-article; Journal Article abstract-available 10.1007/s15010-021-01662-1 Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study. Kirkegaard C, Falcó-Roget A, Sánchez-Montalvá A, Valls Á, Clofent D, Campos-Varela I, García-García S, Leguízamo LM, Sellarès-Nadal J, Eremiev S, Villamarín M, Marzo B, Almirante B, Len Ò. Infection. 2021;
Pharmacological Treatments against COVID-19 in Pregnant Women.
Arco-Torres A, Cortés-Martín J, Tovar-Gálvez MI, Montiel-Troya M, [...], Rodríguez-Blanque R.
J Clin Med. 2021; 10 (21)
DOI: 10.3390/jcm10214896
The recent respiratory virus known as SARS-CoV-2 has caused millions of deaths worldwide, causing great uncertainty due to the lack of a specific treatment, which has been mitigated by the use of various drugs traditionally used against other types of pathologies. Pregnancy presents special physiological conditions that expose the pregnant woman and the foetus to greater risk. Pregnant women are often excluded from trials due to possible risk of toxicity or side effects, resulting in a lack of knowledge about the use of drugs and treatments during pregnancy. The main objective of this review was to compile existing knowledge about currently available drug treatments for COVID-19 in pregnant women. The review report met the criteria of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) review protocol and was registered with the registration number CRD42021251036. The electronic databases searched were Scopus, PubMed, CINAHL and SciELO. Finally, 22 articles were included, resulting in an analysis of drugs with an acceptable safety profile in the treatment of pregnant women with COVID-19.
2021-10-24 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcm10214896 Pharmacological Treatments against COVID-19 in Pregnant Women. Arco-Torres A, Cortés-Martín J, Tovar-Gálvez MI, Montiel-Troya M, Riquelme-Gallego B, Rodríguez-Blanque R. J Clin Med. 2021; 10 (21)
DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?
Valencia I, Peiró C, Lorenzo Ó, Sánchez-Ferrer CF, [...], Romacho T.
Front Pharmacol. 2020; 11
DOI: 10.3389/fphar.2020.01161
COVID-19 outbreak, caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus has become an urgent health and economic challenge. Diabetes is a risk factor for severity and mortality of COVID-19. Recent studies support that COVID-19 has effects beyond the respiratory tract, with vascular complications arising as relevant factors worsening its prognosis, then making patients with previous vascular disease more prone to severity or fatal outcome. Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. SARS-CoV-2 might use other co-receptor or auxiliary proteins allowing virus infection. In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. The renin-angiotensin-aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications. Diabetes affects more than 400 million people worldwide, thus better understanding of how they are affected by COVID-19 holds an important benefit to fight against this disease with pandemic proportions.
2020-08-07 2020 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2020.01161 DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications? Valencia I, Peiró C, Lorenzo Ó, Sánchez-Ferrer CF, Eckel J, Romacho T. Front Pharmacol. 2020; 11
Superspreading in the emergence of COVID-19 variants.
Gómez-Carballa A, Pardo-Seco J, Bello X, Martinón-Torres F, [...], Salas A.
Trends Genet. 2021; 37 (12)
DOI: 10.1016/j.tig.2021.09.003
Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success.
2021-09-08 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.tig.2021.09.003 Superspreading in the emergence of COVID-19 variants. Gómez-Carballa A, Pardo-Seco J, Bello X, Martinón-Torres F, Salas A. Trends Genet. 2021; 37 (12)
One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages.
González-Candelas F, Shaw MA, Phan T, Kulkarni-Kale U, [...], Sironi M.
Infect Genet Evol. 2021; 92
DOI: 10.1016/j.meegid.2021.104869
The COVID-19 pandemic was officially declared on March 11th, 2020. Since the very beginning, the spread of the virus has been tracked nearly in real-time by worldwide genome sequencing efforts. As of March 2021, more than 830,000 SARS-CoV-2 genomes have been uploaded in GISAID and this wealth of data allowed researchers to study the evolution of SARS-CoV-2 during this first pandemic year. In parallel, nomenclatures systems, often with poor consistency among each other, have been developed to designate emerging viral lineages. Despite general fears that the virus might mutate to become more virulent or transmissible, SARS-CoV-2 genetic diversity has remained relatively low during the first ~ 8 months of sustained human-to-human transmission. At the end of 2020/beginning of 2021, though, some alarming events started to raise concerns of possible changes in the evolutionary trajectory of the virus. Specifically, three new viral variants associated with extensive transmission have been described as variants of concern (VOC). These variants were first reported in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Their designation as VOCs was determined by an increase of local cases and by the high number of amino acid substitutions harboured by these lineages. This latter feature is reminiscent of viral sequences isolated from immunocompromised patients with long-term infection, suggesting a possible causal link. Here we review the events that led to the identification of these lineages, as well as emerging data concerning their possible implications for viral phenotypes, reinfection risk, vaccine efficiency and epidemic potential. Most of the available evidence is, to date, provisional, but still represents a starting point to uncover the potential threat posed by the VOCs. We also stress that genomic surveillance must be strengthened, especially in the wake of the vaccination campaigns.
2021-04-26 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.meegid.2021.104869 One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages. González-Candelas F, Shaw MA, Phan T, Kulkarni-Kale U, Paraskevis D, Luciani F, Kimura H, Sironi M. Infect Genet Evol. 2021; 92
Current state of diagnostic, screening and surveillance testing methods for COVID-19 from an analytical chemistry point of view.
Martín J, Tena N, Asuero AG.
Microchem J. 2021; 167
DOI: 10.1016/j.microc.2021.106305
Since December 2019, we have been in the battlefield with a new threat to the humanity known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we describe the four main methods used for diagnosis, screening and/or surveillance of SARS-CoV-2: Real-time reverse transcription polymerase chain reaction (RT-PCR); chest computed tomography (CT); and different complementary alternatives developed in order to obtain rapid results, antigen and antibody detection. All of them compare the highlighting advantages and disadvantages from an analytical point of view. The gold standard method in terms of sensitivity and specificity is the RT-PCR. The different modifications propose to make it more rapid and applicable at point of care (POC) are also presented and discussed. CT images are limited to central hospitals. However, being combined with RT-PCR is the most robust and accurate way to confirm COVID-19 infection. Antibody tests, although unable to provide reliable results on the status of the infection, are suitable for carrying out maximum screening of the population in order to know the immune capacity. More recently, antigen tests, less sensitive than RT-PCR, have been authorized to determine in a quicker way whether the patient is infected at the time of analysis and without the need of specific instruments.
2021-04-19 2021 other research-article; Journal Article abstract-available 10.1016/j.microc.2021.106305 Current state of diagnostic, screening and surveillance testing methods for COVID-19 from an analytical chemistry point of view. Martín J, Tena N, Asuero AG. Microchem J. 2021; 167
New statistical model for misreported data with application to current public health challenges.
Moriña D, Fernández-Fontelo A, Cabaña A, Puig P.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-02620-5
The main goal of this work is to present a new model able to deal with potentially misreported continuous time series. The proposed model is able to handle the autocorrelation structure in continuous time series data, which might be partially or totally underreported or overreported. Its performance is illustrated through a comprehensive simulation study considering several autocorrelation structures and three real data applications on human papillomavirus incidence in Girona (Catalonia, Spain) and Covid-19 incidence in two regions with very different circumstances: the early days of the epidemic in the Chinese region of Heilongjiang and the most current data from Catalonia.
2021-12-02 2021 fondo-covid Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-02620-5 New statistical model for misreported data with application to current public health challenges. Moriña D, Fernández-Fontelo A, Cabaña A, Puig P. Sci Rep. 2021; 11 (1)
Disinfectant-induced hormesis: An unknown environmental threat of the application of disinfectants to prevent SARS-CoV-2 infection during the COVID-19 pandemic?
Agathokleous E, Barceló D, Iavicoli I, Tsatsakis A, [...], Calabrese EJ.
Environ Pollut. 2022; 292 (Pt B)
DOI: 10.1016/j.envpol.2021.118429
Massive additional quantities of disinfectants have been applied during the COVID-19 pandemic as infection preventive and control measures. While the application of disinfectants plays a key role in preventing the spread of SARS-CoV-2 infection, the effects of disinfectants applied during the ongoing pandemic on non-target organisms remain unknown. Here we collated evidence from multiple studies showing that chemicals used for major disinfectant products can induce hormesis in various organisms, such as plants, animal cells, and microorganisms, when applied singly or in mixtures, suggesting potential ecological risks at sub-threshold doses that are normally considered safe. Among other effects, sub-threshold doses of disinfectant chemicals can enhance the proliferation and pathogenicity of pathogenic microbes, enhancing the development and spread of drug resistance. We opine that hormesis should be considered when evaluating the effects and risks of such disinfectants, especially since the linear-no-threshold (LNT) and threshold dose-response models cannot identify or predict their effects.
2021-10-29 2021 other brief-report; Journal Article abstract-available 10.1016/j.envpol.2021.118429 Disinfectant-induced hormesis: An unknown environmental threat of the application of disinfectants to prevent SARS-CoV-2 infection during the COVID-19 pandemic? Agathokleous E, Barceló D, Iavicoli I, Tsatsakis A, Calabrese EJ. Environ Pollut. 2022; 292 (Pt B)
Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE.
Lam SD, Ashford P, Díaz-Sánchez S, Villar M, [...], Orengo C.
Viruses. 2021; 13 (4)
DOI: 10.3390/v13040708
Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts.
2021-04-19 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13040708 Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE. Lam SD, Ashford P, Díaz-Sánchez S, Villar M, Gortázar C, de la Fuente J, Orengo C. Viruses. 2021; 13 (4)
SARS-CoV-2 in Conjunctiva and Tears and Ocular Symptoms of Patients with COVID-19.
Rodríguez-Ares T, Lamas-Francis D, Treviño M, Navarro D, [...], Touriño R.
Vision (Basel). 2021; 5 (4)
DOI: 10.3390/vision5040051
This study investigates the presence of SARS-CoV-2 in conjunctival secretions and tears and evaluates ocular symptoms in a group of patients with COVID-19. We included 56 hospitalized patients with COVID-19 in this cross-sectional cohort study. Conjunctival secretions and tears were collected using flocked swabs and Schirmer strips for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR). Assessment of ocular surface manifestations included an OSDI (Ocular Surface Disease Index) questionnaire. Patients had been admitted to hospital for an average of 2.4 days (range 0-7) and had shown general symptoms for an average of 7.1 days (range 1-20) prior to ocular testing. Four (7.1%) of 56 conjunctival swabs and four (4%) of 112 Schirmer strips were positive for SARS-CoV-2. The mean E-gene cycle threshold values (Ct values) were 31.2 (SD 5.0) in conjunctival swabs and 32.9 (SD 2.7) in left eye Schirmer strips. Overall, 17 (30%) patients presented ocular symptoms. No association was found between positive ocular samples and ocular symptoms. This study shows that SARS-CoV-2 can be detected on the conjunctiva and tears of patients with COVID-19. Contact with the ocular surface may transmit the virus and preventive measures should be taken in this direction.
2021-10-22 2021 other research-article; Journal Article abstract-available 10.3390/vision5040051 SARS-CoV-2 in Conjunctiva and Tears and Ocular Symptoms of Patients with COVID-19. Rodríguez-Ares T, Lamas-Francis D, Treviño M, Navarro D, Cea M, López-Valladares MJ, Martínez L, Gude F, Touriño R. Vision (Basel). 2021; 5 (4)
A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo.
Hanke L, Das H, Sheward DJ, Perez Vidakovics L, [...], McInerney GM.
Nat Commun. 2022; 13 (1)
DOI: 10.1038/s41467-021-27610-z
Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we describe the isolation of a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer-dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the beta and delta variants, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the beta variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes an uncommon strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants.
2022-01-10 2022 other Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1038/s41467-021-27610-z A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo. Hanke L, Das H, Sheward DJ, Perez Vidakovics L, Urgard E, Moliner-Morro A, Kim C, Karl V, Pankow A, Smith NL, Porebski B, Fernandez-Capetillo O, Sezgin E, Pedersen GK, Coquet JM, Hällberg BM, Murrell B, McInerney GM. Nat Commun. 2022; 13 (1)
Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2.
Sanclemente-Alaman I, Moreno-Jiménez L, Benito-Martín MS, Canales-Aguirre A, [...], Gómez-Pinedo U.
Front Immunol. 2020; 11
DOI: 10.3389/fimmu.2020.02163

Introduction

The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions.

Development

We reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids.

Conclusion

Given the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.
2020-08-28 2020 other review-article; Review; Journal Article abstract-available 10.3389/fimmu.2020.02163 Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2. Sanclemente-Alaman I, Moreno-Jiménez L, Benito-Martín MS, Canales-Aguirre A, Matías-Guiu JA, Matías-Guiu J, Gómez-Pinedo U. Front Immunol. 2020; 11
Lack of Effectiveness of Repurposed Drugs for COVID-19 Treatment.
Martinez MA.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.635371
2021-03-11 2021 other discussion; Journal Article 10.3389/fimmu.2021.635371 Lack of Effectiveness of Repurposed Drugs for COVID-19 Treatment. Martinez MA. Front Immunol. 2021; 12
Heart rate at presentation of COVID-19: Can SARS-CoV-2 be a cause of dysautonomia?
Sánchez AS, Rey JR, Iniesta ÁM, Merino JL, [...], Caro-Codón J.
Rev Port Cardiol. 2021;
DOI: 10.1016/j.repc.2021.07.010
2021-11-20 2021 other letter; Journal Article 10.1016/j.repc.2021.07.010 Heart rate at presentation of COVID-19: Can SARS-CoV-2 be a cause of dysautonomia? Sánchez AS, Rey JR, Iniesta ÁM, Merino JL, Castrejón-Castrejón S, López-de-Sá E, Caro-Codón J. Rev Port Cardiol. 2021;
A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
Monserrat Villatoro J, Mejía-Abril G, Díaz García L, Zubiaur P, [...], on behalf of the COVID@HULP Working Group and Other Collaborators from Hospital Universitario de la Princesa.
Pharmaceuticals (Basel). 2022; 15 (1)
DOI:
Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions.
2022-01-01 2022 other research-article; Journal Article abstract-available A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis Monserrat Villatoro J, Mejía-Abril G, Díaz García L, Zubiaur P, Jiménez González M, Fernandez Jimenez G, Cancio I, Arribas J, Suarez Fernández C, Mingorance J, García Rodríguez J, Villagrasa Ferrer J, Carcas A, Frías J, Abad-Santos F, Borobia A, Ramírez E, on behalf of the COVID@HULP Working Group and Other Collaborators from Hospital Universitario de la Princesa. Pharmaceuticals (Basel). 2022; 15 (1)
Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.
Prieto-Fernández E, Egia-Mendikute L, Vila-Vecilla L, Bosch A, [...], Palazon A.
Emerg Microbes Infect. 2021; 10 (1)
DOI: 10.1080/22221751.2021.1932607
A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1α-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1080/22221751.2021.1932607 Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate. Prieto-Fernández E, Egia-Mendikute L, Vila-Vecilla L, Bosch A, Barreira-Manrique A, Lee SY, García-Del Río A, Antoñana-Vildosola A, Jiménez-Lasheras B, Moreno-Cugnon L, Jiménez-Barbero J, Berra E, Ereño-Orbea J, Palazon A. Emerg Microbes Infect. 2021; 10 (1)
SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants.
Pruimboom L.
Med Hypotheses. 2021; 146
DOI: 10.1016/j.mehy.2020.110368
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highjacks epithelial cells and infiltrates the lung, as well as other organs and tissues, is essential for developing treatment strategies and vaccines against this highly contagious virus. Another major goal is to fully elucidate the mechanisms by which SARS-CoV- 2 bypasses the innate immune system and induces a cytokine storm, and its effects on mortality. Currently, SARS- CoV-2 is thought to evade innate antiviral immunity, undergo endocytosis, and fuse with the host cell membrane by exploiting ACE2 receptors and the protease TMMPRSS2, with cathepsin B/L as alternative protease, for entry into the epithelial cells of tissues vulnerable to developing coronavirus disease 2019 (COVID-19) symptoms. However, the incorporation of new and unique binding sites, i.e., O-linked glycans, and the preservation and augmentation of effective binding sites (N-linked glycans) on the outer membrane of SARS-CoV-2 may represent other strategies of infecting the human host. Here, I will rationalize the possibility that other host molecules-i.e., sugar molecules and the sialic acidsN-glycolylneuraminic acid, N-acetylneuraminic acid, and their derivates could be viable candidates for the use as virus receptors by SARS-CoV-2 and/or serve as determinants for the adherence on ACE2 of SARS-CoV-2.
2020-11-06 2020 other research-article; Review; Journal Article abstract-available 10.1016/j.mehy.2020.110368 SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants. Pruimboom L. Med Hypotheses. 2021; 146
Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol.
Arévalos V, Ortega-Paz L, Fernandez-Rodríguez D, Alfonso Jiménez-Díaz V, [...], CV COVID-19 Registry Investigators.
PLoS One. 2021; 16 (7)
DOI: 10.1371/journal.pone.0255263

Background

Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes.

Study and design

This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee.

Conclusion

The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.
2021-07-29 2021 fondo-covid Clinical Trial; Research Support, Non-U.S. Gov't; research-article; Multicenter Study; Journal Article; Observational Study abstract-available 10.1371/journal.pone.0255263 Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol. Arévalos V, Ortega-Paz L, Fernandez-Rodríguez D, Alfonso Jiménez-Díaz V, Rius JB, Campo G, Rodríguez-Santamarta M, de Prado AP, Gómez-Menchero A, Díaz Fernández JF, Scardino C, Gonzalo N, Pernigotti A, Alfonso F, Jesús Amat-Santos I, Silvestro A, Ielasi A, María de la Torre J, Bastidas G, Gómez-Lara J, Sabaté M, Brugaletta S, CV COVID-19 Registry Investigators. PLoS One. 2021; 16 (7)
Small Resistance Artery Disease and ACE2 in Hypertension: A New Paradigm in the Context of COVID-19.
Galán M, Jiménez-Altayó F.
Front Cardiovasc Med. 2020; 7
DOI: 10.3389/fcvm.2020.588692
Cardiovascular disease causes almost one third of deaths worldwide, and more than half are related to primary arterial hypertension (PAH). The occurrence of several deleterious events, such as hyperactivation of the renin-angiotensin system (RAS), and oxidative and inflammatory stress, contributes to the development of small vessel disease in PAH. Small resistance arteries are found at various points through the arterial tree, act as the major site of vascular resistance, and actively regulate local tissue perfusion. Experimental and clinical studies demonstrate that alterations in small resistance artery properties are important features of PAH pathophysiology. Diseased small vessels in PAH show decreased lumens, thicker walls, endothelial dysfunction, and oxidative stress and inflammation. These events may lead to altered blood flow supply to tissues and organs, and can increase the risk of thrombosis. Notably, PAH is prevalent among patients diagnosed with COVID-19, in whom evidence of small vessel disease leading to cardiovascular pathology is reported. The SARS-Cov2 virus, responsible for COVID-19, achieves cell entry through an S (spike) high-affinity protein binding to the catalytic domain of the angiotensin-converting enzyme 2 (ACE2), a negative regulator of the RAS pathway. Therefore, it is crucial to examine the relationship between small resistance artery disease, ACE2, and PAH, to understand COVID-19 morbidity and mortality. The scope of the present review is to briefly summarize available knowledge on the role of small resistance artery disease and ACE2 in PAH, and critically discuss their clinical relevance in the context of cardiovascular pathology associated to COVID-19.
2020-10-30 2020 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2020.588692 Small Resistance Artery Disease and ACE2 in Hypertension: A New Paradigm in the Context of COVID-19. Galán M, Jiménez-Altayó F. Front Cardiovasc Med. 2020; 7
Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI).
Sokolowska M, Lukasik ZM, Agache I, Akdis CA, [...], Untersmayr E.
Allergy. 2020; 75 (10)
DOI: 10.1111/all.14462
With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.
2020-10-01 2020 other research-article; Review; Journal Article abstract-available 10.1111/all.14462 Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI). Sokolowska M, Lukasik ZM, Agache I, Akdis CA, Akdis D, Akdis M, Barcik W, Brough HA, Eiwegger T, Eljaszewicz A, Eyerich S, Feleszko W, Gomez-Casado C, Hoffmann-Sommergruber K, Janda J, Jiménez-Saiz R, Jutel M, Knol EF, Kortekaas Krohn I, Kothari A, Makowska J, Moniuszko M, Morita H, O'Mahony L, Nadeau K, Ozdemir C, Pali-Schöll I, Palomares O, Papaleo F, Prunicki M, Schmidt-Weber CB, Sediva A, Schwarze J, Shamji MH, Tramper-Stranders GA, van de Veen W, Untersmayr E. Allergy. 2020; 75 (10)
Is asthma a risk factor for COVID-19? Are phenotypes important?
Muñoz X, Pilia F, Ojanguren I, Romero-Mesones C, [...], Cruz MJ.
ERJ Open Res. 2021; 7 (1)
DOI: 10.1183/23120541.00216-2020
These results reaffirm the idea that asthma does not appear to be a risk factor for the development of #COVID19. However, most of the asthma patients in this study had a non-T2 phenotype. https://bit.ly/38hIp18.
2021-01-25 2021 other letter; Journal Article abstract-available 10.1183/23120541.00216-2020 Is asthma a risk factor for COVID-19? Are phenotypes important? Muñoz X, Pilia F, Ojanguren I, Romero-Mesones C, Cruz MJ. ERJ Open Res. 2021; 7 (1)
Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients
Beraud M, Goodhue Meyer E, Lozano M, Bah A, [...], Brown B.
Transfus Apher Sci. 2022;
DOI:
Coronavirus disease 2019 (COVID-19) convalescent plasma (CovCP) infusions have been widely used for the treatment of hospitalized patients with COVID-19. The aims of this narrative review were to analyze the safety and efficacy of CovCP infusions in the overall population and in immunocompromised patients with COVID-19 and to identify the lessons learned concerning the use of convalescent plasma (CP) to fill treatment gaps for emerging viruses. Systematic searches (PubMed, Scopus, and COVID-19 Research) were conducted to identify peer-reviewed articles and pre-prints published between March 1, 2020 and May 1, 2021 on the use of CovCP for the treatment of patients with COVID-19. From 261 retrieved articles, 37 articles reporting robust controlled studies in the overall population of patients with COVID-19 and 9 articles in immunocompromised patients with COVID-19 were selected. While CovCP infusions are well tolerated in both populations, they do not seem to improve clinical outcomes in critically-ill patients with COVID-19 and no conclusion could be drawn concerning their potential benefits in immunocompromised patients with COVID-19. To be better prepared for future epidemics/pandemics and to evaluate potential benefits of CP treatment, only CP units with high neutralizing antibodies (NAbs) titers should be infused in patients with low NAb titers, patient eligibility criteria should be based on the disease pathophysiology, and measured clinical outcomes and methods should be comparable across studies. Even if CovCP infusions did not improve clinical outcomes in patients with COVID-19, NAb-containing CP infusions remain a safe, widely available and potentially beneficial treatment option for future epidemics/pandemics.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients Beraud M, Goodhue Meyer E, Lozano M, Bah A, Vassallo R, Brown B. Transfus Apher Sci. 2022;
Retrospective screening for SARS-CoV-2 among influenza-like illness hospitalizations: 2018-2019 and 2019-2020 seasons, Valencia region, Spain.
Mira-Iglesias A, Mengual-Chuliá B, Cano L, García-Rubio J, [...], López-Labrador FX.
Influenza Other Respir Viruses. 2022; 16 (1)
DOI: 10.1111/irv.12899
On 9 March 2020, the World Health Organization (WHO) Global Influenza Programme (GIP) asked participant sites on the Global Influenza Hospital Surveillance Network (GIHSN) to contribute to data collection concerning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We re-analysed 5833 viral RNA archived samples collected prospectively from hospital admissions for influenza-like illness (ILI) in the Valencia Region of Spain by the Valencia Hospital Surveillance Network for the Study of Influenza and Other Respiratory Viruses (VAHNSI) network (four hospitals, catchment area population 1 118 732) during the pre-pandemic 2018/2019 (n = 4010) and pandemic 2019/2020 (n = 1823) influenza seasons for the presence of SARS-CoV-2. We did not find evidence for community-acquired SARS-CoV-2 infection in hospital admissions for ILI in our region before early March 2020.
2021-09-16 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1111/irv.12899 Retrospective screening for SARS-CoV-2 among influenza-like illness hospitalizations: 2018-2019 and 2019-2020 seasons, Valencia region, Spain. Mira-Iglesias A, Mengual-Chuliá B, Cano L, García-Rubio J, Tortajada-Girbés M, Carballido-Fernández M, Mollar-Maseres J, Schwarz-Chavarri G, García-Esteban S, Puig-Barberà J, Díez-Domingo J, López-Labrador FX. Influenza Other Respir Viruses. 2022; 16 (1)
Facial Nerve Palsy as a Neurological Manifestation of COVID-19.
Martins ASP, Losa FJF, Rueda HHV, García-Gasalla M.
J Glob Infect Dis. 2021; 13 (4)
DOI: 10.4103/jgid.jgid_360_20
Facial nerve palsy is the most frequent acute mononeuropathy and it is often of viral etiology, although many other causes have been identified. It has recently been described as a potential manifestation of COVID-19. We report the case of a patient with recent history of diarrhea and malaise that was admitted to the hospital presenting right facial paresis with orbicular muscle involvement. Nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the real-time reverse transcription polymerase chain reaction and magnetic resonance imaging showed no structural changes. During the hospital stay, the patient showed clinical improvement, and no other symptoms were observed. This case presentation suggests a possible association between neuropathies and SARS-CoV-2 infection.
2021-08-07 2021 other Case Reports; case-report abstract-available 10.4103/jgid.jgid_360_20 Facial Nerve Palsy as a Neurological Manifestation of COVID-19. Martins ASP, Losa FJF, Rueda HHV, García-Gasalla M. J Glob Infect Dis. 2021; 13 (4)
Rapid SARS-CoV-2 Inactivation in a Simulated Hospital Room Using a Mobile and Autonomous Robot Emitting Ultraviolet-C Light.
Lorca-Oró C, Vila J, Pleguezuelos P, Vergara-Alert J, [...], Abad X.
J Infect Dis. 2021;
DOI: 10.1093/infdis/jiab551
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has made mask-wearing, physical distancing, hygiene, and disinfection complementary measures to control virus transmission. Especially for health facilities, we evaluated the efficacy of an UV-C autonomous robot to inactivate SARS-CoV-2 desiccated on potentially contaminated surfaces. ASSUM (autonomous sanitary sterilization ultraviolet machine) robot was used in an experimental box simulating a hospital intensive care unit room. Desiccated SARS-CoV-2 samples were exposed to UV-C in 2 independent runs of 5, 12, and 20 minutes. Residual virus was eluted from surfaces and viral titration was carried out in Vero E6 cells. ASSUM inactivated SARS-CoV-2 by ≥ 99.91% to ≥ 99.99% titer reduction with 12 minutes or longer of UV-C exposure and onwards and a minimum distance of 100cm between the device and the SARS-CoV-2 desiccated samples. This study demonstrates that ASSUM UV-C device is able to inactivate SARS-CoV-2 within a few minutes.
2021-11-20 2021 other research-article; Journal Article abstract-available 10.1093/infdis/jiab551 Rapid SARS-CoV-2 Inactivation in a Simulated Hospital Room Using a Mobile and Autonomous Robot Emitting Ultraviolet-C Light. Lorca-Oró C, Vila J, Pleguezuelos P, Vergara-Alert J, Rodon J, Majó N, López S, Segalés J, Saldaña-Buesa F, Visa-Boladeras M, Veà-Baró A, Campistol JM, Abad X. J Infect Dis. 2021;
The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome.
Battaglini D, Robba C, Fedele A, Trancǎ S, [...], Pelosi P.
Front Med (Lausanne). 2021; 8
DOI: 10.3389/fmed.2021.671714
In late December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) quickly spread worldwide, and the syndrome it causes, coronavirus disease 2019 (COVID-19), has reached pandemic proportions. Around 30% of patients with COVID-19 experience severe respiratory distress and are admitted to the intensive care unit for comprehensive critical care. Patients with COVID-19 often present an enhanced immune response with a hyperinflammatory state characterized by a "cytokine storm," which may reflect changes in the microbiota composition. Moreover, the evolution to acute respiratory distress syndrome (ARDS) may increase the severity of COVID-19 and related dysbiosis. During critical illness, the multitude of therapies administered, including antibiotics, sedatives, analgesics, body position, invasive mechanical ventilation, and nutritional support, may enhance the inflammatory response and alter the balance of patients' microbiota. This status of dysbiosis may lead to hyper vulnerability in patients and an inappropriate response to critical circumstances. In this context, the aim of our narrative review is to provide an overview of possible interaction between patients' microbiota dysbiosis and clinical status of severe COVID-19 with ARDS, taking into consideration the characteristic hyperinflammatory state of this condition, respiratory distress, and provide an overview on possible nutritional strategies for critically ill patients with COVID-19-ARDS.
2021-06-04 2021 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2021.671714 The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome. Battaglini D, Robba C, Fedele A, Trancǎ S, Sukkar SG, Di Pilato V, Bassetti M, Giacobbe DR, Vena A, Patroniti N, Ball L, Brunetti I, Torres Martí A, Rocco PRM, Pelosi P. Front Med (Lausanne). 2021; 8
Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
Gutiérrez-Álvarez J, Honrubia JM, Sanz-Bravo A, González-Miranda E, [...], Enjuanes L.
Proc Natl Acad Sci U S A. 2021; 118 (43)
DOI: 10.1073/pnas.2111075118
Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.
2021-10-01 2021 other research-article; Journal Article abstract-available 10.1073/pnas.2111075118 Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice. Gutiérrez-Álvarez J, Honrubia JM, Sanz-Bravo A, González-Miranda E, Fernández-Delgado R, Rejas MT, Zúñiga S, Sola I, Enjuanes L. Proc Natl Acad Sci U S A. 2021; 118 (43)
Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target.
García-Dorival I, Cuesta-Geijo MÁ, Barrado-Gil L, Galindo I, [...], Alonso C.
Antiviral Res. 2021; 194
DOI: 10.1016/j.antiviral.2021.105167
Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol traffic. This protein has been shown to play an important role for several viruses. It has been reported that SARS-CoV-2 enters the cell through plasma membrane fusion and/or endosomal entry upon availability of proteases. However, the whole process is not fully understood yet and additional viral/host factors might be required for viral fusion and subsequent viral replication. Here, we report a novel interaction between the SARS-CoV-2 nucleoprotein (N) and the cholesterol transporter NPC1. Furthermore, we have found that some compounds reported to interact with NPC1, carbazole SC816 and sulfides SC198 and SC073, were able to reduce SARS-CoV-2 viral infection with a good selectivity index in human cell infection models. These findings suggest the importance of NPC1 for SARS-CoV-2 viral infection and a new possible potential therapeutic target to fight against COVID-19.
2021-08-24 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.antiviral.2021.105167 Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target. García-Dorival I, Cuesta-Geijo MÁ, Barrado-Gil L, Galindo I, Garaigorta U, Urquiza J, Puerto AD, Campillo NE, Martínez A, Gastaminza P, Gil C, Alonso C. Antiviral Res. 2021; 194
Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19.
De Toma I, Dierssen M.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-81451-w
SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.
2021-01-21 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-81451-w Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19. De Toma I, Dierssen M. Sci Rep. 2021; 11 (1)
SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19.
Arce VM, Costoya JA.
Cell Mol Immunol. 2021; 18 (3)
DOI: 10.1038/s41423-020-00616-1
2021-01-14 2021 other brief-report; Journal Article 10.1038/s41423-020-00616-1 SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19. Arce VM, Costoya JA. Cell Mol Immunol. 2021; 18 (3)
SARS-CoV-2 could be spread through hospital medication dispensed to patients: A prospective observational study.
Grau S, Ferrández O, Echeverría-Esnal D, Maldonado R, [...], Padilla E.
Medicine (Baltimore). 2021; 100 (45)
DOI: 10.1097/md.0000000000027592

Abstract

Our objective was to analyze in vitro the persistence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the packaging material of the drugs dispensed to hospital wards. Additionally, to evaluate if the protection with a double plastic bag prevents the contamination of the medication dispensed to an intensive care unit (ICU).On the first part, different materials containing different drugs within an ICU were sampled to confirm the lack of contamination by SARS-CoV-2. The confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. As a control group, in the microbiology laboratory we inoculated the virus into the different surfaces containing the same drugs included in the first part. Samples were obtained with a sterile swab at 3, 6, 8, 10, 14, 21, and 30 days after inoculation and analyzed through real time reverse transcription polymerase chain reaction.None of the studied materials containing the drugs within an ICU was contaminated by SARS-CoV-2. In the second part, SARS-CoV-2 was found in all surfaces for up to 30 days.The use of double-bag unit-dose system to deliver medication in a pandemic seems effective to prevent the potential transmission of SARS-CoV-2. A striking SARS-CoV-2 RNA stability of up to 30 days was found in the surfaces containing the drugs.
2021-11-01 2021 other research-article; Journal Article; Observational Study abstract-available 10.1097/md.0000000000027592 SARS-CoV-2 could be spread through hospital medication dispensed to patients: A prospective observational study. Grau S, Ferrández O, Echeverría-Esnal D, Maldonado R, Puig B, Ramirez A, Canal M, Montero A, González C, Herranz M, Masclans JR, Horcajada JP, Padilla E. Medicine (Baltimore). 2021; 100 (45)
Detection of SARS-CoV-2 RNA in Urine by RT-LAMP: A Very Rare Finding.
García-Bernalt Diego J, Fernández-Soto P, Muñoz-Bellido JL, Febrer-Sendra B, [...], Muro A.
J Clin Med. 2021; 11 (1)
DOI: 10.3390/jcm11010158
Detection of SARS-CoV-2 is routinely performed in naso/oropharyngeal swabs samples from patients via RT-qPCR. The RT-LAMP technology has also been used for viral RNA detection in respiratory specimens with both high sensitivity and specificity. Recently, we developed a novel RT-LAMP test for SARS-CoV-2 RNA detection in nasopharyngeal swab specimens (named, N15-RT-LAMP) that can be performed as a single-tube colorimetric method, in a real-time platform, and as dry-LAMP. To date, there has been very little success in detecting SARS-CoV-2 RNA in urine by RT-qPCR, and the information regarding urine viral excretion is still scarce and not comprehensive. Here, we tested our N15-RT-LAMP on the urine of 300 patients admitted to the Hospital of Salamanca, Spain with clinical suspicion of COVID-19, who had a nasopharyngeal swab RT-qPCR-positive (n = 100), negative (n = 100), and positive with disease recovery (n = 100) result. The positive group was also tested by RT-qPCR for comparison to N15-RT-LAMP. Only a 4% positivity rate was found in the positive group via colorimetric N15-RT-LAMP and 2% via RT-qPCR. Our results are consistent with those obtained in other studies that the presence of SARS-CoV-2 RNA in urine is a very rare finding. The absence of SARS-CoV-2 RNA in urine in the recovered patients might suggest that the urinary route is very rarely used for viral particle clearance.
2021-12-29 2021 other research-article; Journal Article abstract-available 10.3390/jcm11010158 Detection of SARS-CoV-2 RNA in Urine by RT-LAMP: A Very Rare Finding. García-Bernalt Diego J, Fernández-Soto P, Muñoz-Bellido JL, Febrer-Sendra B, Crego-Vicente B, Carbonell C, López-Bernús A, Marcos M, Belhassen-García M, Muro A. J Clin Med. 2021; 11 (1)
Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice.
Vidal E, López-Figueroa C, Rodon J, Pérez M, [...], Segalés J.
Vet Pathol. 2021;
DOI: 10.1177/03009858211066841
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
2021-12-27 2021 other Journal Article abstract-available 10.1177/03009858211066841 Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice. Vidal E, López-Figueroa C, Rodon J, Pérez M, Brustolin M, Cantero G, Guallar V, Izquierdo-Useros N, Carrillo J, Blanco J, Clotet B, Vergara-Alert J, Segalés J. Vet Pathol. 2021;
Severe Epistaxis after Tissue Plasminogen Activator administration for Acute Ischemic Stroke in SARS-COV-2 Infection.
Khandelwal P, Martínez-Pías E, Bach I, Prakash T, [...], Arenillas JF.
Brain Circ. 2021; 7 (2)
DOI: 10.4103/bc.bc_17_21
Patients with COVID-19 may suffer from hemorrhagic complications. Our article highlights two cases of COVID-19-infected patients, who suffered severe epistaxis after initiation of intravenous recombinant tissue plasminogen activator (IV-rtPA) for acute ischemic stroke, followed by a sudden decline in their clinical status and ultimately leading to death within days. Given the global impact and mortality of COVID-19, it is essential to be aware of its unusual presentation and improve therapeutic strategies. We present two cases of individuals who suffered from a large vessel occlusion of and were candidates for both IV-rtPA and mechanical thrombectomy. They received IV-rtPA but had epistaxis so severe that they were not able to receive MT and died within the next few days. There are many potential mechanisms by which epistaxis can happen in an individual with COVID-19 who received IV-rtPA including invasion of the nasal mucosa and endothelium through angiotensin-converting enzyme 2 receptors by the virus. We also hypothesize that the coagulation abnormality seen in COVID-19 patients can be potentiated by the use of treatments such as IV-rtPA. We review these issues with a diagram illustrating the possible mechanisms.
2021-04-01 2021 other Case Reports; case-report abstract-available 10.4103/bc.bc_17_21 Severe Epistaxis after Tissue Plasminogen Activator administration for Acute Ischemic Stroke in SARS-COV-2 Infection. Khandelwal P, Martínez-Pías E, Bach I, Prakash T, Hillen ME, Martínez-Galdámez M, Arenillas JF. Brain Circ. 2021; 7 (2)
Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination.
Almendro-Vázquez P, Laguna-Goya R, Ruiz-Ruigomez M, Utrero-Rico A, [...], Paz-Artal E.
PLoS Pathog. 2021; 17 (12)
DOI: 10.1371/journal.ppat.1010211
The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.
2021-12-28 2021 fondo-covid research-article; Journal Article abstract-available 10.1371/journal.ppat.1010211 Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination. Almendro-Vázquez P, Laguna-Goya R, Ruiz-Ruigomez M, Utrero-Rico A, Lalueza A, Maestro de la Calle G, Delgado P, Perez-Ordoño L, Muro E, Vila J, Zamarron I, Moreno-Batanero M, Chivite-Lacaba M, Gil-Etayo FJ, Martín-Higuera C, Meléndez-Carmona MÁ, Lumbreras C, Arellano I, Alarcon B, Allende LM, Aguado JM, Paz-Artal E. PLoS Pathog. 2021; 17 (12)
Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials.
Han YJ, Lee KH, Yoon S, Nam SW, [...], Shin JI.
Theranostics. 2021; 11 (3)
DOI: 10.7150/thno.48342
Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
2021-01-01 2021 other Systematic Review; review-article; Journal Article abstract-available 10.7150/thno.48342 Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of <i>in vitro</i>, <i>in vivo</i>, and clinical trials. Han YJ, Lee KH, Yoon S, Nam SW, Ryu S, Seong D, Kim JS, Lee JY, Yang JW, Lee J, Koyanagi A, Hong SH, Dragioti E, Radua J, Smith L, Oh H, Ghayda RA, Kronbichler A, Effenberger M, Kresse D, Denicolò S, Kang W, Jacob L, Shin H, Shin JI. Theranostics. 2021; 11 (3)
IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection.
Pérez A, Torregrosa I, D'Marco L, Juan I, [...], Gorriz JL.
Viruses. 2021; 13 (4)
DOI: 10.3390/v13040587
The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgA-DIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN.
2021-03-31 2021 other Case Reports; case-report abstract-available 10.3390/v13040587 IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection. Pérez A, Torregrosa I, D'Marco L, Juan I, Terradez L, Solís MÁ, Moncho F, Carda-Batalla C, Forner MJ, Gorriz JL. Viruses. 2021; 13 (4)
Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon.
Mayneris-Perxachs J, Moreno-Navarrete JM, Ballanti M, Monteleone G, [...], Fernández-Real JM.
Comput Struct Biotechnol J. 2021; 19
DOI: 10.1016/j.csbj.2021.11.007
Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.
2021-11-08 2021 other research-article; Journal Article abstract-available 10.1016/j.csbj.2021.11.007 Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon. Mayneris-Perxachs J, Moreno-Navarrete JM, Ballanti M, Monteleone G, Alessandro Paoluzi O, Mingrone G, Lefebvre P, Staels B, Federici M, Puig J, Garre J, Ramos R, Fernández-Real JM. Comput Struct Biotechnol J. 2021; 19
SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral.
Jimenez-Aleman GH, Castro V, Londaitsbehere A, Gutierrez-Rodríguez M, [...], Gastaminza P.
Pharmaceuticals (Basel). 2021; 14 (10)
DOI: 10.3390/ph14101048
SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.
2021-10-15 2021 other research-article; Journal Article abstract-available 10.3390/ph14101048 SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral. Jimenez-Aleman GH, Castro V, Londaitsbehere A, Gutierrez-Rodríguez M, Garaigorta U, Solano R, Gastaminza P. Pharmaceuticals (Basel). 2021; 14 (10)
Polyphenols and their potential role to fight viral diseases: An overview.
Montenegro-Landívar MF, Tapia-Quirós P, Vecino X, Reig M, [...], Saurina J.
Sci Total Environ. 2021; 801
DOI: 10.1016/j.scitotenv.2021.149719
Fruits, vegetables, spices, and herbs are a potential source of phenolic acids and polyphenols. These compounds are known as natural by-products or secondary metabolites of plants, which are present in the daily diet and provide important benefits to the human body such as antioxidant, anti-inflammatory, anticancer, anti-allergic, antihypertensive and antiviral properties, among others. Plentiful evidence has been provided on the great potential of polyphenols against different viruses that cause widespread health problems. As a result, this review focuses on the potential antiviral properties of some polyphenols and their action mechanism against various types of viruses such as coronaviruses, influenza, herpes simplex, dengue fever, and rotavirus, among others. Also, it is important to highlight the relationship between antiviral and antioxidant activities that can contribute to the protection of cells and tissues of the human body. The wide variety of action mechanisms of antiviral agents, such as polyphenols, against viral infections could be applied as a treatment or prevention strategy; but at the same time, antiviral polyphenols could be used to produce natural antiviral drugs. A recent example of an antiviral polyphenol application deals with the use of hesperidin extracted from Citrus sinensis. The action mechanism of hesperidin relies on its binding to the key entry or spike protein of SARS-CoV-2. Finally, the extraction, purification and recovery of polyphenols with potential antiviral activity, which are essential for virus replication and infection without side-effects, have been critically reviewed.
2021-08-19 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.scitotenv.2021.149719 Polyphenols and their potential role to fight viral diseases: An overview. Montenegro-Landívar MF, Tapia-Quirós P, Vecino X, Reig M, Valderrama C, Granados M, Cortina JL, Saurina J. Sci Total Environ. 2021; 801
Effectiveness of non-invasive ventilation in intensive care unit admitted patients due to SARS-CoV-2 pneumonia.
Belenguer Muncharaz A, Hernández-Garcés H, López-Chicote C, Ribes-García S, [...], Zaragoza-Crespo R.
Med Intensiva (Engl Ed). 2021; 45 (9)
DOI: 10.1016/j.medine.2021.10.008
2021-10-26 2021 other Case Reports; case-report 10.1016/j.medine.2021.10.008 Effectiveness of non-invasive ventilation in intensive care unit admitted patients due to SARS-CoV-2 pneumonia. Belenguer Muncharaz A, Hernández-Garcés H, López-Chicote C, Ribes-García S, Ochagavía-Barbarín J, Zaragoza-Crespo R. Med Intensiva (Engl Ed). 2021; 45 (9)
Anti-ACTH Antibodies in Critically Ill Covid-19 Patients: A Potential Immune Evasion Mechanism of SARS-CoV-2.
Pérez-Torres D, Díaz-Rodríguez C, Armentia-Medina A.
Med Intensiva. 2021;
DOI: 10.1016/j.medin.2021.09.002
2021-10-08 2021 other Case Reports; case-report 10.1016/j.medin.2021.09.002 Anti-ACTH Antibodies in Critically Ill Covid-19 Patients: A Potential Immune Evasion Mechanism of SARS-CoV-2. Pérez-Torres D, Díaz-Rodríguez C, Armentia-Medina A. Med Intensiva. 2021;
SARS-CoV-2 outbreak impact on a trauma unit.
Mills S, Ibarzábal-Gil A, Martínez-Diez JM, Pallarés-Sanmartín J, [...], Rodríguez-Merchán EC.
World J Orthop. 2021; 12 (10)
DOI: 10.5312/wjo.v12.i10.751

Background

From February 2020 onwards, our country has been hit by the coronavirus severe acute respiratory syndrome-2 (SARS-CoV-2) infection. At a glance, hospitals became overrun and had to reformulate all the assistance guidelines, focusing on the coronavirus disease 2019. One year after the start of the pandemic, we present the results of a morbimortality study.

Aim

To analyze how our department was affected by the outbreak in terms of morbimortality, and to analyze demographic data, admission to hospital-related data, and subgroups analyses for patients with hip fractures and polytrauma.

Methods

We designed a study comparing data from patients who were admitted to our unit due to a lower limb fracture or a high energy trauma during the pandemic (from March to April 2020) to those admitted during the same period in 2019 before the pandemic. during the pandemic situation. Both cohorts completed a minimum of 6 mo of follow-up.

Results

The number of patients admitted to hospital in 2020 was nearly half of those in 2019. Hip fractures in the elderly represented 52 out of 73 of the admitted patients. Twenty patients had a positive test result for SARS-CoV-2 infection. Patients with SARS-CoV-2 infection were admitted to the hospital for a longer time than the non-infected (P < 0.001), and had a higher mortality rate during hospitalization and follow-up (P = 0.02). Patients with a hip fracture associated with a severe respiratory syndrome were mostly selected for conservative treatment (P = 0.03).

Conclusion

Mortality and readmission rates were higher in the 2020 cohort and during follow-up, in comparison with the cohort in 2019.
2021-10-18 2021 other research-article; Journal Article abstract-available 10.5312/wjo.v12.i10.751 SARS-CoV-2 outbreak impact on a trauma unit. Mills S, Ibarzábal-Gil A, Martínez-Diez JM, Pallarés-Sanmartín J, Kalbakdij-Sánchez C, Rubio-Suárez JC, Losantos-García I, Rodríguez-Merchán EC. World J Orthop. 2021; 12 (10)
Acute transverse myelitis following SARS-CoV-2 infection.
Jauregui-Larrañaga C, Ostolaza-Ibáñez A, Martín-Bujanda M.
Neurologia (Engl Ed). 2021; 36 (7)
DOI: 10.1016/j.nrleng.2021.05.003
2021-07-22 2021 other Letter 10.1016/j.nrleng.2021.05.003 Acute transverse myelitis following SARS-CoV-2 infection. Jauregui-Larrañaga C, Ostolaza-Ibáñez A, Martín-Bujanda M. Neurologia (Engl Ed). 2021; 36 (7)
Emerging SARS-CoV-2 Variants and Impact in Global Vaccination Programs against SARS-CoV-2/COVID-19.
Gómez CE, Perdiguero B, Esteban M.
Vaccines (Basel). 2021; 9 (3)
DOI: 10.3390/vaccines9030243
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants in different continents is causing a major concern in human global health. These variants have in common a higher transmissibility, becoming dominant within populations in a short time, and an accumulation of a high number of mutations in the spike (S) protein, especially within the amino terminal domain (NTD) and the receptor binding domain (RBD). These mutations have direct implications on virus infection rates through higher affinity of S RBD for the cellular angiotensin-converting enzyme-2 (ACE-2) receptor. There are also signs of enhanced virulence, re-infection frequency, and increased resistance to the action of monoclonal and polyclonal antibodies from convalescence sera and in vaccinated individuals in regions where the variants spread dominantly. In this review, we describe the different SARS-CoV-2 variants that have thus far been identified in various parts of the world with mutational changes and biological properties as well as their impact in medical countermeasures and human health.
2021-03-11 2021 other review-article; Review; Journal Article abstract-available 10.3390/vaccines9030243 Emerging SARS-CoV-2 Variants and Impact in Global Vaccination Programs against SARS-CoV-2/COVID-19. Gómez CE, Perdiguero B, Esteban M. Vaccines (Basel). 2021; 9 (3)
The structural basis of accelerated host cell entry by SARS-CoV-2†.
Seyran M, Takayama K, Uversky VN, Lundstrom K, [...], Uhal BD.
FEBS J. 2021; 288 (17)
DOI: 10.1111/febs.15651
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral 'surfing' of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2.
2020-12-14 2020 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1111/febs.15651 The structural basis of accelerated host cell entry by SARS-CoV-2†. Seyran M, Takayama K, Uversky VN, Lundstrom K, Palù G, Sherchan SP, Attrish D, Rezaei N, Aljabali AAA, Ghosh S, Pizzol D, Chauhan G, Adadi P, Mohamed Abd El-Aziz T, Soares AG, Kandimalla R, Tambuwala M, Hassan SS, Azad GK, Pal Choudhury P, Baetas-da-Cruz W, Serrano-Aroca Á, Brufsky AM, Uhal BD. FEBS J. 2021; 288 (17)
Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)A, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)B, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)D, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)E, Österreichische Gesellschaft für Pneumologie (ÖGP)F in co-operation with the German, Austrian, and Swiss ARIA groupsG, and the European Academy of Allergy and Clinical Immunology (EAACI)H.
Klimek L, Pfaar O, Worm M, Eiwegger T, [...], Jutel M.
Allergol Select. 2020; 4
DOI: 10.5414/alx02166e

Background

Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials and methods

A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results

In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion

The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
2020-09-07 2020 other research-article; Journal Article abstract-available 10.5414/alx02166e Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)<sup>A</sup>, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)<sup>B</sup>, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)<sup>C</sup>, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)<sup>D</sup>, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)<sup>E</sup>, Österreichische Gesellschaft für Pneumologie (ÖGP)<sup>F</sup> in co-operation with the German, Austrian, and Swiss ARIA groups<sup>G</sup>, and the European Academy of Allergy and Clinical Immunology (EAACI)<sup>H</sup>. Klimek L, Pfaar O, Worm M, Eiwegger T, Hagemann J, Ollert M, Untersmayr E, Hoffmann-Sommergruber K, Vultaggio A, Agache I, Bavbek S, Bossios A, Casper I, Chan S, Chatzipetrou A, Vogelberg C, Firinu D, Kauppi P, Kolios A, Kothari A, Matucci A, Palomares O, Szépfalusi Z, Pohl W, Hötzenecker W, Rosenkranz AR, Bergmann KC, Bieber T, Buhl R, Buters J, Darsow U, Keil T, Kleine-Tebbe J, Lau S, Maurer M, Merk H, Mösges R, Saloga J, Staubach P, Jappe U, Rabe KF, Rabe U, Vogelmeier C, Biedermann T, Jung K, Schlenter W, Ring J, Chaker A, Wehrmann W, Becker S, Freudelsperger L, Mülleneisen N, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Tomazic PV, Aberer W, Fink-Wagner AH, Horak F, Wöhrl S, Niederberger-Leppin V, Pali-Schöll I, Pohl W, Roller-Wirnsberger R, Spranger O, Valenta R, Akdis M, Matricardi PM, Spertini F, Khaltaev N, Michel JP, Nicod L, Schmid-Grendelmeier P, Idzko M, Hamelmann E, Jakob T, Werfel T, Wagenmann M, Taube C, Jensen-Jarolim E, Korn S, Hentges F, Schwarze J, O Mahony L, Knol EF, Del Giacco S, Chivato Pérez T, Bousquet J, Bedbrook A, Zuberbier T, Akdis C, Jutel M. Allergol Select. 2020; 4
COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.
Maldonado MD, Romero-Aibar J, Pérez-San-Gregorio MA.
Epidemiol Infect. 2021; 149
DOI: 10.1017/s0950268821001333
The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.
2021-06-16 2021 other Research Support, Non-U.S. Gov't; review-article; Journal Article; Case Reports abstract-available 10.1017/s0950268821001333 COVID-19 pandemic as a risk factor for the reactivation of herpes viruses. Maldonado MD, Romero-Aibar J, Pérez-San-Gregorio MA. Epidemiol Infect. 2021; 149
Impact of Systemic Corticosteroids on Mortality in Older Adults With Critical COVID-19 Pneumonia.
Piniella-Ruiz E, Bellver-Álvarez MT, Mestre-Gómez B, Escolano-Fernández B, [...], Torres-Macho J.
J Gerontol A Biol Sci Med Sci. 2021; 76 (8)
DOI: 10.1093/gerona/glab074

Background

The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In severe acute respiratory syndrome coronavirus 2 infection, the host immune response is thought to play a key role in the pathophysiological effects of lung damage. Therefore, corticosteroid therapy could modulate inflammation-mediated pulmonary injury and thereby reduce progression to severe respiratory failure and death. The aim of this study was to analyze the safety and clinical efficacy of corticosteroid therapy in older adults with severe COVID-19 pneumonia.

Method

We reviewed the clinical records of confirmed COVID-19 patients aged 75 years or older admitted to our hospital over a 3-month period (March 1-May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization guidance on COVID-19, our hospital protocol added corticosteroid for COVID-19 treatment. We compared in-hospital mortality among patients with critical COVID-19 who received corticosteroids therapy and those who did not.

Results

In total, 88 patients (61.5%) were treated with corticosteroids, and 55 patients (38.4%) were not. Both groups were similar in baseline characteristics. The median age was 85 years (interquartile range: 82-89), and 61.5% (88/143) were male. In-hospital mortality was lower in the corticosteroid group (68.2%) compared with patients in the noncorticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (hazard ratio: 0.61; 95% CI: 0.41-0.93; p = .006).

Conclusions

In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.
2021-07-01 2021 other brief-report; Journal Article abstract-available 10.1093/gerona/glab074 Impact of Systemic Corticosteroids on Mortality in Older Adults With Critical COVID-19 Pneumonia. Piniella-Ruiz E, Bellver-Álvarez MT, Mestre-Gómez B, Escolano-Fernández B, Vinat-Prado S, Cabezas-Olea R, Acedo-Gutiérrez MS, Akasbi-Montalvo M, Ryan-Murua P, Bustamante-Fermosel A, Muñoz-Rivas N, Santamaría-García C, Pardo-Guimerá V, Ulla-Anés M, Franco-Moreno A, Torres-Macho J. J Gerontol A Biol Sci Med Sci. 2021; 76 (8)
The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil, November 2019.
Fongaro G, Stoco PH, Souza DSM, Grisard EC, [...], Rodríguez-Lázaro D.
Sci Total Environ. 2021; 778
DOI: 10.1016/j.scitotenv.2021.146198
Human sewage from Florianopolis (Santa Catarina, Brazil) was analyzed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) from October 2019 until March 2020. Twenty five ml of sewage samples were clarified and viruses concentrated using a glycine buffer method coupled with polyethylene glycol precipitation, and viral RNA extracted using a commercial kit. SARS-CoV-2 RNA was detected by RT-qPCR using oligonucleotides targeting N1, S and two RdRp regions. The results of all positive samples were further confirmed by a different RT-qPCR system in an independent laboratory. S and RdRp amplicons were sequenced to confirm identity with SARS-CoV-2. Genome sequencing was performed using two strategies; a sequence-independent single-primer amplification (SISPA) approach, and by direct metagenomics using Illumina's NGS. SARS-CoV-2 RNA was detected on 27th November 2019 (5.49 ± 0.02 log10 SARS-CoV-2 genome copies (GC) L-1), detection being confirmed by an independent laboratory and genome sequencing analysis. The samples in the subsequent three events were positive by all RT-qPCR assays; these positive results were also confirmed by an independent laboratory. The average load was 5.83 ± 0.12 log10 SARS-CoV-2 GC L-1, ranging from 5.49 ± 0.02 log10 GC L-1 (27th November 2019) to 6.68 ± 0.02 log10 GC L-1 (4th March 2020). Our findings demonstrate that SARS-CoV-2 was likely circulating undetected in the community in Brazil since November 2019, earlier than the first reported case in the Americas (21st January 2020).
2021-03-08 2021 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2021.146198 The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil, November 2019. Fongaro G, Stoco PH, Souza DSM, Grisard EC, Magri ME, Rogovski P, Schörner MA, Barazzetti FH, Christoff AP, de Oliveira LFV, Bazzo ML, Wagner G, Hernández M, Rodríguez-Lázaro D. Sci Total Environ. 2021; 778
SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus.
Muñoz-Basagoiti J, Perez-Zsolt D, Carrillo J, Blanco J, [...], Izquierdo-Useros N.
Membranes (Basel). 2021; 11 (1)
DOI: 10.3390/membranes11010064
Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.
2021-01-18 2021 other review-article; Review; Journal Article abstract-available 10.3390/membranes11010064 SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Muñoz-Basagoiti J, Perez-Zsolt D, Carrillo J, Blanco J, Clotet B, Izquierdo-Useros N. Membranes (Basel). 2021; 11 (1)
Host-dependent editing of SARS-CoV-2 in COVID-19 patients.
Gregori J, Cortese MF, Piñana M, Campos C, [...], Quer J.
Emerg Microbes Infect. 2021; 10 (1)
DOI: 10.1080/22221751.2021.1969868
A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1080/22221751.2021.1969868 Host-dependent editing of SARS-CoV-2 in COVID-19 patients. Gregori J, Cortese MF, Piñana M, Campos C, Garcia-Cehic D, Andrés C, Abril JF, Codina MG, Rando A, Esperalba J, Sulleiro E, Joseph J, Saubí N, Colomer-Castell S, Martin MC, Castillo C, Esteban JI, Pumarola T, Rodriguez-Frias F, Antón A, Quer J. Emerg Microbes Infect. 2021; 10 (1)
Coronavirus and other airborne agents with pandemic potential.
Fernandez-Montero JV, Soriano V, Barreiro P, de Mendoza C, [...], Artacho MÁ.
Curr Opin Environ Sci Health. 2020; 17
DOI: 10.1016/j.coesh.2020.09.001
The recent emergence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2) has caused a pandemic, which is the most severe infectious disease outbreak in many decades. Other infective agents such as influenza as well as other neglected viruses such as Lassa virus, Nipah virus or poxviruses are also a cause for concern owing to their attack rate and potential for global spread. Drug-resistant bacteria, such as Mycobacterium tuberculosis, are already a significant public health issue in many countries, and it is expected that they will be expanding in the near future. Finally, airborne bioterrorism agents have high morbidity and mortality rates and should be looked with concern in the current international unrest.
2020-09-24 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.coesh.2020.09.001 Coronavirus and other airborne agents with pandemic potential. Fernandez-Montero JV, Soriano V, Barreiro P, de Mendoza C, Artacho MÁ. Curr Opin Environ Sci Health. 2020; 17
SARS-CoV-2, a Threat to Marine Mammals? A Study from Italian Seawaters.
Audino T, Grattarola C, Centelleghe C, Peletto S, [...], Casalone C.
Animals (Basel). 2021; 11 (6)
DOI: 10.3390/ani11061663
Zoonotically transmitted coronaviruses were responsible for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing the dramatic Coronavirus Disease-2019 (CoViD-19) pandemic, which affected public health, the economy, and society on a global scale. The impact of the SARS-CoV-2 pandemic permeated into our environment and wildlife as well; in particular, concern has been raised about the viral occurrence and persistence in aquatic and marine ecosystems. The discharge of untreated wastewaters carrying infectious SARS-CoV-2 into natural water systems that are home to sea mammals may have dramatic consequences on vulnerable species. The efficient transmission of coronaviruses raises questions regarding the contributions of virus-receptor interactions. The main receptor of SARS-CoV-2 is Angiotensin Converting Enzyme-2 (ACE-2), serving as a functional receptor for the viral spike (S) protein. This study aimed, through the comparative analysis of the ACE-2 receptor with the human one, at assessing susceptibility to SARS-CoV-2 for different species of marine mammals living in Italian waters. We also determined, by means of immunohistochemistry, ACE-2 receptor localization in the lung tissue from different cetacean species, in order to provide a preliminary characterization of ACE-2 expression in the marine mammal respiratory tracts. Furthermore, to evaluate if and how Italian wastewater management and coastal exposition to extreme weather events may led to susceptible marine mammal populations being exposed to SARS-CoV-2, geomapping data were carried out and overlapped. The results showed the potential SARS-CoV-2 exposure for marine mammals inhabiting Italian coastal waters, putting them at risk when swimming and feeding in specific risk areas. Thus, we highlighted the potential hazard of the reverse zoonotic transmission of SARS-CoV-2 infection, along with its impact on marine mammals regularly inhabiting the Mediterranean Sea, while also stressing the need for appropriate action in order to prevent further damage to specific vulnerable populations.
2021-06-03 2021 other research-article; Journal Article abstract-available 10.3390/ani11061663 SARS-CoV-2, a Threat to Marine Mammals? A Study from Italian Seawaters. Audino T, Grattarola C, Centelleghe C, Peletto S, Giorda F, Florio CL, Caramelli M, Bozzetta E, Mazzariol S, Di Guardo G, Lauriano G, Casalone C. Animals (Basel). 2021; 11 (6)
Long-term impact of COVID-19 associated acute respiratory distress syndrome.
Aranda J, Oriol I, Martín M, Feria L, [...], Carratalà J.
J Infect. 2021; 83 (5)
DOI: 10.1016/j.jinf.2021.08.018

Objectives

To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis.

Methods

All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied.

Results

Of 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score.

Conclusion

COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.
2021-08-13 2021 other research-article; Journal Article abstract-available 10.1016/j.jinf.2021.08.018 Long-term impact of COVID-19 associated acute respiratory distress syndrome. Aranda J, Oriol I, Martín M, Feria L, Vázquez N, Rhyman N, Vall-Llosera E, Pallarés N, Coloma A, Pestaña M, Loureiro J, Güell E, Borjabad B, León E, Franz E, Domènech A, Pintado S, Contra A, Cortés MDS, Chivite I, Clivillé R, Vacas M, Ceresuela LM, Carratalà J. J Infect. 2021; 83 (5)
Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19.
Steardo L, Steardo L, Zorec R, Verkhratsky A.
Acta Physiol (Oxf). 2020; 229 (3)
DOI: 10.1111/apha.13473
2020-04-11 2020 other research-article; Review; Journal Article 10.1111/apha.13473 Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Steardo L, Steardo L, Zorec R, Verkhratsky A. Acta Physiol (Oxf). 2020; 229 (3)
Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?
Castro P, Palomo M, Moreno-Castaño AB, Fernández S, [...], Diaz-Ricart M.
Cardiovasc Drugs Ther. 2021;
DOI: 10.1007/s10557-021-07207-w
Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death. Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (PASC) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating. Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved. The clinical manifestations of the COVID-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition. The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus. Cytokine release syndrome can also drive endothelial damage independently. Consequently, a distinctive feature of SARS-CoV-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage. Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe COVID-19 complications. Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity. In addition, the endothelium could represent a very attractive target to both prevent and treat these complications. To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified. In this review, the clinical features of COVID-19, the central role of the endothelium in COVID-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in COVID-19 patients are addressed.
2021-06-07 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10557-021-07207-w Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications? Castro P, Palomo M, Moreno-Castaño AB, Fernández S, Torramadé-Moix S, Pascual G, Martinez-Sanchez J, Richardson E, Téllez A, Nicolas JM, Carreras E, Richardson PG, Badimon JJ, Escolar G, Diaz-Ricart M. Cardiovasc Drugs Ther. 2021;
Psychological Impact of the COVID-19 Pandemic on Out-of-Hospital Health Professionals: A Living Systematic Review.
Soto-Cámara R, García-Santa-Basilia N, Onrubia-Baticón H, Cárdaba-García RM, [...], Navalpotro-Pascual S.
J Clin Med. 2021; 10 (23)
DOI: 10.3390/jcm10235578
Health professionals (HPs), especially those working in the front line, have been one of the groups most affected by the COVID-19 pandemic. The objective of this study is to identify the best available scientific evidence on the impact of the COVID-19 pandemic on the mental health of out-of-hospital HPs in terms of stress, anxiety, depression, and self-efficacy. A living systematic review of the literature was designed, consulting the electronic online versions of the CINHAL, Cochrane Library, Cuiden, IBECS, JBI, LILACS, Medline PyscoDoc, PsycoINFO, Scopus, and Web of Science databases in November 2021. Original research was selected, published in either English, Spanish, French, Italian, or Portuguese. In total, 2082 publications were identified, of which 16 were included in this review. The mental health of out-of-hospital HPs was affected. Being a woman or having direct contact with patients showing suspicious signs of COVID-19 or confirmed cases were the factors related to a greater risk of developing high levels of stress and anxiety; in the case of depressive symptoms, it was having a clinical history of illnesses that could weaken their defenses against infection. Stopping unpleasant emotions and thoughts was the coping strategy most frequently used by these HPs.
2021-11-27 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcm10235578 Psychological Impact of the COVID-19 Pandemic on Out-of-Hospital Health Professionals: A Living Systematic Review. Soto-Cámara R, García-Santa-Basilia N, Onrubia-Baticón H, Cárdaba-García RM, Jiménez-Alegre JJ, Reques-Marugán AM, Molina-Oliva M, Fernández-Domínguez JJ, Matellán-Hernández MP, Morales-Sanchez A, Navalpotro-Pascual S. J Clin Med. 2021; 10 (23)
Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease.
Halpin DMG, Criner GJ, Papi A, Singh D, [...], Vogelmeier CF.
Am J Respir Crit Care Med. 2021; 203 (1)
DOI: 10.1164/rccm.202009-3533so
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.
2021-01-01 2021 other research-article; Review; Journal Article abstract-available 10.1164/rccm.202009-3533so Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Halpin DMG, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, Agusti AA, Vogelmeier CF. Am J Respir Crit Care Med. 2021; 203 (1)
A Year Following the Onset of the COVID-19 Pandemic: Existing Challenges and Ways the Food Industry Has Been Impacted.
Vargas-Ramella M, Lorenzo JM, Bohrer BM, Pateiro M, [...], Franco D.
Foods. 2021; 10 (10)
DOI: 10.3390/foods10102389
The COVID-19 pandemic has created significant impacts for nearly all industrial and societal sectors in the world. As closures and social distancing mandates were implemented to help control the spread of the novel coronavirus designated as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the food industry was immensely affected. This review explores the effects of the COVID-19 pandemic on the food supply chain from a multi-disciplinary viewpoint and provides perspectives on the consequences on food safety and food security, a risk assessment on human-animal interactions, and considers logistical/protocol adjustments required for the food industry. While foodborne transmission of the novel coronavirus SARS-CoV-2 is not a significant factor for food safety as direct transmission of the virus through food products is not evident, food security has been significantly affected by the COVID-19 pandemic. The pandemic threatens food accessibility, especially for vulnerable populations of people, through its effects on food cost and infrastructure, food distribution and public transit access, and social inequities. Currently, global interest for COVID-19 is focused on human health and rightfully so, but adverse effects on the food supply chain are already evident and will likely continue to occur for several years after the pandemic is over, let alone if other global health pandemics of this magnitude surface in upcoming years. Uncertainties over the novel coronavirus have interrupted global trade and supply chains. The pandemic has underlined the importance of a robust and resilient food system, which presents an unprecedented challenge for competent authorities in upcoming years.
2021-10-09 2021 other review-article; Review; Journal Article abstract-available 10.3390/foods10102389 A Year Following the Onset of the COVID-19 Pandemic: Existing Challenges and Ways the Food Industry Has Been Impacted. Vargas-Ramella M, Lorenzo JM, Bohrer BM, Pateiro M, Cantalapiedra JJ, Franco D. Foods. 2021; 10 (10)
Impact of COVID-19 in Liver Disease Progression.
Martinez MA, Franco S.
Hepatol Commun. 2021; 5 (7)
DOI: 10.1002/hep4.1745
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 19 (COVID-19), which has infected millions of people worldwide in only a few months. A minority, but significant number, of infected individuals require hospitalization and intensive care. From the start of this new virus pandemic, it was apparent that obese and/or diabetic individuals had a bad prognosis for COVID-19 progression, strongly suggesting an association between liver disease and severe COVID-19. Because chronic liver disease (CLD) is associated with immune dysregulation and inflammation, it is unsurprising that patients with CLD may carry a greater risk of adverse outcomes following SARS-CoV-2 infection. Initial COVID-19 data have also indicated that healthy infected individuals display abnormal liver function tests, suggesting a possible direct implication of SARS-CoV-2 in liver damage. Here we show that COVID-19 affects the liver metabolism and increases the morbidity and mortality of individuals with underlying CLD.
2021-05-31 2021 other review-article; Review; Journal Article abstract-available 10.1002/hep4.1745 Impact of COVID-19 in Liver Disease Progression. Martinez MA, Franco S. Hepatol Commun. 2021; 5 (7)
Neurological manifestations of COVID-19 in patients: from path physiology to therapy.
Merino JJ, Macho-González A, Benedi J, González MP.
Neurol Sci. 2021; 42 (12)
DOI: 10.1007/s10072-021-05505-7
Coronavirus is a family of ARN positive single-stranded belonging to the family of Coronaviridae. There are several families of coronavirus that transmit more or less serious diseases. However, the so-called coronavirus-19 (SARS-CoV2) is the one that is currently causing most of the problems; in fact, biological dysfunctions that this virus causes provoke damage in various organs, from the lung to the heart, the kidney, the circulatory system, and even the brain. The neurological manifestations caused by viral infection, as well as the hypercoagulopathy and systemic inflammation, have been reported in several studies. In this review, we update the neurological mechanisms by which coronavirus-19 causes neurological manifestation in patients such as encephalomyelitis, Guillain-Barré syndrome, lacunars infarcts, neuropsychiatry disorders such as anxiety and depression, and vascular alterations. This review explains (a) the possible pathways by which coronavirus-19 can induce the different neurological manifestations, (b) the strategies used by the virus to cross the barrier system, (c) how the immune system responds to the infection, and (d) the treatment than can be administered to the COVID-19 patients.
2021-08-21 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10072-021-05505-7 Neurological manifestations of COVID-19 in patients: from path physiology to therapy. Merino JJ, Macho-González A, Benedi J, González MP. Neurol Sci. 2021; 42 (12)
A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework.
Pérez-Moraga R, Forés-Martos J, Suay-García B, Duval JL, [...], Climent J.
Pharmaceutics. 2021; 13 (4)
DOI: 10.3390/pharmaceutics13040488
Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 116 million cases and 2.5 million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date. We applied a novel computational pipeline aimed to accelerate the process of identifying drug repurposing candidates which allows us to compare three-dimensional protein structures. Its use in conjunction with two in silico validation strategies (molecular docking and transcriptomic analyses) allowed us to identify a set of potential drug repurposing candidates targeting three viral proteins (3CL viral protease, NSP15 endoribonuclease, and NSP12 RNA-dependent RNA polymerase), which included rutin, dexamethasone, and vemurafenib. This is the first time that a topological data analysis (TDA)-based strategy has been used to compare a massive number of protein structures with the final objective of performing drug repurposing to treat SARS-CoV-2 infection.
2021-04-02 2021 other research-article; Journal Article abstract-available 10.3390/pharmaceutics13040488 A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework. Pérez-Moraga R, Forés-Martos J, Suay-García B, Duval JL, Falcó A, Climent J. Pharmaceutics. 2021; 13 (4)
Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19.
Bannerman BP, Júlvez J, Oarga A, Blundell TL, [...], Floto RA.
Life Sci Alliance. 2021; 4 (10)
DOI: 10.26508/lsa.202000954
The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.
2021-08-05 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.26508/lsa.202000954 Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19. Bannerman BP, Júlvez J, Oarga A, Blundell TL, Moreno P, Floto RA. Life Sci Alliance. 2021; 4 (10)
Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm.
Lippi G, Sanchis-Gomar F, Henry BM.
Ann Transl Med. 2020; 8 (7)
DOI: 10.21037/atm.2020.03.157
The "novel" coronavirus disease 2019 (abbreviated "COVID-19") is the third coronavirus outbreak emerging during the past two decades. This infectious disease, sustained by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been recently declared a global pandemic by the World Health Organization. Despite the concerning epidemiological burden, many people, including some policymakers, are underestimating this pandemic and are remaining enigmatically inactive against a human pathology which, for a combination of reasons, can be reasonably defined as a perfect storm (i.e., the "wrong virus" at the "wrong time"). These many paradigmatic aspects include SARS-CoV-2 structure and peculiar biology of infection, high risk of inter-human transmission, long incubation time combined with early and sustained viral load, existence of asymptomatic or mildly-symptomatic carriers, viral shedding for days after symptom relief, unfavorable progression towards respiratory distress and death in up to 5-10% of patients thus causing dramatic healthcare challenges, as well as environmental contamination. Last but not least, the combination of the current case fatality rate with the extraordinary number of people that could be potentially infected by SARS-CoV-2 would permit to estimate that the worldwide deaths for COVID-19 may even approximate those recorded during World War II if appropriate restrictive measures for preventing human-to-human transmission are not readily undertaken. Everybody should be inexcusably aware that this is not a drill, and that the consequences of inadequate action will be tragedy.
2020-04-01 2020 other review-article; Review; Journal Article abstract-available 10.21037/atm.2020.03.157 Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Lippi G, Sanchis-Gomar F, Henry BM. Ann Transl Med. 2020; 8 (7)
Human recombinant soluble ACE2 in severe COVID-19.
Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, [...], Penninger JM.
Lancet Respir Med. 2020; 8 (11)
DOI: 10.1016/s2213-2600(20)30418-5
2020-09-24 2020 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report 10.1016/s2213-2600(20)30418-5 Human recombinant soluble ACE2 in severe COVID-19. Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS, Penninger JM. Lancet Respir Med. 2020; 8 (11)
Effect of ramipril on kidney, lung and heart ACE2 in a diabetic mice model.
Vergara A, Jacobs-Cachá C, Molina-Van den Bosch M, Domínguez-Báez P, [...], Soler MJ.
Mol Cell Endocrinol. 2021; 529
DOI: 10.1016/j.mce.2021.111263

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19). The main organ affected in this infection is the lung and the virus uses the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the target cells. In this context, a controversy raised regarding the use of renin-angiotensin system (RAAS) blockers, as these drugs might increase ACE2 expression in some tissues and potentially increase the risk for SARS-CoV-2 infection. This is specially concerning in diabetic patients as diabetes is a risk factor for COVID-19.

Methods

12-week old diabetic mice (db/db) were treated with ramipril, or vehicle control for 8 weeks. Non-diabetic db/m mice were included as controls. ACE2 expression and activity were studied in lung, kidney and heart of these animals.

Results

Kidney ACE2 activity was increased in the db/db mice as compared to the db/m (143.2% ± 23% vs 100% ± 22.3%, p = 0.004), whereas ramipril had no significant effect. In the lung, no differences were found in ACE2 when comparing db/db mice to db/m and ramipril also had no significant effect. In the heart, diabetes decreased ACE2 activity (83% ± 16.8%, vs 100% ± 23.1% p = 0.02), and ramipril increased ACE2 significantly (83% ± 16.8% vs 98.2% ± 15%, p = 0.04).

Conclusions

In a mouse model of type 2 diabetes, ramipril had no significant effect on ACE2 activity in either kidneys or in the lungs. Therefore, it is unlikely that RAAS blockers or at least angiotensin-converting enzyme inhibitors increase the risk of SARS-CoV-2 infection through increasing ACE2.
2021-03-31 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.mce.2021.111263 Effect of ramipril on kidney, lung and heart ACE2 in a diabetic mice model. Vergara A, Jacobs-Cachá C, Molina-Van den Bosch M, Domínguez-Báez P, Benito B, García-Carro C, Serón D, Soler MJ. Mol Cell Endocrinol. 2021; 529
Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy?
Hijona Elósegui JJ, Carballo García AL, Fernández Risquez AC, Bermúdez Quintana M, [...], Expósito Montes JF.
Rev Clin Esp (Barc). 2021; 221 (2)
DOI: 10.1016/j.rceng.2020.06.002

Background and objetive

On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy.

Patients and methods

Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy.

Results

There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid.

Conclusions

It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.
2020-07-10 2020 other brief-report; Journal Article abstract-available 10.1016/j.rceng.2020.06.002 Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy? Hijona Elósegui JJ, Carballo García AL, Fernández Risquez AC, Bermúdez Quintana M, Expósito Montes JF. Rev Clin Esp (Barc). 2021; 221 (2)
A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet?
Macip G, Garcia-Segura P, Mestres-Truyol J, Saldivar-Espinoza B, [...], Garcia-Vallvé S.
Int J Mol Sci. 2021; 23 (1)
DOI: 10.3390/ijms23010259
In this review, we collected 1765 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M-pro inhibitors from the bibliography and other sources, such as the COVID Moonshot project and the ChEMBL database. This set of inhibitors includes only those compounds whose inhibitory capacity, mainly expressed as the half-maximal inhibitory concentration (IC50) value, against M-pro from SARS-CoV-2 has been determined. Several covalent warheads are used to treat covalent and non-covalent inhibitors separately. Chemical space, the variation of the IC50 inhibitory activity when measured by different methods or laboratories, and the influence of 1,4-dithiothreitol (DTT) are discussed. When available, we have collected the values of inhibition of viral replication measured with a cellular antiviral assay and expressed as half maximal effective concentration (EC50) values, and their possible relationship to inhibitory potency against M-pro is analyzed. Finally, the most potent covalent and non-covalent inhibitors that simultaneously inhibit the SARS-CoV-2 M-pro and the virus replication in vitro are discussed.
2021-12-27 2021 other review-article; Review; Journal Article abstract-available 10.3390/ijms23010259 A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet? Macip G, Garcia-Segura P, Mestres-Truyol J, Saldivar-Espinoza B, Pujadas G, Garcia-Vallvé S. Int J Mol Sci. 2021; 23 (1)
Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review.
Caparros-Gonzalez RA, Pérez-Morente MA, Hueso-Montoro C, Álvarez-Serrano MA, [...], de la Torre-Luque A.
Nutrients. 2020; 12 (11)
DOI: 10.3390/nu12113570

Background

There is inconclusive evidence regarding congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. A narrative review was conducted with the aim of guiding clinicians on the management of pregnant women with respect to congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections and breastfeeding during the COVID-19 pandemic.

Methods

Searches were conducted in Web of Science, PubMed, Scopus, Dialnet, CUIDEN, Scielo, and Virtual Health Library to identify observational, case series, case reports, and randomized controlled trial studies assessing the transmission of SARS-CoV-2 from mother to baby and/or through breastfeeding during the COVID-19 pandemic.

Results

A total of 49 studies was included in this review, comprising 329 pregnant women and 331 neonates (two pregnant women delivered twins). The studies were performed in China (n = 26), USA (n = 7), Italy (n = 3), Iran (n = 2), Switzerland (n = 1), Spain (n = 1), Turkey (n = 1), Australia (n = 1), India (n = 1), Germany (n = 1), France (n = 1), Canada (n = 1), Honduras (n = 1), Brazil (n = 1), and Peru (n = 1). Samples from amniotic fluid, umbilical cord blood, placenta, cervical secretion, and breastmilk were collected and analyzed. A total of 15 placental swabs gave positive results for SARS-CoV-2 ribonucleic acid (RNA) on the fetal side of the placenta. SARS-CoV-2 RNA was found in seven breastmilk samples. One umbilical cord sample was positive for SARS-CoV-2. One amniotic fluid sample tested positive for SARS-CoV-2.

Conclusions

This study presents some evidence to support the potential of congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. Mothers should follow recommendations including wearing a facemask and hand washing before and after breastfeeding.
2020-11-20 2020 other review-article; Review; Journal Article abstract-available 10.3390/nu12113570 Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review. Caparros-Gonzalez RA, Pérez-Morente MA, Hueso-Montoro C, Álvarez-Serrano MA, de la Torre-Luque A. Nutrients. 2020; 12 (11)
Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record
Moreno T, Gibbons W.
Geoscience Frontiers. 2021;
DOI:
Graphical abstract Ongoing uncertainty over the relative importance of aerosol transmission of COVID-19 is in part rooted in the history of medical science and our understanding of how epidemic diseases can spread through human populations. Ancient Greek medical theory held that such illnesses are transmitted by airborne pathogenic emanations containing particulate matter (“miasmata”). Notable Roman and medieval scholars such as Varro, Ibn al-Khatib and Fracastoro developed these ideas, combining them with early germ theory and the concept of contagion. A widely held but vaguely defined belief in toxic miasmatic mists as a dominant causative agent in disease propagation was overtaken by the science of 19th century microbiology and epidemiology, especially in the study of cholera, which was proven to be mainly transmitted by contaminated water. Airborne disease transmission came to be viewed as burdened by a dubious historical reputation and difficult to demonstrate convincingly. A breakthrough came with the classic mid-20th century work of Wells, Riley and Mills who proved how expiratory aerosols (their “droplet nuclei”) could transport still-infectious tuberculosis bacteria through ventilation systems. The topic of aerosol transmission of pathogenic respiratory diseases assumed a new dimension with the mid-late 20th century “Great Acceleration” of an increasingly hypermobile human population repeatedly infected by different strains of zoonotic viruses, and has taken centre stage this century in response to outbreaks of new respiratory infections that include coronaviruses. From a geoscience perspective, the consequences of pandemic-status diseases such as COVID-19, produced by viral pathogens utilising aerosols to infect a human population currently approaching 8 billion, are far-reaching and unprecedented. The obvious and sudden impacts on for example waste plastic production, water and air quality and atmospheric chemistry are accelerating human awareness of current environmental challenges. As such, the “anthropause” lockdown enforced by COVID-19 may come to be seen as a harbinger of change great enough to be preserved in the Anthropocene stratal record.
2021-08-11 2021 other research-article; Journal Article abstract-available Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record Moreno T, Gibbons W. Geoscience Frontiers. 2021;
Platinum chloride-based viability RT-qPCR for SARS-CoV-2 detection in complex samples.
Cuevas-Ferrando E, Randazzo W, Pérez-Cataluña A, Falcó I, [...], Sánchez G.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-97700-x
Isolation, contact tracing and restrictions on social movement are being globally implemented to prevent and control onward spread of SARS-CoV-2, even though the infection risk modelled on RNA detection by RT-qPCR remains biased as viral shedding and infectivity are not discerned. Thus, we aimed to develop a rapid viability RT-qPCR procedure to infer SARS-CoV-2 infectivity in clinical specimens and environmental samples. We screened monoazide dyes and platinum compounds as viability molecular markers on five SARS-CoV-2 RNA targets. A platinum chloride-based viability RT-qPCR was then optimized using genomic RNA, and inactivated SARS-CoV-2 particles inoculated in buffer, stool, and urine. Our results were finally validated in nasopharyngeal swabs from persons who tested positive for COVID-19 and in wastewater samples positive for SARS-CoV-2 RNA. We established a rapid viability RT-qPCR that selectively detects potentially infectious SARS-CoV-2 particles in complex matrices. In particular, the confirmed positivity of nasopharyngeal swabs following the viability procedure suggests their potential infectivity, while the complete prevention of amplification in wastewater indicated either non-infectious particles or free RNA. The viability RT-qPCR approach provides a more accurate ascertainment of the infectious viruses detection and it may complement analyses to foster risk-based investigations for the prevention and control of new or re-occurring outbreaks with a broad application spectrum.
2021-09-13 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-97700-x Platinum chloride-based viability RT-qPCR for SARS-CoV-2 detection in complex samples. Cuevas-Ferrando E, Randazzo W, Pérez-Cataluña A, Falcó I, Navarro D, Martin-Latil S, Díaz-Reolid A, Girón-Guzmán I, Allende A, Sánchez G. Sci Rep. 2021; 11 (1)
Positive association between outdoor air pollution and the incidence and severity of COVID-19. A review of the recent scientific evidences.
Marquès M, Domingo JL.
Environ Res. 2022; 203
DOI: 10.1016/j.envres.2021.111930
In June 2020, we published a review focused on assessing the influence of various air pollutants on the transmission of SARS-CoV-2, and the severity of COVID-19 in patients infected by the coronavirus. The results of most of those reviewed studies suggested that chronic exposure to certain air pollutants might lead to more severe and lethal forms of COVID-19, as well as delays/complications in the recovery of the patients. Since then, a notable number of studies on this topic have been published, including also various reviews. Given the importance of this issue, we have updated the information published since our previous review. Taking together the previous results and those of most investigations now reviewed, we have concluded that there is a significant association between chronic exposure to various outdoor air pollutants: PM2.5, PM10, O3, NO2, SO2 and CO, and the incidence/risk of COVID-19 cases, as well as the severity/mortality of the disease. Unfortunately, studies on the potential influence of other important air pollutants such as VOCs, dioxins and furans, or metals, are not available in the scientific literature. In relation to the influence of outdoor air pollutants on the transmission of SARS-CoV-2, although the scientific evidence is much more limited, some studies point to PM2.5 and PM10 as potential airborne transmitters of the virus. Anyhow, it is clear that environmental air pollution plays an important negative role in COVID-19, increasing its incidence and mortality.
2021-08-21 2021 other research-article; Review; Journal Article abstract-available 10.1016/j.envres.2021.111930 Positive association between outdoor air pollution and the incidence and severity of COVID-19. A review of the recent scientific evidences. Marquès M, Domingo JL. Environ Res. 2022; 203
A compendium answering 150 questions on COVID-19 and SARS-CoV-2.
Riggioni C, Comberiati P, Giovannini M, Agache I, [...], Akdis CA.
Allergy. 2020; 75 (10)
DOI: 10.1111/all.14449
In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.
2020-07-20 2020 other review-article; Review; Journal Article abstract-available 10.1111/all.14449 A compendium answering 150 questions on COVID-19 and SARS-CoV-2. Riggioni C, Comberiati P, Giovannini M, Agache I, Akdis M, Alves-Correia M, Antó JM, Arcolaci A, Azkur AK, Azkur D, Beken B, Boccabella C, Bousquet J, Breiteneder H, Carvalho D, De Las Vecillas L, Diamant Z, Eguiluz-Gracia I, Eiwegger T, Eyerich S, Fokkens W, Gao YD, Hannachi F, Johnston SL, Jutel M, Karavelia A, Klimek L, Moya B, Nadeau KC, O'Hehir R, O'Mahony L, Pfaar O, Sanak M, Schwarze J, Sokolowska M, Torres MJ, van de Veen W, van Zelm MC, Wang Y, Zhang L, Jiménez-Saiz R, Akdis CA. Allergy. 2020; 75 (10)
Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram.
Attia ZI, Kapa S, Dugan J, Pereira N, [...], Discover Consortium (Digital and Noninvasive Screening for COVID-19 with AI ECG Repository).
Mayo Clin Proc. 2021; 96 (8)
DOI: 10.1016/j.mayocp.2021.05.027

Objective

To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG).

Methods

A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site.

Results

The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%.

Conclusion

Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control.
2021-08-01 2021 other Research Support, Non-U.S. Gov't; research-article; Multicenter Study; Journal Article abstract-available 10.1016/j.mayocp.2021.05.027 Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram. Attia ZI, Kapa S, Dugan J, Pereira N, Noseworthy PA, Jimenez FL, Cruz J, Carter RE, DeSimone DC, Signorino J, Halamka J, Chennaiah Gari NR, Madathala RS, Platonov PG, Gul F, Janssens SP, Narayan S, Upadhyay GA, Alenghat FJ, Lahiri MK, Dujardin K, Hermel M, Dominic P, Turk-Adawi K, Asaad N, Svensson A, Fernandez-Aviles F, Esakof DD, Bartunek J, Noheria A, Sridhar AR, Lanza GA, Cohoon K, Padmanabhan D, Pardo Gutierrez JA, Sinagra G, Merlo M, Zagari D, Rodriguez Escenaro BD, Pahlajani DB, Loncar G, Vukomanovic V, Jensen HK, Farkouh ME, Luescher TF, Su Ping CL, Peters NS, Friedman PA, Discover Consortium (Digital and Noninvasive Screening for COVID-19 with AI ECG Repository). Mayo Clin Proc. 2021; 96 (8)
The Rheumatology Drugs for COVID-19 Management: Which and When?
Atzeni F, Masala IF, Rodríguez-Carrio J, Ríos-Garcés R, [...], Cervera R.
J Clin Med. 2021; 10 (4)
DOI: 10.3390/jcm10040783

Introduction

While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.
2021-02-16 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcm10040783 The Rheumatology Drugs for COVID-19 Management: Which and When? Atzeni F, Masala IF, Rodríguez-Carrio J, Ríos-Garcés R, Gerratana E, La Corte L, Giallanza M, Nucera V, Riva A, Espinosa G, Cervera R. J Clin Med. 2021; 10 (4)
Impact of COVID-19 at the Ocular Level: A Citation Network Study.
Sánchez-Tena MÁ, Martinez-Perez C, Villa-Collar C, Alvarez-Peregrina C.
J Clin Med. 2021; 10 (7)
DOI: 10.3390/jcm10071340

Background

The main objective of this study was to use citation networks to analyze the relationship between different publications on the impact of COVID-19 at an ocular level and their authors. Furthermore, the different research areas will be identified, and the most cited publication will be determined.

Materials and methods

The publications were searched within the Web of Science database, using "ocular", "SARS-CoV-2", "ophthalmology", "eyesight", and "COVID-19" as keywords for the period between January 2020 and January 2021. The Citation Network Explorer and the CiteSpace software were used to analyze the different publications.

Results

A total of 389 publications with 890 citations generated on the web were found. It must be highlighted that July was the month with the largest number of publications. The most cited ones were "Characteristics of Ocular Findings of Patients with Coronavirus Disease 2019 (COVID-19) in Hubei Province, China" by Wu et al., which was published in May 2020. Three groups covering the different research areas in this field were found using the clustering functions: ocular manifestations, teleophthalmology, and personal protective equipment.

Conclusions

The citation network has shown a comprehensive and objective analysis of the main studies on the impact of COVID-19 in ocular disease.
2021-03-24 2021 other research-article; Journal Article abstract-available 10.3390/jcm10071340 Impact of COVID-19 at the Ocular Level: A Citation Network Study. Sánchez-Tena MÁ, Martinez-Perez C, Villa-Collar C, Alvarez-Peregrina C. J Clin Med. 2021; 10 (7)
Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?
Romero A, Ramos E, López-Muñoz F, Gil-Martín E, [...], Reiter RJ.
Cell Mol Neurobiol. 2020;
DOI: 10.1007/s10571-020-00938-8
The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Although the clinical symptoms mostly have been characterized, the scientific community still doesn´t know how SARS-CoV-2 successfully reaches and spreads throughout the central nervous system (CNS) inducing brain damage. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue. This finding reveals a new direction in the search for a neurotherapeutic strategy in the COVID-19 patients with underlying diseases. Here, we discuss the COVID-19 outbreak in a neuroinvasiveness context and suggest the therapeutic use of high doses of melatonin, which may favorably modulate the immune response and neuroinflammation caused by SARS-CoV-2. However, clinical trials elucidating the efficacy of melatonin in the prevention and clinical management in the COVID-19 patients should be actively encouraged.
2020-08-09 2020 other review-article; Review; Journal Article abstract-available 10.1007/s10571-020-00938-8 Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin? Romero A, Ramos E, López-Muñoz F, Gil-Martín E, Escames G, Reiter RJ. Cell Mol Neurobiol. 2020;
Epidemiological approximation of the enteric manifestation and possible fecal-oral transmission in COVID-19: a preliminary systematic review.
Pamplona J, Solano R, Soler C, Sabat M.
Eur J Gastroenterol Hepatol. 2021; 33 (12)
DOI: 10.1097/meg.0000000000001934
The recent appearance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has led to the publication of the first evidence on gastrointestinal symptoms (GIS), the possible enteric involvement of the virus and the detection of RNA in stool, with its possible implication in the fecal-oral transmission of coronavirus disease 2019 (COVID-19). We aimed to conduct a systematic review to describe the epidemiological scientific evidence on GIS, enteric involvement and fecal excretion of SARS-CoV-2 viral RNA and to discuss the possible fecal-oral transmission pathway of COVID-19.
2021-12-01 2021 other Systematic Review; Journal Article abstract-available 10.1097/meg.0000000000001934 Epidemiological approximation of the enteric manifestation and possible fecal-oral transmission in COVID-19: a preliminary systematic review. Pamplona J, Solano R, Soler C, Sabat M. Eur J Gastroenterol Hepatol. 2021; 33 (12)
Elevated Anti-SARS-CoV-2 Antibodies and IL-6, IL-8, MIP-1β, Early Predictors of Severe COVID-19.
Codina H, Vieitez I, Gutierrez-Valencia A, Skouridou V, [...], Poveda E.
Microorganisms. 2021; 9 (11)
DOI: 10.3390/microorganisms9112259
Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels' decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity.
2021-10-29 2021 fondo-covid research-article; Journal Article abstract-available 10.3390/microorganisms9112259 Elevated Anti-SARS-CoV-2 Antibodies and IL-6, IL-8, MIP-1β, Early Predictors of Severe COVID-19. Codina H, Vieitez I, Gutierrez-Valencia A, Skouridou V, Martínez C, Patiño L, Botero-Gallego M, Trujillo-Rodríguez M, Serna-Gallego A, Muñoz-Muela E, Bobillo MM, Pérez A, Cabrera-Alvar JJ, Crespo M, O'Sullivan CK, Ruiz-Mateos E, Poveda E. Microorganisms. 2021; 9 (11)
Potential of pulsed light technology for control of SARS-CoV-2 in hospital environments.
Jean J, Rodríguez-López MI, Jubinville E, Núñez-Delicado E, [...], Gómez-López VM.
J Photochem Photobiol B. 2021; 215
DOI: 10.1016/j.jphotobiol.2020.112106
The emergence of the SARS-CoV-2 infection and its potential transmission through touching surfaces in clinical environments have impelled the use of conventional and novel methods of disinfection to prevent its spreading. Among the latter, pulsed light may be an effective, non-chemical decontamination alternative. Pulsed light technology inactivates microorganisms and viruses by using high intensity polychromatic light pulses, which degrades nucleic acids and proteins. This review describes this technology, compiles and critically analyzes the evidence about the virucidal efficacy of pulsed light technology with view on its potential use against SARS-CoV-2 in touching surfaces in health-care facilities. The efficacy of pulsed light proved against many different kind of viruses allows to conclude that is a suitable candidate to inactivate SARS-CoV-2 as long as the required fluence is applied and the appropriated exposure to contaminated surfaces is guaranteed.
2020-12-28 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.jphotobiol.2020.112106 Potential of pulsed light technology for control of SARS-CoV-2 in hospital environments. Jean J, Rodríguez-López MI, Jubinville E, Núñez-Delicado E, Gómez-López VM. J Photochem Photobiol B. 2021; 215
Elimination of SARS-CoV-2 along wastewater and sludge treatment processes.
Serra-Compte A, González S, Arnaldos M, Berlendis S, [...], Litrico X.
Water Res. 2021; 202
DOI: 10.1016/j.watres.2021.117435
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is shed in the feces of infected people. As a consequence, genomic RNA of the virus can be detected in wastewater. Although the presence of viral RNA does not inform on the infectivity of the virus, this presence of genetic material raised the question of the effectiveness of treatment processes in reducing the virus in wastewater and sludge. In this work, treatment lines of 16 wastewater treatment plants were monitored to evaluate the removal of SARS-CoV-2 RNA in raw, processed waters and sludge, from March to May 2020. Viral RNA copies were enumerated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in 5 different laboratories. These laboratories participated in proficiency testing scheme and their results demonstrated the reliability and comparability of the results obtained for each one. SARS-CoV-2 RNA was found in 50.5% of the 101 influent wastewater samples characterized. Positive results were detected more frequently in those regions with a COVID-19 incidence higher than 100 cases per 100,000 inhabitants. Wastewater treatment plants (WWTPs) significantly reduced the occurrence of virus RNA along the water treatment lines. Secondary treatment effluents showed an occurrence of SARS-CoV-2 RNA in 23.3% of the samples and no positive results were found after MBR and chlorination. Non-treated sludge (from primary and secondary treatments) presented a higher occurrence of SARS-CoV-2 RNA than the corresponding water samples, demonstrating the affinity of virus particles for solids. Furthermore, SARS-CoV-2 RNA was detected in treated sludge after thickening and anaerobic digestion, whereas viral RNA was completely eliminated from sludge only when thermal hydrolysis was applied. Finally, co-analysis of SARS-CoV-2 and F-specific RNA bacteriophages was done in the same water and sludge samples in order to investigate the potential use of these bacteriophages as indicators of SARS-CoV-2 fate and reduction along the wastewater treatment.
2021-07-15 2021 other research-article; Journal Article abstract-available 10.1016/j.watres.2021.117435 Elimination of SARS-CoV-2 along wastewater and sludge treatment processes. Serra-Compte A, González S, Arnaldos M, Berlendis S, Courtois S, Loret JF, Schlosser O, Yáñez AM, Soria-Soria E, Fittipaldi M, Saucedo G, Pinar-Méndez A, Paraira M, Galofré B, Lema JM, Balboa S, Mauricio-Iglesias M, Bosch A, Pintó RM, Bertrand I, Gantzer C, Montero C, Litrico X. Water Res. 2021; 202
Diabetic Kidney Disease and COVID-19: The Crash of Two Pandemics.
D'Marco L, Puchades MJ, Romero-Parra M, Gorriz JL.
Front Med (Lausanne). 2020; 7
DOI: 10.3389/fmed.2020.00199
2020-05-06 2020 other discussion; Journal Article 10.3389/fmed.2020.00199 Diabetic Kidney Disease and COVID-19: The Crash of Two Pandemics. D'Marco L, Puchades MJ, Romero-Parra M, Gorriz JL. Front Med (Lausanne). 2020; 7
Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern.
Martín-Galiano AJ, Díez-Fuertes F, McConnell MJ, López D.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.732693
The effect of emerging SARS-CoV-2 variants on vaccine efficacy is of critical importance. In this study, the potential impact of mutations that facilitate escape from the cytotoxic cellular immune response in these new virus variants for the 551 most abundant HLA class I alleles was analyzed. Computational prediction showed that most of these alleles, that cover >90% of the population, contain enough epitopes without escape mutations in the principal SARS-CoV-2 variants. These data suggest that the cytotoxic cellular immune protection elicited by vaccination is not greatly affected by emerging SARS-CoV-2 variants.
2021-11-25 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2021.732693 Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern. Martín-Galiano AJ, Díez-Fuertes F, McConnell MJ, López D. Front Immunol. 2021; 12
From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio.
Arkin LM, Moon JJ, Tran JM, Asgari S, [...], COVID Human Genetic Effort.
J Invest Dermatol. 2021; 141 (12)
DOI: 10.1016/j.jid.2021.05.024
Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.
2021-07-15 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.jid.2021.05.024 From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio. Arkin LM, Moon JJ, Tran JM, Asgari S, O'Farrelly C, Casanova JL, Cowen EW, Mays JW, Singh AM, Drolet BA, COVID Human Genetic Effort. J Invest Dermatol. 2021; 141 (12)
The quality of Internet information relating to 2019-nCov transmission control in dental practice.
Camacho-Alonso F, Lacal-Luján J.
J Clin Exp Dent. 2021; 13 (3)
DOI: 10.4317/jced.57573

Background

To date, the quality of the Internet information regarding the control and management of 2019-nCov virus transmission in dental clinics has not been evaluated. The aim of this study was to evaluate the quality of Internet information about the control of 2019-nCov transmission in dental practice.

Material and methods

Internet websites were identified daily using two search engines: Google and Yahoo! during the week from 20-06-2020 to 26-06-2020, applying the search term "2019-nCov transmission control in dental practice." The first 100 consecutive sites identified in each search were visited and classified. The quality of information contained in each website was analyzed using the Journal of the American Medical Association (JAMA) benchmarks, whether the website had been granted the Health on the Net Foundation Code of Conduct (HONcode), and a new tool for evaluating the quality of Internet websites providing information relating to 2019-nCov transmission control in dental practice, which awards a score of 0-40 points (8-13: poor; 14-26: medium; and 27-40 high).

Results

After the exclusion of duplicates, non-functioning websites, books/journals, irrelevant websites, or websites not in English, a total of 30 websites were evaluated. Only 6.66% fulfilled all four JAMA benchmarks, none had been granted the HONcode, and only 10% presented high quality information.

Conclusions

The quality of Internet information about 2019-nCov transmission control in dental practice is poor. This study points to the need to improve the quality of information available on the Internet relating to 2019-nCov transmission control in dental practice. Key words:2019-nCov, COVID-19, transmission control in dental practice, Internet, quality of information.
2021-03-01 2021 other research-article; Journal Article abstract-available 10.4317/jced.57573 The quality of Internet information relating to 2019-nCov transmission control in dental practice. Camacho-Alonso F, Lacal-Luján J. J Clin Exp Dent. 2021; 13 (3)
Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review.
Güemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Garcia-Feijoo J, [...], Konstas AG.
Adv Ther. 2020; 37 (10)
DOI: 10.1007/s12325-020-01442-7
SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread.
2020-08-18 2020 other review-article; Review; Journal Article abstract-available 10.1007/s12325-020-01442-7 Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review. Güemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Garcia-Feijoo J, Arriola-Villalobos P, Martínez-de-la-Casa JM, Diaz-Valle D, Konstas AG. Adv Ther. 2020; 37 (10)
A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses.
Waagmeester A, Willighagen EL, Su AI, Kutmon M, [...], Koehorst JJ.
BMC Biol. 2021; 19 (1)
DOI: 10.1186/s12915-020-00940-y

Background

Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions.

Results

As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates.

Conclusions

Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).
2021-01-22 2021 other research-article; Journal Article abstract-available 10.1186/s12915-020-00940-y A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses. Waagmeester A, Willighagen EL, Su AI, Kutmon M, Gayo JEL, Fernández-Álvarez D, Groom Q, Schaap PJ, Verhagen LM, Koehorst JJ. BMC Biol. 2021; 19 (1)
The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data.
Malato J, Sotzny F, Bauer S, Freitag H, [...], Sepúlveda N.
Heliyon. 2021; 7 (8)
DOI: 10.1016/j.heliyon.2021.e07665
People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Given that this reporting agrees with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed at answering whether the expression of the human angiotensin-converting enzyme 2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in these patients. In particular, a low expression of ACE2 could be indicative of a high risk of developing COVID-19. We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients when compared to healthy controls. Accordingly, in newly collected data, there was evidence for a significant higher proportion of samples with an ACE2 expression below the limit of detection in patients than healthy controls. Altogether, patients with ME/CFS can be at a higher COVID-19 risk and, if so, they should be considered a priority group for vaccination by public health authorities. To further support this conclusion, similar research is recommended for other human cell entry receptors and cell types, namely, those cells targeted by the virus.
2021-07-29 2021 other research-article; Journal Article abstract-available 10.1016/j.heliyon.2021.e07665 The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data. Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. Heliyon. 2021; 7 (8)
After corona: there is life after the pandemic.
Tesarik J.
Reprod Biomed Online. 2020; 40 (6)
DOI: 10.1016/j.rbmo.2020.04.002
The current pandemic of Coronavirus Disease 2019 (COVID-19) has focused the attention of medical-care providers away from non-life-threatening diseases, including infertility. Although infertility does not jeopardize the physical survival of infertile couples, it does jeopardize their future quality of life. Human infertility can be caused by a number of factors, some of which are age-dependent, and their effects may become irreversible if appropriate measures are not taken in time to prevent irreversible childlessness. Accordingly, each case of infertility should be evaluated comprehensively to establish its position of priority. Assisted reproductive technology (ART) makes it possible to separate fertilization and pregnancy in time. Whereas pregnant women infected with coronavirus may have an increased risk of adverse neonatal outcomes, gametes do not transmit COVID-19. Thus, performing ovarian stimulation and fertilization without delay, freezing the resulting embryos and delaying embryo transfer until the end of the pandemic appears to be the best strategy at present.
2020-04-08 2020 other Comment; discussion; Journal Article abstract-available 10.1016/j.rbmo.2020.04.002 After corona: there is life after the pandemic. Tesarik J. Reprod Biomed Online. 2020; 40 (6)
Statins in COVID-19: Is there any foundation?☆ Estatinas en COVID-19: ¿existe algún fundamento?
Lima Martínez M, Contreras M, Marín W, D’Marco L.
Clínica e Investigación en Arteriosclerosis (English Edition). 2020; 32 (6)
DOI:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19.
2020-01-01 2020 other review-article; Review; Journal Article abstract-available Statins in COVID-19: Is there any foundation?☆ Estatinas en COVID-19: ¿existe algún fundamento? Lima Martínez M, Contreras M, Marín W, D’Marco L. Clínica e Investigación en Arteriosclerosis (English Edition). 2020; 32 (6)
A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus?
Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A.
Int J Antimicrob Agents. 2020; 56 (3)
DOI: 10.1016/j.ijantimicag.2020.106078
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria. Moreover, their antiviral properties have been previously studied, including against coronaviruses, where evidence of efficacy has been found. In the current race against time triggered by the COVID-19 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ. These could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low-molecular-weight heparin, aimed at preventing acute respiratory distress syndrome (ARDS)-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. This review also re-examines the real information provided by some of the published alarming reports, although concluding that cardiac toxicity should in any case be stringently monitored in patients receiving CQ/HCQ.
2020-07-04 2020 other research-article; Review; Journal Article abstract-available 10.1016/j.ijantimicag.2020.106078 A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus? Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A. Int J Antimicrob Agents. 2020; 56 (3)
Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits.
Pastor N, Collado MC, Manzoni P.
Nutrients. 2021; 13 (2)
DOI: 10.3390/nu13020464
The trend toward using phytonutrients and/or nutraceuticals (P/Ns) with the aim of impacting immune health has increased in recent years. The main reason is that properties of P/Ns are associated with possible immunomodulating effects in the prevention and complementary treatment of viral diseases, including COVID-19 and other respiratory infections. In the present review, we assess the scientific plausibility of specific P/Ns for this purpose of preventative and therapeutic interventions against COVID-19, with an emphasis on safety, validity, and evidence of efficacy against other viruses. Five potential candidates have been identified after reviewing available studies (in silico, in vitro, and in vivo) in which certain flavonoids have demonstrated a potential for use as adjuvant therapeutic agents against viral infections, including COVID-19. As these are often better tolerated than pharmacological treatments, their use could be more widely considered if additional detailed studies can validate the existing evidence.
2021-01-30 2021 other review-article; Review; Journal Article abstract-available 10.3390/nu13020464 Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits. Pastor N, Collado MC, Manzoni P. Nutrients. 2021; 13 (2)
SARS-CoV-2 antibody response eight months after vaccination with mRNA vaccines. Influence of prior SARS-CoV-2 exposure.
García-Cruces-Méndez JF, Corral-Gudino L, Del-Amo-Merino MP, Eiros-Bouza JM, [...], Domínguez-Gil González M.
Eur J Intern Med. 2022;
DOI: 10.1016/j.ejim.2022.01.011
2022-01-05 2022 other Letter 10.1016/j.ejim.2022.01.011 SARS-CoV-2 antibody response eight months after vaccination with mRNA vaccines. Influence of prior SARS-CoV-2 exposure. García-Cruces-Méndez JF, Corral-Gudino L, Del-Amo-Merino MP, Eiros-Bouza JM, Domínguez-Gil González M. Eur J Intern Med. 2022;
Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review.
Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O'Callaghan A, [...], Miró-Mur F.
Autoimmun Rev. 2020; 19 (7)
DOI: 10.1016/j.autrev.2020.102569
Severe Acute Respiratory Syndrome related to Coronavirus-2 (SARS-CoV-2), coronavirus disease-2019 (COVID-19) may cause severe illness in 20% of patients. This may be in part due to an uncontrolled immune-response to SARS-CoV-2 infection triggering a systemic hyperinflammatory response, the so-called "cytokine storm". The reduction of this inflammatory immune-response could be considered as a potential therapeutic target against severe COVID-19. The relationship between inflammation and clot activation must also be considered. Furthermore, we must keep in mind that currently, no specific antiviral treatment is available for SARS-CoV-2. While moderate-severe forms need in-hospital surveillance plus antivirals and/or hydroxychloroquine; in severe and life-threating subsets a high intensity anti-inflammatory and immunomodulatory therapy could be a therapeutic option. However, right data on the effectiveness of different immunomodulating drugs are scarce. Herein, we discuss the pathogenesis and the possible role played by drugs such as: antimalarials, anti-IL6, anti-IL-1, calcineurin and JAK inhibitors, corticosteroids, immunoglobulins, heparins, angiotensin-converting enzyme agonists and statins in severe COVID-19.
2020-05-03 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.autrev.2020.102569 Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review. Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O'Callaghan A, Pardos-Gea J, Quintana A, Mekinian A, Anunciacion-Llunell A, Miró-Mur F. Autoimmun Rev. 2020; 19 (7)
Epidemiology, pathophysiology, and classification of the neurological symptoms of post-COVID-19 syndrome Epidemiología, fisiopatología y clasificación de los síntomas neurológicos post-COVID
Carod-Artal F, García-Moncó J.
Neurology Perspectives. 2021; 1
DOI:

Introduction

Post-COVID-19 syndrome is a series of chronic signs and symptoms that may appear after SARS-CoV-2 infection, including fatigue, dyspnoea, chest pain, palpitations, anxiety, depression, and joint and muscle pain. The purpose of this study was to review the controversies on post-COVID-19 syndrome, the frequency of neurological symptoms, and the potential pathophysiological mechanisms.

Methods

We present a narrative review of studies published in PubMed since the beginning of the pandemic (January 2020–July 2021).

Results

Patients with history of COVID-19 have been found to present persistent neurological symptoms, including cognitive complaints, memory and concentration problems, headache, anosmia, ageusia, vertigo, and insomnia. Post-COVID-19 syndrome is a heterogeneous disease that lacks a universally accepted definition, which may explain the great variability in the estimated prevalence (2.3%–85%) and symptom duration. The criteria differentiating post-COVID-19 syndrome from chronic fatigue syndrome or critical illness syndrome are ambiguous. Risk factors include older age, female sex, certain comorbidities, and greater number of symptoms in the acute phase. The pathophysiology of the syndrome is largely unknown, although it is probably multifactorial, including immunological mechanisms, neural network dysfunction, neurotransmitter alterations, persistent viral damage, and functional impairment.

Conclusions

Post-COVID-19 syndrome may present after mild or even asymptomatic SARS-CoV-2 infection, causing limitations in activities of daily living and in quality of life. Further research will clarify the origin and most appropriate management of these neurological alterations.
2021-12-01 2021 other review-article; Review; Journal Article abstract-available Epidemiology, pathophysiology, and classification of the neurological symptoms of post-COVID-19 syndrome Epidemiología, fisiopatología y clasificación de los síntomas neurológicos post-COVID Carod-Artal F, García-Moncó J. Neurology Perspectives. 2021; 1
Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2.
Ruiz-Rodriguez P, Francés-Gómez C, Chiner-Oms Á, López MG, [...], Coscolla M.
mBio. 2021; 12 (6)
DOI: 10.1128/mbio.02315-21
We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data. IMPORTANCE We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including in vitro experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiological surveillance conducted months after the first observations revealed that both mutations did not successfully outcompete other variants and stopped circulating 9 months after their initial detection. Additionally, we evaluated the potential of both mutations to escape neutralizing antibodies, finding that the presence of these two mutations on their own is not likely to confer antibody escape. Our results provide an example of how newly emerged spike mutations can be assessed to better understand the risk posed by new variants and indicate that some spike mutations confer no clear advantage to the virus despite independently emerging multiple times and are eventually displaced by fitter variants.
2021-11-16 2021 fondo-covid Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/mbio.02315-21 Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2. Ruiz-Rodriguez P, Francés-Gómez C, Chiner-Oms Á, López MG, Jiménez-Serrano S, Cancino-Muñoz I, Ruiz-Hueso P, Torres-Puente M, Bracho MA, D'Auria G, Martinez-Priego L, Guerreiro M, Montero-Alonso M, Gómez MD, Piñana JL, SeqCOVID-SPAIN Consortium, González-Candelas F, Comas I, Marina A, Geller R, Coscolla M. mBio. 2021; 12 (6)
Subacute thyroiditis might be a complication triggered by SARS-CoV-2.
Ruano R, Zorzano-Martinez M, Campos A, Rius F, [...], Hernández M.
Endocrinol Diabetes Nutr (Engl Ed). 2021; 68 (10)
DOI: 10.1016/j.endien.2021.11.025
2021-12-01 2021 other Journal Article; Case Reports; case-report 10.1016/j.endien.2021.11.025 Subacute thyroiditis might be a complication triggered by SARS-CoV-2. Ruano R, Zorzano-Martinez M, Campos A, Rius F, Hernández M. Endocrinol Diabetes Nutr (Engl Ed). 2021; 68 (10)
Expansion of CD56dimCD16neg NK Cell Subset and Increased Inhibitory KIRs in Hospitalized COVID-19 Patients
Casado J, Moraga E, Vizcarra P, Velasco H, [...], Vallejo A.
Viruses. 2021; 14 (1)
DOI:
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection induces elevated levels of inflammatory cytokines, which are mainly produced by the innate response to the virus. The role of NK cells, which are potent producers of IFN-γ and cytotoxicity, has not been sufficiently studied in the setting of SARS-CoV-2 infection. We confirmed a different distribution of NK cell subsets in hospitalized COVID-19 patients despite their NK cell deficiency. The impairment of this innate defense is mainly focused on the cytotoxic capacity of the CD56dim NK cells. On the one hand, we found an expansion of the CD56dimCD16neg NK subset, lower cytotoxic capacities, and high frequencies of inhibitory 2DL1 and 2DL1/S1 KIR receptors in COVID-19 patients. On the other hand, the depletion of CD56dimCD16dim/bright NK cell subsets, high cytotoxic capacities, and high frequencies of inhibitory 2DL1 KIR receptors were found in COVID-19 patients. In contrast, no differences in the distribution of CD56bright NK cell subsets were found in this study. These alterations in the distribution and phenotype of NK cells might enhance the impairment of this crucial innate line of defense during COVID-19 infection.
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