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: 2022-12-07
Loading...
Funder
Fondo COVID19
Type
Articles
Preprints
Availability of
Abstract
Related data
Year
2022
2021
2020
2019
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
Myocardial Injury in COVID-19 and Its Implications in Short- and Long-Term Outcomes.
Izquierdo-Marquisá A, Cubero-Gallego H, Aparisi Á, Vaquerizo B, [...], Ribas-Barquet N.
Front Cardiovasc Med. 2022; 9
DOI: 10.3389/fcvm.2022.901245
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a pandemic with high mortality and morbidity rates. Clinical manifestation is widely variable, including asymptomatic or mild respiratory tract illness to severe pneumonia and death. Myocardial injury is a significant pathogenic feature of COVID-19 and it is associated with worse in-hospital outcomes, mainly due to a higher number of hospital readmissions, with over 50% mortality. These findings suggest that myocardial injury would identify COVID-19 patients with higher risk during active infection and mid-term follow-up. Potential contributors responsible for myocardial damage are myocarditis, vasculitis, acute inflammation, type 1 and type 2 myocardial infarction. However, there are few data about cardiac sequelae and its long-term consequences. Thus, the optimal screening tool for residual cardiac sequelae, clinical follow-up, and the benefits of a specific cardiovascular therapy during the convalescent phase remains unknown. This mini-review explores the different mechanisms of myocardial injury related to COVID-19 and its short and long-term implications.
2022-05-26 2022 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2022.901245 Myocardial Injury in COVID-19 and Its Implications in Short- and Long-Term Outcomes. Izquierdo-Marquisá A, Cubero-Gallego H, Aparisi Á, Vaquerizo B, Ribas-Barquet N. Front Cardiovasc Med. 2022; 9
Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies.
Barakat A, Mostafa A, Ali M, Al-Majid AM, [...], Elshaier YAMM.
Int J Mol Sci. 2022; 23 (19)
DOI: 10.3390/ijms231911861
The search for an effective anti-viral to inhibit COVID-19 is a challenge for the specialized scientific research community. This work investigated the anti-coronavirus activity for spirooxindole-based phenylsulfone cycloadducts in a single and combination protocols. The newly designed anti-SARS-CoV-2 therapeutics spirooxindoles synthesized by [3 + 2] cycloaddition reactions represent an efficient approach. One-pot multicomponent reactions between phenyl vinyl sulfone, substituted isatins, and amines afforded highly stereoselective anti-SARS-CoV-2 therapeutics spirooxindoles with three stereogenic centers. Herein, the newly synthesized spirooxindoles were assessed individually against the highly pathogenic human coronaviruses and proved to be highly potent and safer. Interestingly, the synergistic effect by combining the potent, tested spirooxindoles resulted in an improved antiviral activity as well as better host-cell safety. Compounds 4i and 4d represented the most potent activity against MERS-CoV with IC50 values of 11 and 23 µM, respectively. Both compounds 4c and 4e showed equipotent activity with the best IC50 against SARS-CoV-2 with values of 17 and 18 µM, respectively, then compounds 4d and 4k with IC50 values of 24 and 27 µM, respectively. Then, our attention oriented to perform a combination protocol as anti-SARS-CoV-2 for the best compounds with a different binding mode and accompanied with different pharmacophores. Combination of compound 4k with 4c and combination of compounds 4k with 4i proved to be more active and safer. Compounds 4k with 4i displayed IC50 = 3.275 µM and half maximal cytotoxic-concentration CC50 = 11832 µM. MD simulation of the most potential compounds as well as in silico ADMET properties were investigated. This study highlights the potential drug-like properties of spirooxindoles as a cocktail anti-coronavirus protocol.
2022-10-06 2022 other research-article; Journal Article abstract-available 10.3390/ijms231911861 Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies. Barakat A, Mostafa A, Ali M, Al-Majid AM, Domingo LR, Kutkat O, Moatasim Y, Zia K, Ul-Haq Z, Elshaier YAMM. Int J Mol Sci. 2022; 23 (19)
Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.
Fernández-de-Las-Peñas C, Arendt-Nielsen L, Díaz-Gil G, Gómez-Esquer F, [...], Giordano R.
Genes (Basel). 2022; 13 (11)
DOI: 10.3390/genes13111935
The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 virus into the cells, so polymorphisms could be important for the prognoses of long-COVID symptoms. Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) individuals who had been previously hospitalized due to COVID-19 were included. Three potential genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva samples of participants: ACE2 (rs2285666), ACE2 (rs2074192), TMPRSS2 (rs12329760), TMPRSS2 (rs2070788). Participants were asked to self-report the presence of any post-COVID defined as a symptom that started no later than one month after SARS-CoV-2 acute infection and whether the symptom persisted at the time of the study. At the time of the study (mean: 17.8, SD: 5.2 months after hospital discharge), 87.7% patients reported at least one symptom. Fatigue (62.8%), pain (39.9%) or memory loss (32.1%) were the most prevalent post-COVID symptoms. Overall, no differences in long-COVID symptoms were dependent on ACE2 rs2285666, ACE2 rs2074192, TMPRSS2 rs12329760, or TMPRSS2 rs2070788 genotypes. The four SNPs assessed, albeit previously associated with COVID-19 severity, do not predispose for developing long-COVID symptoms in people who were previously hospitalized due to COVID-19 during the first wave of the pandemic.
2022-10-24 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/genes13111935 Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors. Fernández-de-Las-Peñas C, Arendt-Nielsen L, Díaz-Gil G, Gómez-Esquer F, Gil-Crujera A, Gómez-Sánchez SM, Ambite-Quesada S, Palomar-Gallego MA, Pellicer-Valero OJ, Giordano R. Genes (Basel). 2022; 13 (11)
Potent Neutralizing Activity of Polyclonal Equine Antibodies against SARS-CoV-2 Variants of Concern.
Luczkowiak J, Radreau P, Nguyen L, Labiod N, [...], Delgado R.
J Infect Dis. 2022;
DOI: 10.1093/infdis/jiac331
Several monoclonal anti-SARS-CoV-2 antibodies (mAbs) have received emergency authorization for COVID-19 treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab')2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 VoCs tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab')2 antibodies as a novel therapeutic strategy against COVID-19.
2022-08-03 2022 other brief-report; Journal Article abstract-available 10.1093/infdis/jiac331 Potent Neutralizing Activity of Polyclonal Equine Antibodies against SARS-CoV-2 Variants of Concern. Luczkowiak J, Radreau P, Nguyen L, Labiod N, Lasala F, Veas F, Herbreteau CH, Delgado R. J Infect Dis. 2022;
Serum angiotensin-converting enzyme 2 as a potential biomarker for SARS-CoV-2 infection and vaccine efficacy.
Lennol MP, García-Ayllón MS, Esteban M, García-Arriaza J, [...], Sáez-Valero J.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.1001951
Various species of the SARS-CoV-2 host cell receptor, the angiotensin-converting enzyme 2 (ACE2), are present in serum, which may result from virus entry and subsequent proteolytic processing of the membrane receptor. We have recently demonstrated changes of particular ACE2 species in virus infected humans, either cleaved fragments or circulating full-length species. Here, we further explore the potential of serum ACE2 as a biomarker to test SARS-CoV-2 infection and vaccine efficacy in virus susceptible transgenic K18-hACE2 mice expressing human ACE2. First, in serum samples derived from K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2, we observed an increase in the levels of cleaved ACE2 fragment at day 2 post-challenge, which may represent the subsequent proteolytic processing through virus entry. These elevated levels were maintained until the death of the animals at day 6 post-challenge. The circulating full-length ACE2 form displayed a sizable peak at day 4, which declined at day 6 post-challenge. Noticeably, immunization with two doses of the MVA-CoV2-S vaccine candidate prevented ACE2 cleaved changes in serum of animals challenged with a lethal dose of SARS-CoV-2. The efficacy of the MVA-CoV2-S was extended to vaccinated mice after virus re-challenge. These findings highlight that ACE2 could be a potential serum biomarker for disease progression and vaccination against SARS-CoV-2.
2022-10-12 2022 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.3389/fimmu.2022.1001951 Serum angiotensin-converting enzyme 2 as a potential biomarker for SARS-CoV-2 infection and vaccine efficacy. Lennol MP, García-Ayllón MS, Esteban M, García-Arriaza J, Sáez-Valero J. Front Immunol. 2022; 13
Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses.
Sander AL, Moreira-Soto A, Yordanov S, Toplak I, [...], Drexler JF.
Commun Biol. 2022; 5 (1)
DOI: 10.1038/s42003-022-03421-w
The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome-related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2.
2022-05-30 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s42003-022-03421-w Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses. Sander AL, Moreira-Soto A, Yordanov S, Toplak I, Balboni A, Ameneiros RS, Corman V, Drosten C, Drexler JF. Commun Biol. 2022; 5 (1)
Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology.
Sebastián-Martín A, Sánchez BG, Mora-Rodríguez JM, Bort A, [...], Díaz-Laviada I.
Biomedicines. 2022; 10 (8)
DOI: 10.3390/biomedicines10082026
DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology. Due to the pathogenetic links between COVID-19 and diabetes mellitus and the hyperinflammatory response, with the hallmark cytokine storm developed very often during the disease, we dive deep into the functions of DPP4 on carbohydrate metabolism and immune system regulation. We show that the broad spectrum of functions regulated by DPP4 is performed both as a protease enzyme, as well as an interacting partner of other molecules on the cell surface. In addition, we provide an update of the DPP4 inhibitors approved by the EMA and/or the FDA, together with the newfangled approval of generic drugs (in 2021 and 2022). This review will also cover the effects of DPP4 inhibitors (i.e., gliptins) on the progression of SARS-CoV-2 infection, showing the role of DPP4 in this disturbing disease.
2022-08-19 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10082026 Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology. Sebastián-Martín A, Sánchez BG, Mora-Rodríguez JM, Bort A, Díaz-Laviada I. Biomedicines. 2022; 10 (8)
Network pharmacology reveals multitarget mechanism of action of drugs to be repurposed for COVID-19.
Alegría-Arcos M, Barbosa T, Sepúlveda F, Combariza G, [...], Ramírez D.
Front Pharmacol. 2022; 13
DOI: 10.3389/fphar.2022.952192
The coronavirus disease 2019 pandemic accelerated drug/vaccine development processes, integrating scientists all over the globe to create therapeutic alternatives against this virus. In this work, we have collected information regarding proteins from SARS-CoV-2 and humans and how these proteins interact. We have also collected information from public databases on protein-drug interactions. We represent this data as networks that allow us to gain insights into protein-protein interactions between both organisms. With the collected data, we have obtained statistical metrics of the networks. This data analysis has allowed us to find relevant information on which proteins and drugs are the most relevant from the network pharmacology perspective. This method not only allows us to focus on viral proteins as the main targets for COVID-19 but also reveals that some human proteins could be also important in drug repurposing campaigns. As a result of the analysis of the SARS-CoV-2-human interactome, we have identified some old drugs, such as disulfiram, auranofin, gefitinib, suloctidil, and bromhexine as potential therapies for the treatment of COVID-19 deciphering their potential complex mechanism of action.
2022-08-17 2022 other research-article; Journal Article abstract-available 10.3389/fphar.2022.952192 Network pharmacology reveals multitarget mechanism of action of drugs to be repurposed for COVID-19. Alegría-Arcos M, Barbosa T, Sepúlveda F, Combariza G, González J, Gil C, Martínez A, Ramírez D. Front Pharmacol. 2022; 13
COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity.
David S, Dorado G, Duarte EL, David-Bosne S, [...], Rebelo-de-Andrade H.
Immunogenetics. 2022; 74 (4)
DOI: 10.1007/s00251-022-01261-w
COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million human beings worldwide, causing an unprecedented coronavirus pandemic. Currently, the international scientific community is engaged in elucidating the molecular mechanisms of the pathophysiology of SARS-CoV-2 infection as a basis of scientific developments for the future control of COVID-19. Global exome and genome analysis efforts work to define the human genetics of protective immunity to SARS-CoV-2 infection. Here, we review the current knowledge regarding the SARS-CoV-2 infection, the implications of COVID-19 to Public Health and discuss genotype to phenotype association approaches that could be exploited through the selection of candidate genes to identify the genetic determinants of severe COVID-19.
2022-03-29 2022 other review-article; Review; Journal Article abstract-available 10.1007/s00251-022-01261-w COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity. David S, Dorado G, Duarte EL, David-Bosne S, Trigueiro-Louro J, Rebelo-de-Andrade H. Immunogenetics. 2022; 74 (4)
Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail.
Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, [...], Simal-Gandara J.
Inflamm Res. 2022; 71 (10-11)
DOI: 10.1007/s00011-022-01615-w

Introduction

Fenofibrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses anti-inflammatory, antioxidant, and anti-thrombotic properties. Fenofibrate is effective against a variety of viral infections and different inflammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofibrate in the pathogenesis of SARS-CoV-2 and related complications.

Results

By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofibrate can reduce SARS-CoV-2 entry in human cells Fenofibrate also suppresses inflammatory signaling pathways, which decreases SARS-CoV-2 infection-related inflammatory alterations. In conclusion, fenofibrate anti-inflammatory, antioxidant, and antithrombotic capabilities may help to minimize the inflammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofibrate can directly reduce the risk of SARS-CoV-2 infection.

Conclusions

As a result, fenofibrate could be a potential treatment approach for COVID-19 control.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1007/s00011-022-01615-w Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail. Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, AboKamer AM, Batiha GE, Simal-Gandara J. Inflamm Res. 2022; 71 (10-11)
Susceptibility of Domestic Goat (Capra aegagrus hircus) to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.351/Beta Variant.
Fernández-Bastit L, Roca N, Romero-Durana M, Rodon J, [...], Lorca-Oró C.
Viruses. 2022; 14 (9)
DOI: 10.3390/v14092002
A wide range of animal species are susceptible to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Natural and/or experimental infections have been reported in pet, zoo, farmed and wild animals. Interestingly, some SARS-CoV-2 variants, such as B.1.1.7/Alpha, B.1.351/Beta, and B.1.1.529/Omicron, were demonstrated to infect some animal species not susceptible to classical viral variants. The present study aimed to elucidate if goats (Capra aegagrus hircus) are susceptible to the B.1.351/Beta variant. First, an in silico approach was used to predict the affinity between the receptor-binding domain of the spike protein of SARS-CoV-2 B.1.351/Beta variant and angiotensin-converting enzyme 2 from goats. Moreover, we performed an experimental inoculation with this variant in domestic goat and showed evidence of infection. SARS-CoV-2 was detected in nasal swabs and tissues by RT-qPCR and/or immunohistochemistry, and seroneutralisation was confirmed via ELISA and live virus neutralisation assays. However, the viral amount and tissue distribution suggest a low susceptibility of goats to the B.1.351/Beta variant. Therefore, although monitoring livestock is advisable, it is unlikely that goats play a role as SARS-CoV-2 reservoir species, and they are not useful surrogates to study SARS-CoV-2 infection in farmed animals.
2022-09-09 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v14092002 Susceptibility of Domestic Goat (<i>Capra aegagrus hircus</i>) to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.351/Beta Variant. Fernández-Bastit L, Roca N, Romero-Durana M, Rodon J, Cantero G, García Ó, López C, Pérez M, López R, Carrillo J, Izquierdo-Useros N, Blanco J, Clotet B, Pujols J, Vergara-Alert J, Segalés J, Lorca-Oró C. Viruses. 2022; 14 (9)
The Finding of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in a Wild Eurasian River Otter (Lutra lutra) Highlights the Need for Viral Surveillance in Wild Mustelids.
Padilla-Blanco M, Aguiló-Gisbert J, Rubio V, Lizana V, [...], Rubio-Guerri C.
Front Vet Sci. 2022; 9
DOI: 10.3389/fvets.2022.826991
Animals have been involved in the three known outbreaks of severe respiratory syndromes due to coronaviruses (years 2005, 2012, and 2019). The pandemic nature of the SARS-CoV-2 outbreak increases the likelihood of infection from humans of susceptible animal species that, thus, could become secondary viral hosts and even disease reservoirs. We present evidence of spillover infection of wild mustelids by reporting the presence of SARS-CoV-2 in a Eurasian river otter found near a water reservoir in the Valencian Community (Spain). We detected the virus using two different commercial RTqPCR assays on RNA extracted from the nasopharynx (swabbing) and from lung tissue and mediastinal lymph node homogenates. The corresponding samples from two additional otters from distant sites tested negative in identical assays. The diagnosis in the positive otter was confirmed by two-tube RT-PCR assay in which RNA was first retrotranscribed, and then specific regions of the spike (S), nucleocapsid (N), and ORF10 genes were separately amplified from the produced cDNA, followed by electrophoretic visualization and Sanger sequencing. The sequences of the amplified products revealed some non-synonymous changes in the N and ORF10 partial sequences, relative to the consensus sequence. These changes, identified already in human patient samples, point to human origin of the virus, although their specific combination was unique. These findings, together with our previous report of SARS-CoV-2 infection of feral American mink, highlight the need for SARS-CoV-2 surveillance of wild or feral mustelids to evaluate the risk that these animals could become SARS-CoV-2 reservoirs.
2022-03-31 2022 other brief-report; Journal Article abstract-available 10.3389/fvets.2022.826991 The Finding of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in a Wild Eurasian River Otter (<i>Lutra lutra</i>) Highlights the Need for Viral Surveillance in Wild Mustelids. Padilla-Blanco M, Aguiló-Gisbert J, Rubio V, Lizana V, Chillida-Martínez E, Cardells J, Maiques E, Rubio-Guerri C. Front Vet Sci. 2022; 9
Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern.
Tyrkalska SD, Martínez-López A, Arroyo AB, Martínez-Morcillo FJ, [...], Mulero V.
Sci Adv. 2022; 8 (37)
DOI: 10.1126/sciadv.abo0732
The coronavirus disease 2019 (COVID-19) pandemic turned the whole world upside down in a short time. One of the main challenges faced has been to understand COVID-19-associated life-threatening hyperinflammation, the so-called cytokine storm syndrome (CSS). We report here the proinflammatory role of Spike (S) proteins from different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern in zebrafish. We found that wild-type/Wuhan variant S1 (S1WT) promoted neutrophil and macrophage recruitment, local and systemic hyperinflammation, emergency myelopoiesis, and hemorrhages. In addition, S1γ was more proinflammatory S1δ was less proinflammatory than S1WT, and, notably, S1β promoted delayed and long-lasting inflammation. Pharmacological inhibition of the canonical inflammasome alleviated S1-induced inflammation and emergency myelopoiesis. In contrast, genetic inhibition of angiotensin-converting enzyme 2 strengthened the proinflammatory activity of S1, and angiotensin (1-7) fully rescued S1-induced hyperinflammation and hemorrhages. These results shed light into the mechanisms orchestrating the COVID-19-associated CSS and the host immune response to different SARS-CoV-2 S protein variants.
2022-09-16 2022 other research-article; Journal Article abstract-available 10.1126/sciadv.abo0732 Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern. Tyrkalska SD, Martínez-López A, Arroyo AB, Martínez-Morcillo FJ, Candel S, García-Moreno D, Mesa-Del-Castillo P, Cayuela ML, Mulero V. Sci Adv. 2022; 8 (37)
Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants.
Monteil V, Eaton B, Postnikova E, Murphy M, [...], Penninger JM.
EMBO Mol Med. 2022; 14 (8)
DOI: 10.15252/emmm.202115230
The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.
2022-07-04 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.15252/emmm.202115230 Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants. Monteil V, Eaton B, Postnikova E, Murphy M, Braunsfeld B, Crozier I, Kricek F, Niederhöfer J, Schwarzböck A, Breid H, Devignot S, Klingström J, Thålin C, Kellner MJ, Christ W, Havervall S, Mereiter S, Knapp S, Sanchez Jimenez A, Bugajska-Schretter A, Dohnal A, Ruf C, Gugenberger R, Hagelkruys A, Montserrat N, Kozieradzki I, Hasan Ali O, Stadlmann J, Holbrook MR, Schmaljohn C, Oostenbrink C, Shoemaker RH, Mirazimi A, Wirnsberger G, Penninger JM. EMBO Mol Med. 2022; 14 (8)
COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.
Lundstrom K, Hromić-Jahjefendić A, Bilajac E, Aljabali AAA, [...], Barh D.
Cell Signal. 2023; 101
DOI: 10.1016/j.cellsig.2022.110495
The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.
2022-10-15 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.cellsig.2022.110495 COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity. Lundstrom K, Hromić-Jahjefendić A, Bilajac E, Aljabali AAA, Baralić K, Sabri NA, Shehata EM, Raslan M, Ferreira ACBH, Orlandi L, Serrano-Aroca Á, Tambuwala MM, Uversky VN, Azevedo V, Alzahrani KJ, Alsharif KF, Halawani IF, Alzahrani FM, Redwan EM, Barh D. Cell Signal. 2023; 101
Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2.
Tamayo-Velasco Á, Jiménez García MT, Sanchez Rodríguez A, Hijas Villaizan M, [...], Miramontes-González JP.
Med Clin (Engl Ed). 2022; 159 (1)
DOI: 10.1016/j.medcle.2021.06.028

Background and objectives

In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution.

Patients and methods

A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index.

Results

Patients in group A had a higher Charlson Index (P = .037), rate of lymphopenia (P = .039) and thrombopenia (P = .014), and hospital mortality (P = .044). Blood group A was an independent factor associated with the Charlson Index (B 0.582, 95% CI 0.02-1.14, P = .041).

Conclusions

Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality.
2022-06-29 2022 other Case Reports; case-report abstract-available 10.1016/j.medcle.2021.06.028 Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2. Tamayo-Velasco Á, Jiménez García MT, Sanchez Rodríguez A, Hijas Villaizan M, Carretero Gómez J, Miramontes-González JP. Med Clin (Engl Ed). 2022; 159 (1)
Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404.
Fàbrega-Ferrer M, Herrera-Morandé A, Muriel-Goñi S, Pérez-Saavedra J, [...], Coll M.
Antiviral Res. 2022; 208
DOI: 10.1016/j.antiviral.2022.105458
Severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) pose a threat to global public health. The 3C-like main protease (Mpro), which presents structural similarity with the active site domain of enterovirus 3C protease, is one of the best-characterized drug targets of these viruses. Here we studied the antiviral activity of the orally bioavailable enterovirus protease inhibitor AG7404 against SARS-CoV-1 and SARS-CoV-2 from a structural, biochemical, and cellular perspective, comparing it with the related molecule rupintrivir (AG7800). Crystallographic structures of AG7404 in complex with SARS-CoV-1 Mpro and SARS-CoV-2 Mpro and of rupintrivir in complex with SARS-CoV-2 Mpro were solved, revealing that all protein residues interacting with the inhibitors are conserved between the two proteins. A detailed analysis of protein-inhibitor interactions indicates that AG7404 has a better fit to the active site of the target protease than rupintrivir. This observation was further confirmed by biochemical FRET assays showing IC50 values of 47 μM and 101 μM for AG7404 and rupintrivir, respectively, in the case of SARS-CoV-2 Mpro. Equivalent IC50 values for SARS-CoV-1 also revealed greater inhibitory capacity of AG7404, with a value of 29 μM vs. 66 μM for rupintrivir. Finally, the antiviral activity of the two inhibitors against SARS-CoV-2 was confirmed in a human cell culture model of SARS-CoV-2 infection, although rupintrivir showed a higher potency and selectivity index in this assay.
2022-11-03 2022 other brief-report; Journal Article abstract-available 10.1016/j.antiviral.2022.105458 Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404. Fàbrega-Ferrer M, Herrera-Morandé A, Muriel-Goñi S, Pérez-Saavedra J, Bueno P, Castro V, Garaigorta U, Gastaminza P, Coll M. Antiviral Res. 2022; 208
Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths.
Ortega MA, García-Montero C, Fraile-Martinez O, Colet P, [...], Sarría-Santamera A.
J Pers Med. 2022; 12 (6)
DOI: 10.3390/jpm12060995
Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.
2022-06-18 2022 other review-article; Review; Journal Article abstract-available 10.3390/jpm12060995 Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths. Ortega MA, García-Montero C, Fraile-Martinez O, Colet P, Baizhaxynova A, Mukhtarova K, Alvarez-Mon M, Kanatova K, Asúnsolo A, Sarría-Santamera A. J Pers Med. 2022; 12 (6)
European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis.
Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, [...], Williams B.
Cardiovasc Res. 2022; 118 (6)
DOI: 10.1093/cvr/cvab342

Aims

Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19.

Methods and results

A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19.

Conclusion

This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
2022-05-01 2022 other research-article; Review; Journal Article abstract-available 10.1093/cvr/cvab342 European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis. Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, Arbelo E, Barbato E, Bartorelli AL, Baumbach A, Behr ER, Berti S, Bueno H, Capodanno D, Cappato R, Chieffo A, Collet JP, Cuisset T, de Simone G, Delgado V, Dendale P, Dudek D, Edvardsen T, Elvan A, González-Juanatey JR, Gori M, Grobbee D, Guzik TJ, Halvorsen S, Haude M, Heidbuchel H, Hindricks G, Ibanez B, Karam N, Katus H, Klok FA, Konstantinides SV, Landmesser U, Leclercq C, Leonardi S, Lettino M, Marenzi G, Mauri J, Metra M, Morici N, Mueller C, Petronio AS, Polovina MM, Potpara T, Praz F, Prendergast B, Prescott E, Price S, Pruszczyk P, Rodríguez-Leor O, Roffi M, Romaguera R, Rosenkranz S, Sarkozy A, Scherrenberg M, Seferovic P, Senni M, Spera FR, Stefanini G, Thiele H, Tomasoni D, Torracca L, Touyz RM, Wilde AA, Williams B. Cardiovasc Res. 2022; 118 (6)
Current Treatments for COVID-19: Application of Supercritical Fluids in the Manufacturing of Oral and Pulmonary Formulations.
Ruiz HK, Serrano DR, Calvo L, Cabañas A.
Pharmaceutics. 2022; 14 (11)
DOI: 10.3390/pharmaceutics14112380
Even though more than two years have passed since the emergence of COVID-19, the research for novel or repositioned medicines from a natural source or chemically synthesized is still an unmet clinical need. In this review, the application of supercritical fluids to the development of novel or repurposed medicines for COVID-19 and their secondary bacterial complications will be discussed. We envision three main applications of the supercritical fluids in this field: (i) drug micronization, (ii) supercritical fluid extraction of bioactives and (iii) sterilization. The supercritical fluids micronization techniques can help to improve the aqueous solubility and oral bioavailability of drugs, and consequently, the need for lower doses to elicit the same pharmacological effects can result in the reduction in the dose administered and adverse effects. In addition, micronization between 1 and 5 µm can aid in the manufacturing of pulmonary formulations to target the drug directly to the lung. Supercritical fluids also have enormous potential in the extraction of natural bioactive compounds, which have shown remarkable efficacy against COVID-19. Finally, the successful application of supercritical fluids in the inactivation of viruses opens up an opportunity for their application in drug sterilization and in the healthcare field.
2022-11-04 2022 other review-article; Review; Journal Article abstract-available 10.3390/pharmaceutics14112380 Current Treatments for COVID-19: Application of Supercritical Fluids in the Manufacturing of Oral and Pulmonary Formulations. Ruiz HK, Serrano DR, Calvo L, Cabañas A. Pharmaceutics. 2022; 14 (11)
Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge.
Milton-Laskibar I, Trepiana J, Macarulla MT, Gómez-Zorita S, [...], Portillo MP.
J Physiol Biochem. 2022;
DOI: 10.1007/s13105-022-00926-0
The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.
2022-11-08 2022 other review-article; Review; Journal Article abstract-available 10.1007/s13105-022-00926-0 Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge. Milton-Laskibar I, Trepiana J, Macarulla MT, Gómez-Zorita S, Arellano-García L, Fernández-Quintela A, Portillo MP. J Physiol Biochem. 2022;
Excretion and viability of SARS-CoV-2 in feces and its association with the clinical outcome of COVID-19.
Cerrada-Romero C, Berastegui-Cabrera J, Camacho-Martínez P, Goikoetxea-Aguirre J, [...], Sánchez-Céspedes J.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-11439-7
The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in stools. In addition, we aimed to identify clinical factors associated with the detection of SARS-CoV-2 RNA in feces, and to determine if its presence is associated with an unfavorable clinical outcome, defined as intensive care unit (ICU) admission and/or death. A prospective multicenter cohort study of COVID-19 adult patients, with confirmed SARS-CoV-2 infection by RT-PCR assay in nasopharyngeal (NP) swabs admitted to four hospitals in Spain, from March 2020 to February 2021. Sixty-two adult COVID-19 patients had stool samples collected at admission and/or during the follow up, with a total of 79 stool samples. SARS-CoV-2 RNA was detected in stool samples from 27 (43.5%) out of the 62 patients. Replicative virus, measured by the generation of cytopathic effect in cell culture and subsequent RT-PCR confirmation of a decrease in the Ct values, was not found in any of these stool samples. Fecal virus excretion was not associated with the presence of gastrointestinal symptoms, or with differences in the evolution of COVID-19 patients. Our results suggest that SARS-CoV-2 replicative capacity is null or very limited in stool samples, and thus, the fecal-oral transmission of SARS-CoV-2 as an alternative infection route is highly unlikely. In our study, the detection of SARS-CoV-2 RNA in feces at the beginning of the disease is not associated with any clinical factor nor with an unfavorable clinical outcome.
2022-05-05 2022 fondo-covid Research Support, Non-U.S. Gov't; research-article; Multicenter Study; Journal Article abstract-available 10.1038/s41598-022-11439-7 Excretion and viability of SARS-CoV-2 in feces and its association with the clinical outcome of COVID-19. Cerrada-Romero C, Berastegui-Cabrera J, Camacho-Martínez P, Goikoetxea-Aguirre J, Pérez-Palacios P, Santibáñez S, José Blanco-Vidal M, Valiente A, Alba J, Rodríguez-Álvarez R, Pascual Á, Oteo JA, Miguel Cisneros J, Pachón J, Casas-Flecha I, Cordero E, Pozo F, Sánchez-Céspedes J. Sci Rep. 2022; 12 (1)
SARS-CoV-2-specific antibodies and neutralization capacity in breast milk following infection vs vaccination.
Leung HYH, Leung BW, Gil MM, Rolle V, [...], Poon LC.
Ultrasound Obstet Gynecol. 2022; 60 (3)
DOI: 10.1002/uog.24965
Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been found in breast milk following both natural SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination. This was a prospective study to evaluate the temporal changes in amount and neutralization capacity of anti-SARS-CoV-2 antibodies in breast milk stimulated by natural infection and by vaccination. Serial breast milk samples were collected from postnatal women who were recruited through convenience sampling. We found a rapid increase in neutralizing SARS-CoV-2-specific antibodies in breast milk from both study groups. Amongst the infection group, the median immunoglobulin A (IgA) level was 16.99 (range, 0-86.56) ng/mL and median binding capacity was 33.65% (range, 0-67.65%), while in the vaccination group these were 30.80 (range, 0-77.40) ng/mL and 23.80% (range, 0-42.80%), respectively. In both groups, both binding capacity and IgA levels decreased progressively over time after peaking. Neutralizing activity had become undetectable by about 150 days after the first dose of the vaccine, but a vaccine booster dose restored secretion of neutralizing IgA, albeit with different levels of response in different individuals. This highlights the importance of the vaccine booster dose in sustaining neutralizing antibody levels in breast milk, which may potentially provide protection for very young children, who cannot receive the COVID-19 vaccine. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
2022-09-01 2022 other Case Reports; case-report abstract-available 10.1002/uog.24965 SARS-CoV-2-specific antibodies and neutralization capacity in breast milk following infection vs vaccination. Leung HYH, Leung BW, Gil MM, Rolle V, Moungmaithong S, Wang CC, Poon LC. Ultrasound Obstet Gynecol. 2022; 60 (3)
N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions
Izquierdo-Alonso J, Pérez-Rial S, Rivera C, Peces-Barba G.
J Infect Public Health. 2022; 15 (12)
DOI:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.
2022-11-12 2022 other review-article; Review; Journal Article abstract-available N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions Izquierdo-Alonso J, Pérez-Rial S, Rivera C, Peces-Barba G. J Infect Public Health. 2022; 15 (12)
Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection.
Pérez P, Astorgano D, Albericio G, Flores S, [...], García-Arriaza J.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.995235
Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.
2022-09-12 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.995235 Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection. Pérez P, Astorgano D, Albericio G, Flores S, Sánchez-Cordón PJ, Luczkowiak J, Delgado R, Casasnovas JM, Esteban M, García-Arriaza J. Front Immunol. 2022; 13
A study of viral pathogens in bat species in the Iberian Peninsula: identification of new coronavirus genetic variants.
Moraga-Fernández A, Sánchez-Sánchez M, Queirós J, Lopes AM, [...], Fernández de Mera IG.
Int J Vet Sci Med. 2022; 10 (1)
DOI: 10.1080/23144599.2022.2139985
Bats have long been associated with multiple pathogens, including viruses affecting humans such as henipaviruses, filoviruses, bunyaviruses and coronaviruses. The alpha and beta coronaviruses genera can infect most mammalian species. Among them, betacoronavirus SARS-CoV, MERS-CoV and SARS-CoV-2, which have caused the three major pandemics in the last two decades, have been proposed to originate in bats. In this study, 194 oral swabs from 22 bats species sampled in 19 locations of the Iberian Peninsula were analysed and characterized by three different PCR tests (coronavirus generic real-time RT-PCR, multiplex conventional PCR, and SARS-CoV-2 specific real-time RT-PCR) to detect bat coronaviruses. Screening with coronavirus generic PCR showed 102 positives out of 194 oral swabs analysed. Then, metabarcoding with multiplex PCR amplified 15 positive samples. Most of the coronaviruses detected in this study belong to alphacoronavirus (α-CoV) genus, with multiple alphacoronaviruses identified by up to five different genetic variants coexisting in the same bat. One of the positive samples identified in a Miniopterus schreibersii bat positive for the generic coronavirus PCR and the specific SARS-CoV-2 PCR was classified as betacoronavirus (-CoV) through phylogenetic analysis. These results support the rapid evolution of coronaviruses to generate new genomic potentially pathogenic variants likely through co-infection and recombination.
2022-11-03 2022 other research-article; Journal Article abstract-available 10.1080/23144599.2022.2139985 A study of viral pathogens in bat species in the Iberian Peninsula: identification of new coronavirus genetic variants. Moraga-Fernández A, Sánchez-Sánchez M, Queirós J, Lopes AM, Vicente J, Pardavila X, Sereno-Cadierno J, Alves PC, de la Fuente J, Fernández de Mera IG. Int J Vet Sci Med. 2022; 10 (1)
Analysis of transcriptomic responses to SARS-CoV-2 reveals plausible defective pathways responsible for increased susceptibility to infection and complications and helps to develop fast-track repositioning of drugs against COVID-19.
deAndrés-Galiana EJ, Fernández-Martínez JL, Álvarez-Machancoses Ó, Bea G, [...], Kloczkowski A.
Comput Biol Med. 2022; 149
DOI: 10.1016/j.compbiomed.2022.106029

Background

To understand the transcriptomic response to SARS-CoV-2 infection, is of the utmost importance to design diagnostic tools predicting the severity of the infection.

Methods

We have performed a deep sampling analysis of the viral transcriptomic data oriented towards drug repositioning. Using different samplers, the basic principle of this methodology the biological invariance, which means that the pathways altered by the disease, should be independent on the algorithm used to unravel them.

Results

The transcriptomic analysis of the altered pathways, reveals a distinctive inflammatory response and potential side effects of infection. The virus replication causes, in some cases, acute respiratory distress syndrome in the lungs, and affects other organs such as heart, brain, and kidneys. Therefore, the repositioned drugs to fight COVID-19 should, not only target the interferon signalling pathway and the control of the inflammation, but also the altered genetic pathways related to the side effects of infection. We also show via Principal Component Analysis that the transcriptome signatures are different from influenza and RSV. The gene COL1A1, which controls collagen production, seems to play a key/vital role in the regulation of the immune system. Additionally, other small-scale signature genes appear to be involved in the development of other COVID-19 comorbidities.

Conclusions

Transcriptome-based drug repositioning offers possible fast-track antiviral therapy for COVID-19 patients. It calls for additional clinical studies using FDA approved drugs for patients with increased susceptibility to infection and with serious medical complications.
2022-08-30 2022 other research-article; Research Support, U.S. Gov't, Non-P.H.S.; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1016/j.compbiomed.2022.106029 Analysis of transcriptomic responses to SARS-CoV-2 reveals plausible defective pathways responsible for increased susceptibility to infection and complications and helps to develop fast-track repositioning of drugs against COVID-19. deAndrés-Galiana EJ, Fernández-Martínez JL, Álvarez-Machancoses Ó, Bea G, Galmarini CM, Kloczkowski A. Comput Biol Med. 2022; 149
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: 10.3390/biom12010076
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.
2022-01-05 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/biom12010076 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)
The current status of COVID-19 vaccines. A scoping review.
Rueda-Fernández M, Melguizo-Rodríguez L, Costela-Ruiz VJ, González-Acedo A, [...], Illescas-Montes R.
Drug Discov Today. 2022; 27 (11)
DOI: 10.1016/j.drudis.2022.08.004
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new disease that has led to a worldwide pandemic, resulting in millions of deaths and a high economic burden. Here, we analyze the current status of preventive vaccines authorized by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Published clinical trials have shown the effectiveness of mRNA (BNT162b2 and Spikevax), adenovirus vector-based (Ad26.COV2.S and ChAdOx1 nCoV-19), and recombinant protein S (NVX-CoV2373) vaccines to be between 52.9% and 100%. The most-frequent adverse effects include local pain, fatigue, headache, or chills. Serious events are associated with Ad26.COV2.S and ChAdOx1 nCoV-19 vaccines.
2022-08-19 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.drudis.2022.08.004 The current status of COVID-19 vaccines. A scoping review. Rueda-Fernández M, Melguizo-Rodríguez L, Costela-Ruiz VJ, González-Acedo A, Ramos-Torrecillas J, Illescas-Montes R. Drug Discov Today. 2022; 27 (11)
Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics
Singh A, Katz A, Maharajan R, Gadicherla A, [...], Luch A.
Sci Total Environ. 2022;
DOI:
Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 μm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability. Graphical abstract Unlabelled Image
2022-11-25 2022 other research-article; Journal Article abstract-available Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics Singh A, Katz A, Maharajan R, Gadicherla A, Richter M, Heyda J, del Pino P, Laux P, Luch A. Sci Total Environ. 2022;
A year living with SARS-CoV-2: an epidemiological overview of viral lineage circulation by whole-genome sequencing in Barcelona city (Catalonia, Spain).
Andrés C, Piñana M, Borràs-Bermejo B, González-Sánchez A, [...], Antón A.
Emerg Microbes Infect. 2022; 11 (1)
DOI: 10.1080/22221751.2021.2011617
Herein, we describe the genetic diversity of circulating SARS-CoV-2 viruses by whole-genome sequencing (WGS) in Barcelona city (Catalonia, Spain) throughout the first four pandemic waves. From weeks 11/2020-24/2021, SARS-CoV-2-positive respiratory samples were randomly selected per clinical setting (80% from primary care or 20% from the hospital), age group, and week. WGS was performed following the ARTICv3 protocol on MiSeq or NextSeq2000 Illumina platforms. Nearly complete consensus sequences were used for genetic characterization based on GISAID and PANGOLIN nomenclatures. From 2475 samples, 2166 (87%) were fully sequenced (78% from primary care and 22% from hospital settings). Multiple genetic lineages were co-circulating, but four were predominant at different periods. While B.1.5 (50.68%) and B.1.1 (32.88%) were the major lineages during the first pandemic wave, B.1.177 (66.85%) and B.1.1.7 (83.80%) were predominant during the second, third, and fourth waves, respectively. Almost all (96.4%) were carrying D614G mutation in the S protein, with additional mutations that define lineages or variants. But some mutations of concern, such as E484K from B.1.351 and P.1 lineages are currently under monitoring, together with those observed in the receptor-binding domain or N-terminal domain, such as L452R and T478K from B.1.617.2 lineage. The fact that a predominant lineage was observed in each pandemic wave suggests advantageous properties over other contemporary co-circulating variants. This genetic variability should be monitored, especially when a massive vaccination campaign is ongoing because the potential selection and emergence of novel antigenic SARS-CoV-2 strains related to immunological escapement events.
2022-12-01 2022 other research-article; Journal Article abstract-available 10.1080/22221751.2021.2011617 A year living with SARS-CoV-2: an epidemiological overview of viral lineage circulation by whole-genome sequencing in Barcelona city (Catalonia, Spain). Andrés C, Piñana M, Borràs-Bermejo B, González-Sánchez A, García-Cehic D, Esperalba J, Rando A, Zules-Oña RG, Campos C, Codina MG, Blanco-Grau A, Colomer-Castell S, Martín MC, Castillo C, García-Comuñas K, Vásquez-Mercado R, Martins-Martins R, Saubi N, Campins-Martí M, Pumarola T, Quer J, Antón A. Emerg Microbes Infect. 2022; 11 (1)
Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells.
Aicher SM, Streicher F, Chazal M, Planas D, [...], Jouvenet N.
J Virol. 2022; 96 (14)
DOI: 10.1128/jvi.00608-22
Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. IMPORTANCE Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.
2022-07-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/jvi.00608-22 Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells. Aicher SM, Streicher F, Chazal M, Planas D, Luo D, Buchrieser J, Nemcova M, Seidlova V, Zukal J, Serra-Cobo J, Pontier D, Pain B, Zimmer G, Schwartz O, Roingeard P, Pikula J, Dacheux L, Jouvenet N. J Virol. 2022; 96 (14)
Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics.
Singh AV, Katz A, Maharajan RS, Gadicherla AK, [...], Luch A.
Sci Total Environ. 2022;
DOI: 10.1016/j.scitotenv.2022.160503
Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 μm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.
2022-11-25 2022 other Journal Article abstract-available 10.1016/j.scitotenv.2022.160503 Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics. Singh AV, Katz A, Maharajan RS, Gadicherla AK, Richter M, Heyda J, Del Pino P, Laux P, Luch A. Sci Total Environ. 2022;
Environmental contributions to the interactions of COVID-19 and asthma: A secondary publication and update.
Urrutia-Pereira M, Chong-Neto HJ, Annesi Maesano I, Ansotegui IJ, [...], D'Amato G.
World Allergy Organ J. 2022; 15 (9)
DOI: 10.1016/j.waojou.2022.100686
An outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19, especially for those with severe disease or non-allergic phenotypes, deserves further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations, and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, an earlier start and extension of the pollinating season, and the increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable of persisting in the environment and can be transported by bioaerosols which can further influence its transmission rate and seasonality. The COVID-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns and loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.waojou.2022.100686 Environmental contributions to the interactions of COVID-19 and asthma: A secondary publication and update. Urrutia-Pereira M, Chong-Neto HJ, Annesi Maesano I, Ansotegui IJ, Caraballo L, Cecchi L, Galán C, López JF, Aguttes MM, Peden D, Pomés A, Zakzuk J, Rosário Filho NA, D'Amato G. World Allergy Organ J. 2022; 15 (9)
Functional consequences of SARS-CoV-2 infection in pregnant women, fetoplacental unit, and neonate.
Carvajal J, Casanello P, Toso A, Farías M, [...], Sobrevia L.
Biochim Biophys Acta Mol Basis Dis. 2023; 1869 (1)
DOI: 10.1016/j.bbadis.2022.166582
The SARS-CoV-2 infection causes COVID-19 disease, characterized by acute respiratory distress syndrome, bilateral pneumonia, and organ failure. The consequences of maternal SARS-CoV-2 infection for the pregnant woman, fetus, and neonate are controversial. Thus, it is required to determine whether there is viral and non-viral vertical transmission in COVID-19. The disease caused by SARS-CoV-2 leads to functional alterations in asymptomatic and symptomatic pregnant women, the fetoplacental unit and the neonate. Several diseases of pregnancy, including COVID-19, affect the fetoplacental function, which causes in utero programming for young and adult diseases. A generalized inflammatory state and a higher risk of infection are seen in pregnant women with COVID-19. Obesity, diabetes mellitus, and hypertension may increase the vulnerability of pregnant women to infection by SARS-CoV-2. Alpha, Delta, and Omicron variants of SARS-CoV-2 show specific mutations that seem to increase the capacity of the virus to infect the pregnant woman, likely due to increasing its interaction via the virus S protein and angiotensin-converting enzyme 2 receptors. This review shows the literature addressing to what extent COVID-19 in pregnancy affects the pregnant woman, fetoplacental unit, and neonate. Prospective studies that are key in managing SARS-CoV-2 infection in pregnancy are discussed.
2022-10-20 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.bbadis.2022.166582 Functional consequences of SARS-CoV-2 infection in pregnant women, fetoplacental unit, and neonate. Carvajal J, Casanello P, Toso A, Farías M, Carrasco-Negue K, Araujo K, Valero P, Fuenzalida J, Solari C, Sobrevia L. Biochim Biophys Acta Mol Basis Dis. 2023; 1869 (1)
Clinical grade ACE2 effectively inhibits SARS-CoV-2 Omicron infections
Monteil V, Stephanie D, Klingström J, Thålin C, [...], Mirazimi A.
bioRxiv; 2021.
DOI: 10.1101/2021.12.25.474113
The recent emergence of the SARS-CoV-2 variant Omicron has caused considerable concern due to reduced vaccine efficacy and escape from neutralizing antibody therapeutics. Omicron is spreading rapidly around the globe and is suspected to account for most new COVID-19 cases in several countries, though the severity of Omicron-mediated disease is still under debate. It is therefore paramount to identify therapeutic strategies that inhibit the Omicron SARS-CoV-2 variant. Here we report using 3D structural modelling that Spike of Omicron can still associate with human ACE2. Sera collected after the second mRNA-vaccination did not exhibit a protective effect against Omicron while strongly neutralizing infection of VeroE6 cells with the reference Wuhan strain, confirming recent data by other groups on limited vaccine and convalescent sera neutralization efficacy against Omicron. Importantly, clinical grade recombinant human soluble ACE2, a drug candidate currently in clinical development, potently neutralized Omicron infection of VeroE6 cells with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. These data show that SARS-CoV-2 variant Omicron can be readily inhibited by soluble ACE2, providing proof of principle of a viable and effective therapeutic approach against Omicron infections.
2021-12-27 2021 other Preprint abstract-available 10.1101/2021.12.25.474113 Clinical grade ACE2 effectively inhibits SARS-CoV-2 Omicron infections Monteil V, Stephanie D, Klingström J, Thålin C, Kellner MJ, Christ W, Havervall S, Mereiter S, Knapp S, Montserrat N, Braunsfeld B, Kozieradzki I, Ali OH, Hagelkruys A, Stadlmann J, Oostenbrink C, Wirnsberger G, Penninger JM, Mirazimi A. bioRxiv; 2021.
SARS-CoV-2 Transmission by Arthropod Vectors: A Scoping Review.
Nekoei S, Khamesipour F, Benchimol M, Bueno-Marí R, [...], Ommi D.
Biomed Res Int. 2022; 2022
DOI: 10.1155/2022/4329423
COVID-19 is a respiratory disease of worldwide importance as it has brought enormous health problems to the world's population. The best-known way of transmission of the virus is through aerosolization. However, research is needed to explore other transmission routes. Researchers hypothesized that arthropods could transmit SARs-CoV-2. This study is aimed at reviewing research on arthropods as possible reservoirs and/or vectors of SARS-CoV-2, the causative agent of COVID-19. Following PRISMA guidelines, we conducted a systematic review using several electronic databases/academic searches with the search terms "arthropods," "coronavirus," and "transmission." A total of 64 unique articles were identified, of which 58 were included in the review. The SARS-CoV-2 virus is tiny and invisible to the naked eye, and its presence in stools, droplets, and surfaces was detected. One doubt is whether insects can transmit the virus from one place to another. Thus, a healthy carrier of the COVID-19 virus can be at the root of the contamination of their community or their family through the transport of the virus by insects from the interior (flies, cockroaches, etc.) from their feces and food surfaces. Hygiene care within communities and families becomes a prime factor. Coronavirus infection is a significant public health problem around the world. The prevention and control of outbreaks remain very important, even with the production of new vaccines. The main option to achieve this is the proper management of the transmission of the virus. The registry of infected people is currently the basis for the transmission of COVID-19. However, questions about the possibility of infection from other sources and its prevention are not receiving adequate attention. Numerous studies have shown the possibility that SARS-COV-2 fragments could have a longer life than shed respiratory droplets. Also, this virus is larger than those of other coronavirus families.
2022-08-08 2022 other Systematic Review; review-article; Review; Journal Article abstract-available 10.1155/2022/4329423 SARS-CoV-2 Transmission by Arthropod Vectors: A Scoping Review. Nekoei S, Khamesipour F, Benchimol M, Bueno-Marí R, Ommi D. Biomed Res Int. 2022; 2022
Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine.
Bru S, González-Marrón A, Lidón-Moyano C, Carballar R, [...], Martínez-Sánchez JM.
Environ Res. 2023; 216 (Pt 1)
DOI: 10.1016/j.envres.2022.114443

Introduction

The Angiotensin-Converting Enzyme 2 (ACE2) is the main receptor of the SARS-CoV-2. There is contradictory evidence on how the exposure to nicotine may module the concentration of soluble ACE2 (sACE2). The aim of this study was to assess the association between nicotine and sACE2 concentrations in saliva samples.

Methods

Pooled analysis performed with data retrieved from two studies (n = 634 and n = 302). Geometric mean (GM) concentrations of sACE2, both total and relative to the total amount of protein in the sample, were compared according to sociodemographic variables and variables associated to nicotine. Multivariable linear regression models were fitted to explore the associations of sACE2 with nicotine adjusting for sex, age and body mass index. Spearman's rank-correlation coefficients were estimated between the concentrations of nicotine and cotinine, and pack-years, the concentration of relative sACE2 and the isoforms of sACE2.

Results

We observed a significant increase of 0.108‰ and 0.087 ng/μl in the relative and absolute salivary sACE2 GM concentrations, respectively, between the lowest and highest nicotine levels. Similar results were observed for cotinine. These associations did not change in the multivariable linear models. There was a low correlation of nicotine and cotinine concentration with the concentration of relative salivary sACE2 (rs = 0.153 and rs = 0.132, respectively), pack-years (rs = 0.222 and rs = 0.235, respectively) and with the concentration of isoform 40 KDa (rs = 0.193 and rs = 0.140, respectively).

Conclusion

Salivary nicotine concentration seems to be limitedly associated with the concentration of sACE2.
2022-10-03 2022 other research-article; Journal Article abstract-available 10.1016/j.envres.2022.114443 Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine. Bru S, González-Marrón A, Lidón-Moyano C, Carballar R, Martínez-Láinez JM, Pérez-Martín H, Fu M, Pérez-Ortuño R, Ballbè M, Pascual JA, Fernández E, Clotet J, Martínez-Sánchez JM. Environ Res. 2023; 216 (Pt 1)
Smell and Taste Dysfunction in Pediatric Patients With SARS-CoV-2 Infection.
Púa Torrejón RC, Ordoño Saiz MV, González Alguacil E, Furones García M, [...], Soto Insuga V.
Pediatr Neurol. 2022; 136
DOI: 10.1016/j.pediatrneurol.2022.07.006

Introduction

Anosmia and hypogeusia are frequent symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults, but their incidence in children is unknown.

Objective

Describe the incidence and associated characteristics of olfactory and gustatory dysfunction in children with SARS-CoV-2 infection.

Material and methods

Descriptive study carried out by telephone survey of patients aged between five and 18 years with SARS-CoV-2 infection confirmed between March and December, 2020.

Results

Two hundred eighty Spanish patients (female: 42.2%) with a mean age of 10.4 years (±3.54, range: 5 to 17) were analyzed, 22.5% with other diseases (mostly respiratory: 11.8%). The most frequent symptoms were fever (55.36%) and neurological symptoms (45.7%). Forty-four (15.7%) were hospitalized due to the infection, in intensive care unit (ICU): 7.1%. Forty-five patients (16.1%) had anosmia and/or hypogeusia: 32 both, eight with hypogeusia only, and five with exclusively anosmia. The mean symptom duration in days for anosmia was 36.4, and for hypogeusia it was 27.6. Either symptom was the initial manifestation in 15 patients. None had anosmia/hypogeusia with no other symptoms. Anosmia/hypogeusia was related to the presence of respiratory infection, gastroenteritis, chills, odynophagia, myalgia, asthenia, and anorexia, but not severity (hospitalization/ICU admission). Cohabitation with another infected individual was associated with a higher incidence of anosmia/hypogeusia (P = 0.041) and duration of anosmia (P = 0.006). The presence of anosmia/hypogeusia in cohabitants was associated with longer duration of anosmia (P < 0.001).

Conclusions

The incidence of anosmia/hypogeusia in children with SARS-CoV-2 was lower than that reported in adults, although with a longer duration. Although no association was found between anosmia/hypogeusia and greater disease severity, recognition of these symptoms could help identify paucisymptomatic patients.
2022-08-01 2022 other research-article; Journal Article abstract-available 10.1016/j.pediatrneurol.2022.07.006 Smell and Taste Dysfunction in Pediatric Patients With SARS-CoV-2 Infection. Púa Torrejón RC, Ordoño Saiz MV, González Alguacil E, Furones García M, Cantarín Extremera V, Ruiz Falcó ML, Soto Insuga V. Pediatr Neurol. 2022; 136
Reactive ileal lymphoid hyperplasia related to SARS-CoV-2 infection as a unique clinical feature resembling Crohn's disease.
Qanneta R, Feliu-Masgoret M, García-Pardo G, Marimon-Cortés F.
Rev Gastroenterol Mex (Engl Ed). 2022;
DOI: 10.1016/j.rgmxen.2022.07.010
2022-07-21 2022 other Case Reports; case-report 10.1016/j.rgmxen.2022.07.010 Reactive ileal lymphoid hyperplasia related to SARS-CoV-2 infection as a unique clinical feature resembling Crohn's disease. Qanneta R, Feliu-Masgoret M, García-Pardo G, Marimon-Cortés F. Rev Gastroenterol Mex (Engl Ed). 2022;
Diet-Induced Obesity and NASH Impair Disease Recovery in SARS-CoV-2-Infected Golden Hamsters.
Briand F, Sencio V, Robil C, Heumel S, [...], Trottein F.
Viruses. 2022; 14 (9)
DOI: 10.3390/v14092067
Obese patients with non-alcoholic steatohepatitis (NASH) are prone to severe forms of COVID-19. There is an urgent need for new treatments that lower the severity of COVID-19 in this vulnerable population. To better replicate the human context, we set up a diet-induced model of obesity associated with dyslipidemia and NASH in the golden hamster (known to be a relevant preclinical model of COVID-19). A 20-week, free-choice diet induces obesity, dyslipidemia, and NASH (liver inflammation and fibrosis) in golden hamsters. Obese NASH hamsters have higher blood and pulmonary levels of inflammatory cytokines. In the early stages of a SARS-CoV-2 infection, the lung viral load and inflammation levels were similar in lean hamsters and obese NASH hamsters. However, obese NASH hamsters showed worse recovery (i.e., less resolution of lung inflammation 10 days post-infection (dpi) and lower body weight recovery on dpi 25). Obese NASH hamsters also exhibited higher levels of pulmonary fibrosis on dpi 25. Unlike lean animals, obese NASH hamsters infected with SARS-CoV-2 presented long-lasting dyslipidemia and systemic inflammation. Relative to lean controls, obese NASH hamsters had lower serum levels of angiotensin-converting enzyme 2 activity and higher serum levels of angiotensin II-a component known to favor inflammation and fibrosis. Even though the SARS-CoV-2 infection resulted in early weight loss and incomplete body weight recovery, obese NASH hamsters showed sustained liver steatosis, inflammation, hepatocyte ballooning, and marked liver fibrosis on dpi 25. We conclude that diet-induced obesity and NASH impair disease recovery in SARS-CoV-2-infected hamsters. This model might be of value for characterizing the pathophysiologic mechanisms of COVID-19 and evaluating the efficacy of treatments for the severe forms of COVID-19 observed in obese patients with NASH.
2022-09-17 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v14092067 Diet-Induced Obesity and NASH Impair Disease Recovery in SARS-CoV-2-Infected Golden Hamsters. Briand F, Sencio V, Robil C, Heumel S, Deruyter L, Machelart A, Barthelemy J, Bogard G, Hoffmann E, Infanti F, Domenig O, Chabrat A, Richard V, Prévot V, Nogueiras R, Wolowczuk I, Pinet F, Sulpice T, Trottein F. Viruses. 2022; 14 (9)
Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants.
Simões RSQ, Rodríguez-Lázaro D.
Int J Environ Res Public Health. 2022; 19 (4)
DOI: 10.3390/ijerph19042392
Several coronaviruses (CoVs) have been identified as human pathogens, including the α-CoVs strains HCoV-229E and HCoV-NL63 and the β-CoVs strains HCoV-HKU1 and HCoV-OC43. SARS-CoV, MERS-CoV, and SARS-CoV-2 are also classified as β-coronavirus. New SARS-CoV-2 spike genomic variants are responsible for human-to-human and interspecies transmissibility, consequences of adaptations of strains from animals to humans. The receptor-binding domain (RBD) of SARS-CoV-2 binds to receptor ACE2 in humans and animal species with high affinity, suggesting there have been adaptive genomic variants. New genomic variants including the incorporation, replacement, or deletion of the amino acids at a variety of positions in the S protein have been documented and are associated with the emergence of new strains adapted to different hosts. Interactions between mutated residues and RBD have been demonstrated by structural modelling of variants including D614G, B.1.1.7, B1.351, P.1, P2; other genomic variants allow escape from antibodies generated by vaccines. Epidemiological and molecular tools are being used for real-time tracking of pathogen evolution and particularly new SARS-CoV-2 variants. COVID-19 vaccines obtained from classical and next-generation vaccine production platforms have entered clinicals trials. Biotechnology strategies of the first generation (attenuated and inactivated virus-CoronaVac, CoVaxin; BBIBP-CorV), second generation (replicating-incompetent vector vaccines-ChAdOx-1; Ad5-nCoV; Sputnik V; JNJ-78436735 vaccine-replicating-competent vector, protein subunits, virus-like particles-NVX-CoV2373 vaccine), and third generation (nucleic-acid vaccines-INO-4800 (DNA); mRNA-1273 and BNT 162b (RNA vaccines) have been used. Additionally, dendritic cells (LV-SMENP-DC) and artificial antigen-presenting (aAPC) cells modified with lentiviral vector have also been developed to inhibit viral activity. Recombinant vaccines against COVID-19 are continuously being applied, and new clinical trials have been tested by interchangeability studies of viral vaccines developed by classical and next-generation platforms.
2022-02-18 2022 other review-article; Review; Journal Article abstract-available 10.3390/ijerph19042392 Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants. Simões RSQ, Rodríguez-Lázaro D. Int J Environ Res Public Health. 2022; 19 (4)
Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis.
Schmid B, Griesel M, Fischer AL, Romero CS, [...], Fichtner F.
J Clin Med. 2022; 11 (2)
DOI: 10.3390/jcm11020391
Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65-1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03-1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71-0.96) but may have little or no effect on mortality (RR: 1.08, 0.51-2.31). Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available 10.3390/jcm11020391 Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis. Schmid B, Griesel M, Fischer AL, Romero CS, Metzendorf MI, Weibel S, Fichtner F. J Clin Med. 2022; 11 (2)
Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity.
Batlle D, Monteil V, Garreta E, Hassler L, [...], Penninger JM.
Cell. 2022; 185 (11)
DOI: 10.1016/j.cell.2022.05.004
2022-05-01 2022 other Letter; Comment; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural 10.1016/j.cell.2022.05.004 Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity. Batlle D, Monteil V, Garreta E, Hassler L, Wysocki J, Chandar V, Schwartz RE, Mirazimi A, Montserrat N, Bader M, Penninger JM. Cell. 2022; 185 (11)
SARS-CoV-2, fertility and assisted reproduction.
Ata B, Vermeulen N, Mocanu E, Gianaroli L, [...], Veiga A.
Hum Reprod Update. 2022;
DOI: 10.1093/humupd/dmac037

Background

In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain.

Objective and rationale

This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals.

Search methods

PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible.

Outcomes

From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients.

Wider implications

This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.
2022-11-14 2022 other Journal Article abstract-available 10.1093/humupd/dmac037 SARS-CoV-2, fertility and assisted reproduction. Ata B, Vermeulen N, Mocanu E, Gianaroli L, Lundin K, Rautakallio-Hokkanen S, Tapanainen JS, Veiga A. Hum Reprod Update. 2022;
Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19.
Yang F, Jiang XL, Tariq A, Sadia S, [...], Bussmann RW.
J Integr Med. 2022; 20 (6)
DOI: 10.1016/j.joim.2022.08.001
At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2-44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflav1in-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4-43.8 μmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.
2022-08-09 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.joim.2022.08.001 Potential medicinal plants involved in inhibiting 3CL<sup>pro</sup> activity: A practical alternate approach to combating COVID-19. Yang F, Jiang XL, Tariq A, Sadia S, Ahmed Z, Sardans J, Aleem M, Ullah R, Bussmann RW. J Integr Med. 2022; 20 (6)
Nature of viruses and pandemics: Coronaviruses.
Enjuanes L, Sola I, Zúñiga S, Honrubia JM, [...], Ripoll-Gómez J.
Curr Res Immunol. 2022; 3
DOI: 10.1016/j.crimmu.2022.08.003
Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.crimmu.2022.08.003 Nature of viruses and pandemics: Coronaviruses. Enjuanes L, Sola I, Zúñiga S, Honrubia JM, Bello-Pérez M, Sanz-Bravo A, González-Miranda E, Hurtado-Tamayo J, Requena-Platek R, Wang L, Muñoz-Santos D, Sánchez CM, Esteban A, Ripoll-Gómez J. Curr Res Immunol. 2022; 3
Development of Neuropathic Post-COVID Pain Symptoms Is Not Associated with Serological Biomarkers at Hospital Admission in COVID-19 Survivors: A Secondary Analysis.
Fernández-de-Las-Peñas C, Herrero-Montes M, Ferrer-Pargada D, Izquierdo-Cuervo S, [...], Parás-Bravo P.
Pain Med. 2022; 23 (12)
DOI: 10.1093/pm/pnac086
2022-12-01 2022 other letter; Journal Article 10.1093/pm/pnac086 Development of Neuropathic Post-COVID Pain Symptoms Is Not Associated with Serological Biomarkers at Hospital Admission in COVID-19 Survivors: A Secondary Analysis. Fernández-de-Las-Peñas C, Herrero-Montes M, Ferrer-Pargada D, Izquierdo-Cuervo S, Palacios-Ceña D, Arendt-Nielsen L, Torres-Macho J, Parás-Bravo P. Pain Med. 2022; 23 (12)
Evaluation of five immunoassays and one lateral flow immunochromatography for anti-SARS-CoV-2 antibodies detection.
Montolio Breva S, Molina Clavero C, Gómez Bertomeu F, Picó-Plana E, [...], Sans-Mateu MT.
Enferm Infecc Microbiol Clin (Engl Ed). 2022; 40 (9)
DOI: 10.1016/j.eimce.2020.12.007

Introduction

In order to deal with the current pandemic caused by the novel SARS-CoV-2 coronavirus several serological immunoassays have been recently developed with the objective of being used as a complementary diagnostic tool and to support the RT-PCR technique currently considered the "gold-standard" method. However, these new assays need to be evaluated and validated. The purpose of this study was to assess the performance of five immunoassays (two ELISA and three CLIA assays) and one rapid immunochromatographic test for the detection of anti-SARS-CoV-2 antibodies.

Methods

Five semiquantitative immunoassays (MENARINI®, PALEX®, VIRCLIA®, ROCHE® and SIEMENS®) and one lateral flow rapid test (WONDFO®) were performed. A total of 124 samples were studied. Case serum samples (n=78) were obtained from COVID-19 patients confirmed by real-time RT-PCR/epidemiological-clinical-radiological criteria, and control non-SARS-CoV-2 samples (n=46) belonged to healthy healthcare workers involved in a seroprevalence study.

Results

Overall, the tests showed sensitivities around 70-90% and specificities greater than 95%, including the immunochromatographic test. In addition, we observed very good agreements among them, being better for the detection of IgG than for IgM antibodies (Cohen's kappa index of 0.95 for VIRCLIA® IgG with ROCHE®), as well as good diagnostic power of the tests as determined by the ROC curves.

Conclusions

This study demonstrates the proper performance of the different immunoassays in order to be applied in the clinical practice as support in the diagnostic approach and in the development of vaccines and seroepidemiological studies of COVID-19.
2022-11-01 2022 other research-article; Journal Article abstract-available 10.1016/j.eimce.2020.12.007 Evaluation of five immunoassays and one lateral flow immunochromatography for anti-SARS-CoV-2 antibodies detection. Montolio Breva S, Molina Clavero C, Gómez Bertomeu F, Picó-Plana E, Serrat Orús N, Palau Sánchez I, Mestre-Prad MT, Sans-Mateu MT. Enferm Infecc Microbiol Clin (Engl Ed). 2022; 40 (9)
Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?
Menasria T, Aguilera M.
Microorganisms. 2022; 10 (2)
DOI: 10.3390/microorganisms10020467
Here, we report a first comprehensive genomic analysis of SARS-CoV-2 variants circulating in North African countries, including Algeria, Egypt, Libya, Morocco, Sudan and Tunisia, with respect to genomic clades and mutational patterns. As of December 2021, a total of 1669 high-coverage whole-genome sequences submitted to EpiCoV GISAID database were analyzed to infer clades and mutation annotation compared with the wild-type variant Wuhan-Hu-1. Phylogenetic analysis of SARS-CoV-2 genomes revealed the existence of eleven GISAID clades with GR (variant of the spike protein S-D614G and nucleocapsid protein N-G204R), GH (variant of the ORF3a coding protein ORF3a-Q57H) and GK (variant S-T478K) being the most common with 25.9%, 19.9%, and 19.6%, respectively, followed by their parent clade G (variant S-D614G) (10.3%). Lower prevalence was noted for GRY (variant S-N501Y) (5.1%), S (variant ORF8-L84S) (3.1%) and GV (variant of the ORF3a coding protein NS3-G251V) (2.0%). Interestingly, 1.5% of total genomes were assigned as GRA (Omicron), the newly emerged clade. Across the North African countries, 108 SARS-CoV-2 lineages using the Pangolin assignment were identified, whereby most genomes fell within six major lineages and variants of concern (VOC) including B.1, the Delta variants (AY.X, B.1.617.2), C.36, B.1.1.7 and B.1.1. The effect of mutations in SAR-CoV-2 genomes highlighted similar profiles with D614G spike (S) and ORF1b-P314L variants as the most changes found in 95.3% and 87.9% of total sequences, respectively. In addition, mutations affecting other viral proteins appeared frequently including; N:RG203KR, N:G212V, NSP3:T428I, ORF3a:Q57H, S:N501Y, M:I82T and E:V5F. These findings highlight the importance of genomic surveillance for understanding the SARS-CoV-2 genetic diversity and its spread patterns, leading to a better guiding of public health intervention measures. The know-how analysis of the present work could be implemented worldwide in order to overcome this health crisis through harmonized approaches.
2022-02-18 2022 other research-article; Journal Article abstract-available 10.3390/microorganisms10020467 Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect? Menasria T, Aguilera M. Microorganisms. 2022; 10 (2)
Eccentric Training in Pulmonary Rehabilitation of Post-COVID-19 Patients: An Alternative for Improving the Functional Capacity, Inflammation, and Oxidative Stress.
Contreras-Briceño F, Espinosa-Ramírez M, Rozenberg D, Reid WD.
Biology (Basel). 2022; 11 (10)
DOI: 10.3390/biology11101446
The purpose of this narrative review is to highlight the oxidative stress induced in COVID-19 patients (SARS-CoV-2 infection), describe longstanding functional impairments, and provide the pathophysiologic rationale that supports aerobic eccentric (ECC) exercise as a novel alternative to conventional concentric (CONC) exercise for post-COVID-19 patients. Patients who recovered from moderate-to-severe COVID-19 respiratory distress demonstrate long-term functional impairment. During the acute phase, SARS-CoV-2 induces the generation of reactive oxygen species that can be amplified to a "cytokine storm". The resultant inflammatory and oxidative stress process causes organ damage, particularly in the respiratory system, with the lungs as the tissues most susceptible to injury. The acute illness often requires a long-term hospital stay and consequent sarcopenia. Upon discharge, muscle weakness compounded by limited lung and cardiac function is often accompanied by dyspnea, myalgia, anxiety, depression, and sleep disturbance. Consequently, these patients could benefit from pulmonary rehabilitation (PR), with exercise as a critical intervention (including sessions of strength and endurance or aerobic exercises). Unfortunately, conventional CONC exercises induce significant cardiopulmonary stress and increase inflammatory and oxidative stress (OS) when performed at moderate/high intensity, which can exacerbate debilitating dyspnoea and muscle fatigue post-COVID-19. Eccentric training (ECC) is a well-tolerated alternative that improves muscle mass while mitigating cardiopulmonary stress in patients with COPD and other chronic diseases. Similar benefits could be realized in post-COVID-19 patients. Consequently, these patients could benefit from PR with exercise as a critical intervention.
2022-10-01 2022 other review-article; Review; Journal Article abstract-available 10.3390/biology11101446 Eccentric Training in Pulmonary Rehabilitation of Post-COVID-19 Patients: An Alternative for Improving the Functional Capacity, Inflammation, and Oxidative Stress. Contreras-Briceño F, Espinosa-Ramírez M, Rozenberg D, Reid WD. Biology (Basel). 2022; 11 (10)
Persistent COVID-19 syndrome. A narrative review.
López-Sampalo A, Bernal-López MR, Gómez-Huelgas R.
Rev Clin Esp (Barc). 2022; 222 (4)
DOI: 10.1016/j.rceng.2021.10.001
As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.
2022-02-28 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.rceng.2021.10.001 Persistent COVID-19 syndrome. A narrative review. López-Sampalo A, Bernal-López MR, Gómez-Huelgas R. Rev Clin Esp (Barc). 2022; 222 (4)
ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19.
Maza MDC, Úbeda M, Delgado P, Horndler L, [...], Fresno M.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.836516

Background

COVID-19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.

Methods

We analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein.

Results

We found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms.

Conclusions

These findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.
2022-03-23 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.836516 ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19. Maza MDC, Úbeda M, Delgado P, Horndler L, Llamas MA, van Santen HM, Alarcón B, Abia D, García-Bermejo L, Serrano-Villar S, Bastolla U, Fresno M. Front Immunol. 2022; 13
Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin 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. 2022; 225 (6)
DOI: 10.1093/infdis/jiab540

Background

Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need.

Methods

Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and 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 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) 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.
2022-03-01 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/infdis/jiab540 Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin 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. 2022; 225 (6)
What Should Be Learned From Repurposed Antivirals Against SARS-CoV-2?
Martinez MA.
Front Microbiol. 2022; 13
DOI: 10.3389/fmicb.2022.843587
2022-02-16 2022 other discussion; Journal Article 10.3389/fmicb.2022.843587 What Should Be Learned From Repurposed Antivirals Against SARS-CoV-2? Martinez MA. Front Microbiol. 2022; 13
Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernández-Pato A, Virseda-Berdices A, Resino S, Ryan P, [...], Fernández-Rodríguez A.
Emerg Microbes Infect. 2022; 11 (1)
DOI: 10.1080/22221751.2022.2038021

Background

MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival.

Methods and results

Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042).

Conclusions

SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.
2022-12-01 2022 fondo-covid research-article; Journal Article abstract-available 10.1080/22221751.2022.2038021 Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Fernández-Pato A, Virseda-Berdices A, Resino S, Ryan P, Martínez-González O, Pérez-García F, Martin-Vicente M, Valle-Millares D, Brochado-Kith O, Blancas R, Martínez A, Ceballos FC, Bartolome-Sánchez S, Vidal-Alcántara EJ, Alonso D, Blanca-López N, Ramirez Martinez-Acitores I, Martin-Pedraza L, Jiménez-Sousa MÁ, Fernández-Rodríguez A. Emerg Microbes Infect. 2022; 11 (1)
Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in.
Pugliatti M, Hartung HP, Oreja-Guevara C, Pozzilli C, [...], Berger T.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.1045101
It has been over a year since people with multiple sclerosis (pwMS) have been receiving vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a negligible number of cases in which vaccination led to a relapse or new onset MS, experts around the world agree that the potential consequences of COVID-19 in pwMS by far outweigh the risks of vaccination. This article reviews the currently available types of anti-SARS-CoV-2 vaccines and the immune responses they elicit in pwMS treated with different DMTs. Findings to date highlight the importance of vaccine timing in relation to DMT dosing to maximize protection, and of encouraging pwMS to get booster doses when offered.
2022-10-17 2022 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2022.1045101 Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in. Pugliatti M, Hartung HP, Oreja-Guevara C, Pozzilli C, Airas L, Alkhawajah M, Grigoriadis N, Magyari M, Van Wijmeersch B, Zakaria M, Linker R, Chan A, Vermersch P, Berger T. Front Immunol. 2022; 13
Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.
Fico G, Isayeva U, De Prisco M, Oliva V, [...], Murru A.
Eur Neuropsychopharmacol. 2022; 66
DOI: 10.1016/j.euroneuro.2022.10.004
Several psychotropic drugs, including antidepressants (AD), mood stabilizers, and antipsychotics (AP) have been suggested to have favorable effects in the treatment of COVID-19. The aim of this systematic review and meta-analysis was to collect evidence from studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Two independent authors searched PubMed-MEDLINE, Scopus, PsycINFO, and ClinicalTrials.gov databases, and reviewed the reference lists of articles for eligible articles published up to 13th December 2021. All computational, preclinical and clinical (observational and/or RCTs) studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were considered for inclusion. We conducted random effect meta-analyses on clinical studies reporting the effect of AD or AP on COVID-19 outcomes. 29 studies were included in the synthesis: 15 clinical, 9 preclinical, and 5 computational studies. 9 clinical studies could be included in the quantitative analyses. AD did not increase the risk of severe COVID-19 (RR= 1.71; CI 0.65-4.51) or mortality (RR=0.94; CI 0.81-1.09). Fluvoxamine was associated with a reduced risk of mortality for COVID-19 (OR=0.15; CI 0.02-0.95). AP increased the risk of severe COVID-19 (RR=3.66; CI 2.76-4.85) and mortality (OR=1.53; CI 1.15-2.03). Fluvoxamine might be a possible candidate for psychotropic drug repurposing in COVID-19 due to its anti-inflammatory and antiviral potential, while evidence on other AD is still controversial. Although AP are associated with worse COVID-19 outcomes, their use should be evaluated case to case and ongoing treatment with antipsychotics should be not discontinued in psychiatric patients.
2022-10-20 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.euroneuro.2022.10.004 Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis. Fico G, Isayeva U, De Prisco M, Oliva V, Solè B, Montejo L, Grande I, Arbelo N, Gomez-Ramiro M, Pintor L, Carpiniello B, Manchia M, Vieta E, Murru A. Eur Neuropsychopharmacol. 2022; 66
Heterologous Systemic Prime-Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters.
Katsande PM, Fernández-Bastit L, Ferreira WT, Vergara-Alert J, [...], Cutting SM.
Vaccines (Basel). 2022; 10 (11)
DOI: 10.3390/vaccines10111900
Background: Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are administered systemically and typically result in poor immunogenicity at the mucosa. As a result, vaccination is unable to reduce viral shedding and transmission, ultimately failing to prevent infection. One possible solution is that of boosting a systemic vaccine via the nasal route resulting in mucosal immunity. Here, we have evaluated the potential of bacterial spores as an intranasal boost. Method: Spores engineered to express SARS-CoV-2 antigens were administered as an intranasal boost following a prime with either recombinant Spike protein or the Oxford AZD1222 vaccine. Results: In mice, intranasal boosting following a prime of either Spike or vaccine produced antigen-specific sIgA at the mucosa together with the increased production of Th1 and Th2 cytokines. In a hamster model of infection, the clinical and virological outcomes resulting from a SARS-CoV-2 challenge were ameliorated. Wuhan-specific sIgA were shown to cross-react with Omicron antigens, suggesting that this strategy might offer protection against SARS-CoV-2 variants of concern. Conclusions: Despite being a genetically modified organism, the spore vaccine platform is attractive since it offers biological containment, the rapid and cost-efficient production of vaccines together with heat stability. As such, employed in a heterologous systemic prime-mucosal boost regimen, spore vaccines might have utility for current and future emerging diseases.
2022-11-10 2022 other research-article; Journal Article abstract-available 10.3390/vaccines10111900 Heterologous Systemic Prime-Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters. Katsande PM, Fernández-Bastit L, Ferreira WT, Vergara-Alert J, Hess M, Lloyd-Jones K, Hong HA, Segales J, Cutting SM. Vaccines (Basel). 2022; 10 (11)
Revealing druggable cryptic pockets in the Nsp1 of SARS-CoV-2 and other β-coronaviruses by simulations and crystallography.
Borsatto A, Akkad O, Galdadas I, Ma S, [...], Gervasio FL.
Elife. 2022; 11
DOI: 10.7554/elife.81167
Non-structural protein 1 (Nsp1) is a main pathogenicity factor of α- and β-coronaviruses. Nsp1 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suppresses the host gene expression by sterically blocking 40S host ribosomal subunits and promoting host mRNA degradation. This mechanism leads to the downregulation of the translation-mediated innate immune response in host cells, ultimately mediating the observed immune evasion capabilities of SARS-CoV-2. Here, by combining extensive molecular dynamics simulations, fragment screening and crystallography, we reveal druggable pockets in Nsp1. Structural and computational solvent mapping analyses indicate the partial crypticity of these newly discovered and druggable binding sites. The results of fragment-based screening via X-ray crystallography confirm the druggability of the major pocket of Nsp1. Finally, we show how the targeting of this pocket could disrupt the Nsp1-mRNA complex and open a novel avenue to design new inhibitors for other Nsp1s present in homologous β-coronaviruses.
2022-11-22 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.7554/elife.81167 Revealing druggable cryptic pockets in the Nsp1 of SARS-CoV-2 and other β-coronaviruses by simulations and crystallography. Borsatto A, Akkad O, Galdadas I, Ma S, Damfo S, Haider S, Kozielski F, Estarellas C, Gervasio FL. Elife. 2022; 11
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 IM; 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)
Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.
Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, [...], Martinez I.
Birth. 2022;
DOI: 10.1111/birt.12667

Introduction

Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later.

Methods

We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples.

Results

At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001).

Conclusions

High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.
2022-07-08 2022 other research-article; Journal Article abstract-available 10.1111/birt.12667 Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later. Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, Mas V, Vigil-Vázquez S, Vázquez M, Manzanares A, Cano O, Alonso R, Sepúlveda-Crespo D, Tarancón-Díez L, Muñoz-Fernández MÁ, Muñoz-Chapuli M, Resino S, Navarro ML, Martinez I. Birth. 2022;
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
Type 2 Diabetes Mellitus and COVID-19: A Narrative Review.
Rey-Reñones C, Martinez-Torres S, Martín-Luján FM, Pericas C, [...], Grau M.
Biomedicines. 2022; 10 (9)
DOI: 10.3390/biomedicines10092089
Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, some studies suggest a bidirectional interaction between T2DM and COVID-19. A growing body of evidence shows that COVID-19 prognosis in individuals with T2DM is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with T2DM after SARS-CoV-2 infection. The most common treatments for T2DM may influence SARS-CoV-2 and their implication in infection is briefly discussed in this review. A better understanding of the link between TD2M and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.
2022-08-26 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10092089 Type 2 Diabetes Mellitus and COVID-19: A Narrative Review. Rey-Reñones C, Martinez-Torres S, Martín-Luján FM, Pericas C, Redondo A, Vilaplana-Carnerero C, Dominguez A, Grau M. Biomedicines. 2022; 10 (9)
Overview of coronavirus pandemic
Artiga-Sainz L, Ibáñez-Navarro A, Morante-Ruiz M, Bilbao J, [...], Quintana-Díaz M.
Computational Approaches for Novel Therapeutic and Diagnostic Designing to Mitigate SARS-CoV-2 Infection. 2022;
DOI:
During the last months of 2019, numerous cases of respiratory illness such as pneumonia and acute respiratory distress syndrome were described in Wuhan, the capital city of Hubei province in China. At the same time, several research groups identified and reported the etiological agent, that included within the Coronaviridae family and the order Nidovirales, named SARS-CoV-2. Subsequently, the pathological and clinical status caused by the pathogen is commonly known as Coronavirus disease 2019 (COVID-19). In a short period, the outbreak of emerging spread across the world. Therefore the World Health Organization declared a public health emergency of international concern on January 30, 2020, and as a pandemic on March 11, 2020. Many different public health and epidemiological studies have been published since the COVID-19 outbreak, but fatality rates (those that relate the number of cases to mortality) are difficult to assess with certainty. Mean and median case-fatality rates worldwide are near to 3% and 2%, respectively. The median infection fatality calculated from serologic prevalence varies from 0.00% to 1.63% but is mostly estimated between 0.27% and 0.9%. These indexes are influenced by geographic location, socioeconomic status, sex, age, and health conditions, among others.
2022-01-01 2022 other chapter-article abstract-available Overview of coronavirus pandemic Artiga-Sainz L, Ibáñez-Navarro A, Morante-Ruiz M, Bilbao J, Rodríguez de Lema-Tapetado G, Sarria-Santamera A, Quintana-Díaz M. Computational Approaches for Novel Therapeutic and Diagnostic Designing to Mitigate SARS-CoV-2 Infection. 2022;
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)
The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes.
Mercado-Gómez M, Prieto-Fernández E, Goikoetxea-Usandizaga N, Vila-Vecilla L, [...], Martínez-Chantar ML.
Commun Biol. 2022; 5 (1)
DOI: 10.1038/s42003-022-03789-9
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2) and primary human hepatocytes. Pseudotyped viral particles expressing the full-length spike of SARS-CoV-2 and recombinant receptor binding domain (RBD) bind to ACE2 expressed by hepatocytes, promoting metabolic reprogramming towards glycolysis but also impaired mitochondrial activity. Human and hACE2 primary hepatocytes, where steatosis and inflammation were induced by methionine and choline deprivation, are more vulnerable to infection. Inhibition of the renin-angiotensin system increases the susceptibility of primary hepatocytes to infection with pseudotyped viral particles. Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes patients known to partially attenuate fatty liver, reduces the infection of human and hACE2 hepatocytes. In summary, we provide evidence that hepatocytes are amenable to infection with SARS-CoV-2 pseudovirus, and we propose that metformin could be a therapeutic option to attenuate infection by SARS-CoV-2 in patients with fatty liver.
2022-08-17 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s42003-022-03789-9 The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes. Mercado-Gómez M, Prieto-Fernández E, Goikoetxea-Usandizaga N, Vila-Vecilla L, Azkargorta M, Bravo M, Serrano-Maciá M, Egia-Mendikute L, Rodríguez-Agudo R, Lachiondo-Ortega S, Lee SY, Eguileor Giné A, Gil-Pitarch C, González-Recio I, Simón J, Petrov P, Jover R, Martínez-Cruz LA, Ereño-Orbea J, Delgado TC, Elortza F, Jiménez-Barbero J, Nogueiras R, Prevot V, Palazon A, Martínez-Chantar ML. Commun Biol. 2022; 5 (1)
Correlates with Vaccine Protective Capacity and COVID-19 Disease Symptoms Identified by Serum Proteomics in Vaccinated Individuals.
Villar M, Urra JM, Artigas-Jerónimo S, Mazuecos L, [...], de la Fuente J.
Molecules. 2022; 27 (18)
DOI: 10.3390/molecules27185933
In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
2022-09-13 2022 other research-article; Journal Article abstract-available 10.3390/molecules27185933 Correlates with Vaccine Protective Capacity and COVID-19 Disease Symptoms Identified by Serum Proteomics in Vaccinated Individuals. Villar M, Urra JM, Artigas-Jerónimo S, Mazuecos L, Contreras M, Vaz-Rodrigues R, Rodríguez-Del-Río FJ, Gortázar C, de la Fuente J. Molecules. 2022; 27 (18)
Endometrial gene expression differences in women with coronavirus disease 2019.
de Miguel-Gómez L, Sebastián-León P, Romeu M, Pellicer N, [...], Cervelló I.
Fertil Steril. 2022;
DOI: 10.1016/j.fertnstert.2022.09.013

Objective

To study the potential effect of coronavirus disease (COVID-19) on the endometrial transcriptome of affected, symptomatic women for the detection of altered gene expression.

Design

Pilot study of the endometrial transcriptomes of women manifesting COVID-19 compared with those of women without COVID-19 undergoing hysteroscopic procedures for benign gynecologic disorders using RNA sequencing.

Setting

Hospital and university laboratories.

Patient(s)

Women with (n = 14) and without a COVID-19 (n = 10) diagnosis based on a nasopharyngeal swab analysis using quantitative reverse-transcription polymerase chain reaction. The endometrium of the patients with COVID-19 had previously been tested for severe acute respiratory syndrome coronavirus 2 infection, revealing the absence of the virus in this tissue.

Intervention(s)

Endometrial biopsy sample collection.

Main outcomes measure(s)

Endometrial gene expression and functional analysis of symptomatic patients with COVID-19 vs. individuals without the infection.

Result(s)

The systemic disease COVID-19 altered endometrial gene expression in 75% of the women, with the patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, and BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, and IRF4) (false discovery rate<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in the endometria of the patients with COVID-19, including up-regulation in pathways involved in the development of immune responses to viruses and cytokine inflammation, reflecting elicitation of a COVID-19 response pathway.

Conclusion(s)

Coronavirus disease 2019 affects endometrial gene expression despite the absence of severe acute respiratory syndrome coronavirus 2 RNA in endometrial tissues.
2022-09-13 2022 other research-article; Journal Article abstract-available 10.1016/j.fertnstert.2022.09.013 Endometrial gene expression differences in women with coronavirus disease 2019. de Miguel-Gómez L, Sebastián-León P, Romeu M, Pellicer N, Faus A, Pellicer A, Díaz-Gimeno P, Cervelló I. Fertil Steril. 2022;
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)
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)
Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants.
Fernández-de-Las-Peñas C, Cuadrado ML, Gómez-Mayordomo V, Torres-Macho J, [...], Arendt-Nielsen L.
Headache. 2022; 62 (9)
DOI: 10.1111/head.14398

Objective

This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID-19) and as a post-COVID-19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

Headache can be present in up to 50% of individuals during the acute phase of SARS-CoV-2 infection and in 10% of subjects during the post-COVID-19 phase. There are no data on differences in the occurrence of headache in the acute- and post-COVID-19 phase according to the SARS-CoV-2 variants.

Methods

A cross-sectional cohort study was conducted. Unvaccinated subjects previously hospitalized for COVID-19 caused by the Wuhan (n = 201), Alpha (n = 211), or Delta (n = 202) SARS-CoV-2 variants were scheduled for a telephone interview 6 months after hospital discharge. Hospitalization data were collected from hospital medical records.

Results

The presence of headache as a COVID-19 onset symptom at hospitalization was higher in subjects with the Delta variant (66/202, 32.7%) than in those infected with the Wuhan (42/201, 20.9%; odds ratio [OR] 1.83, 95% confidence interval [CI] 1.17-2.88) or Alpha (25/211, 11.8%; OR 3.61, 95% CI, 2.16-6.01) variants. The prevalence of post-COVID-19 headache 6 months after hospital discharge was higher in individuals infected with the Delta variant (26/202, 12.9%) than in those infected with the Wuhan (11/201, 5.5%; OR 2.52, 95% CI 1.22-5.31) or Alpha (eight of 211, 3.8%; OR 3.74, 95% CI 1.65-8.49) variants. The presence of headache as a COVID-19 onset symptom was associated with post-COVID-19 headache in subjects infected with the Wuhan (OR 7.75, 95% CI 2.15-27.93) and Delta variants (OR 2.78, 95% CI 1.20-6.42) but not with the Alpha variant (OR 2.60, 95% CI 0.49-13.69).

Conclusion

Headache was a common symptom in both the acute- and post-COVID-19 phase in subjects infected with the Wuhan, Alpha, and Delta variants but mostly in those infected with the Delta variant.
2022-09-16 2022 other research-article; Journal Article abstract-available 10.1111/head.14398 Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants. Fernández-de-Las-Peñas C, Cuadrado ML, Gómez-Mayordomo V, Torres-Macho J, Pellicer-Valero OJ, Martín-Guerrero JD, Arendt-Nielsen L. Headache. 2022; 62 (9)
SARS-CoV-2 infection and liver involvement.
Luo M, Ballester MP, Soffientini U, Jalan R, [...], Mehta G.
Hepatol Int. 2022; 16 (4)
DOI: 10.1007/s12072-022-10364-1
The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless, the mechanism of liver injury in SARS-CoV-2 infection remains largely unknown. This review aims to provide an overview of the mechanisms by which SARS-CoV-2 induces liver injury, and the impact of COVID-19 on cirrhosis, alcohol-related liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, hepatitis B and C virus infection, liver-transplant recipients and patients with hepatocellular carcinoma. Finally, emerging data on vaccination in liver diseases is discussed, to help inform public health policy.
2022-06-29 2022 other review-article; Review; Journal Article abstract-available 10.1007/s12072-022-10364-1 SARS-CoV-2 infection and liver involvement. Luo M, Ballester MP, Soffientini U, Jalan R, Mehta G. Hepatol Int. 2022; 16 (4)
Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination.
Hernández-Luis P, Aguilar R, Pelegrin-Pérez J, Ruiz-Olalla G, [...], Engel P.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.816389
The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerging variants raises concerns about their capacity to evade immune protection provided by natural infection or vaccination. The receptor-binding domain (RBD) of the viral spike protein is the major target of neutralizing antibodies, and viral variants accumulate mutations in this region. In this study, we determined the antibody neutralization capacity against the RBD of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Epsilon (B.1.427), Kappa (B.1.617.1), and Delta (B.1.617.2) in a cohort of healthcare workers naturally infected or receiving COVID-19 mRNA vaccines from Moderna or Pfizer-BioNTech. We show that the five RBD variants displayed an augmented binding to ACE2 compared to the original Wuhan strain. The most significant increase was observed in variants Epsilon and Delta, containing mutation L452R. Using a flow cytometry cell-based assay, we found that SARS-CoV-2-infected subjects presented low levels of RBD-specific neutralizing antibodies against all variants analyzed, except Alpha. However, the neutralizing activity incremented considerably after a subsequent mRNA-vaccine dose, to levels significantly higher than those in naïve individuals receiving two vaccine doses. Importantly, we observed partially impaired neutralizing responses against most variants in fully vaccinated individuals. Variants Gamma and Kappa encompassing RBD E484K/Q mutations presented the highest neutralizing resistance. Furthermore, a wide heterogeneity in the magnitude of RBD-specific neutralizing responses against all tested SARS-CoV-2 variants following both mRNA vaccines was detected. Altogether, our findings provide important knowledge regarding SARS-CoV-2 vaccine-induced immunity, and should be very useful to guide future vaccination regimens and personalized vaccine approaches.
2022-04-06 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.816389 Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination. Hernández-Luis P, Aguilar R, Pelegrin-Pérez J, Ruiz-Olalla G, García-Basteiro AL, Tortajada M, Moncunill G, Dobaño C, Angulo A, Engel P. Front Immunol. 2022; 13
GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility.
Torrens-Mas M, Perelló-Reus CM, Trias-Ferrer N, Ibargüen-González L, [...], Gonzalez-Freire M.
Front Cell Infect Microbiol. 2022; 12
DOI: 10.3389/fcimb.2022.942951
Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.
2022-07-22 2022 other research-article; Journal Article abstract-available 10.3389/fcimb.2022.942951 GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility. Torrens-Mas M, Perelló-Reus CM, Trias-Ferrer N, Ibargüen-González L, Crespí C, Galmes-Panades AM, Navas-Enamorado C, Sanchez-Polo A, Piérola-Lopetegui J, Masmiquel L, Crespi LS, Barcelo C, Gonzalez-Freire M. Front Cell Infect Microbiol. 2022; 12
Study of the sensitivity and specificity of smell and taste disorders as a predictive factor of SARS-CoV-2 infection among primary care healthcare professionals: a retrospective observational study.
Ruiz-Comellas A, Roura Poch P, Sauch Valmaña G, Guadalupe-Fernández V, [...], Ramirez-Morros A.
BJGP Open. 2022; 6 (2)
DOI: 10.3399/bjgpo.2021.0141

Background

Among the manifestations of COVID-19 are taste and smell disorders (TSDs).

Aim

To evaluate the sensitivity and specificity of TSDs and other associated symptoms to estimate predictive values for determining SARS-CoV-2 infection.

Design & setting

A retrospective observational study of healthcare professionals in Catalonia, Spain.

Method

A study of the sensitivity and specificity of TSDs has been carried out using the polymerase chain reaction (PCR) test for the diagnosis of SARS-CoV-2 as the gold standard value. Logistic regressions adjusted for age and sex were performed to identify additional symptoms that might be associated with COVID-19.

Results

The results are based on 226 healthcare workers with clinical symptoms suggestive of COVID-19, 116 with positive PCR and 110 with negative PCR. TSDs had an odds ratio (OR) of 12.4 (95% confidence interval [CI] = 6.3 to 26.2), sensitivity 60.3% and specificity 89.1%. In the logistic regression model, the association of TSD, fever or low-grade fever, shivering, dyspnoea, arthralgia, and myalgia obtained an area under the curve (AUC) of 85.7% (95% CI = 80.7 % to 90.7 %), sensitivity 82.8 %, specificity 80.0%, and positive predictive values 81.4% and negative 81.5%.

Conclusion

TSDs are a strong predictor of COVID-19. The association of TSD, fever, low-grade fever or shivering, dyspnoea, arthralgia, and myalgia correctly predicts 85.7% of the results of the COVID-19 test.
2022-06-01 2022 other research-article; Journal Article abstract-available 10.3399/bjgpo.2021.0141 Study of the sensitivity and specificity of smell and taste disorders as a predictive factor of SARS-CoV-2 infection among primary care healthcare professionals: a retrospective observational study. Ruiz-Comellas A, Roura Poch P, Sauch Valmaña G, Guadalupe-Fernández V, Mendioroz Peña J, Miró Catalina Q, Vidal-Alaball J, Ramirez-Morros A. BJGP Open. 2022; 6 (2)
Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells.
Ugalde AP, Bretones G, Rodríguez D, Quesada V, [...], López-Otín C.
EMBO J. 2022; 41 (21)
DOI: 10.15252/embj.2022110727
Better understanding on interactions between SARS-CoV-2 and host cells should help to identify host factors that may be targetable to combat infection and COVID-19 pathology. To this end, we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: the lysosomal efflux transporter SPNS1 and the plasma and lysosomal membrane protein PLAC8. Functional experiments with full SARS-CoV-2 viruses confirm that loss-of-function of these genes impairs viral entry. We find that PLAC8 is a key limiting host factor, whose overexpression boosts viral infection in eight different human lung cancer cell lines. Using single-cell RNA-Seq data analyses, we demonstrate that PLAC8 is highly expressed in ciliated and secretory cells of the respiratory tract, as well as in gut enterocytes, cell types that are highly susceptible to SARS-CoV-2 infection. Proteomics and cell biology studies suggest that PLAC8 and SPNS1 regulate the autophagolysosomal compartment and affect the intracellular fate of endocytosed virions.
2022-10-04 2022 fondo-covid research-article; Journal Article abstract-available 10.15252/embj.2022110727 Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. Ugalde AP, Bretones G, Rodríguez D, Quesada V, Llorente F, Fernández-Delgado R, Jiménez-Clavero MÁ, Vázquez J, Calvo E, Tamargo-Gómez I, Mariño G, Roiz-Valle D, Maeso D, Araujo-Voces M, Español Y, Barceló C, Freije JM, López-Soto A, López-Otín C. EMBO J. 2022; 41 (21)
Chronic Rhinosinusitis and COVID-19.
Marin C, Hummel T, Liu Z, Mullol J.
J Allergy Clin Immunol Pract. 2022; 10 (6)
DOI: 10.1016/j.jaip.2022.03.003
The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.
2022-03-17 2022 other research-article; Review; Journal Article abstract-available 10.1016/j.jaip.2022.03.003 Chronic Rhinosinusitis and COVID-19. Marin C, Hummel T, Liu Z, Mullol J. J Allergy Clin Immunol Pract. 2022; 10 (6)
RNA loads of severe acute respiratory syndrome coronavirus 2 in patients with breakthrough coronavirus disease 2019 caused by the Delta and Omicron variants.
de Michelena P, Torres I, Ferrando EC, Olea B, [...], Navarro D.
Clin Microbiol Infect. 2022;
DOI: 10.1016/j.cmi.2022.09.003

Objectives

To compare the RNA loads of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal specimens collected from patients with breakthrough coronavirus disease 2019 (COVID-19) caused by the Delta variant with those in specimens collected from patients with breakthrough COVID-19 caused by the Omicron variant.

Methods

A retrospective, observational study was conducted, including 240 consecutive adult out-patients, of whom 121 (74 females; median age, 40 years) had COVID-19 due to the Omicron variant and 119 (65 females; median age, 48 years) had COVID-19 caused by the Delta variant. The viral RNA load was quantitated using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, MS, USA). The viability platinum chloride reverse transcription-PCR assay was used to discriminate between potentially infectious viral particles and free (encapsidated) viral RNA.

Results

Overall, the viral RNA loads were significantly higher (p 0.003) for the Omicron variant (median, 8.1 log10 copies/mL; range, 4.0-10.9 log10 copies/mL) than for the Delta variant (median, 7.5 log10 copies/mL; range, 3.0-11.6 log10 copies/mL). A trend towards higher viral loads was noticed for Omicron compared with that for Delta across the following time frames since vaccination: 16-90 days (median, 6.83 vs. 5.88 log10 copies/mL, respectively; range, 3.91-10.68 vs. 3.67-9.66 log10 copies/mL, respectively; p 0.10), 91-180 days (median, 8.09 vs. 7.46 log10 copies/mL, respectively; range, 4.30-10.92 vs. 3.03-11.56 log10 copies/mL, respectively; p 0.003) and 181-330 days (median, 8.56 vs. 8.10 log10 copies/mL, respectively; range, 6.51-10.29 vs. 3.03-10.61 log10 copies/mL, respectively; p 0.11). The platinum chloride treated or untreated reverse transcription-PCR cycle threshold ratio for the nucleocapsid gene as the target was slightly higher for Omicron than for Delta (median, 0.62 vs. 0.57, respectively; range, 0.57-0.98 vs. 0.61-0.87, respectively), although statistical significance was not reached (p 0.10).

Conclusion

The time elapsed since vaccination has a major impact on the RNA loads of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal specimens, particularly for the Omicron variant. The Omicron variant may be better adapted for replication in the upper respiratory tract than the Delta variant, in which this is unlikely given its more efficient generation of viral particles.
2022-09-15 2022 other brief-report; Journal Article abstract-available 10.1016/j.cmi.2022.09.003 RNA loads of severe acute respiratory syndrome coronavirus 2 in patients with breakthrough coronavirus disease 2019 caused by the Delta and Omicron variants. de Michelena P, Torres I, Ferrando EC, Olea B, González-Candelas F, Sánchez G, Navarro D. Clin Microbiol Infect. 2022;
ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.
Tamayo-Velasco Á, Peñarrubia-Ponce MJ, Álvarez FJ, de la Fuente I, [...], Andaluz-Ojeda D.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.882477
The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.
2022-04-25 2022 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2022.882477 ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points. Tamayo-Velasco Á, Peñarrubia-Ponce MJ, Álvarez FJ, de la Fuente I, Pérez-González S, Andaluz-Ojeda D. Front Med (Lausanne). 2022; 9
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)
Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa.
Zekri-Nechar K, Zamorano-León JJ, Reche C, Giner M, [...], Martínez-Martínez CH.
Dis Markers. 2022; 2022
DOI: 10.1155/2022/1118195

Background

Mitochondria have been involved in host defense upon viral infections. Factor Xa (FXa), a coagulating factor, may also have influence on mitochondrial functionalities. The aim was to analyze if in human pulmonary microvascular endothelial cells (HPMEC), the SARS-CoV-2 (COVID-19) spike protein subunits, S1 and S2 (S1+S2), could alter mitochondrial metabolism and what is the role of FXA.

Methods

HPMEC were incubated with and without recombinants S1+S2 (10 nmol/L each).

Results

In control conditions, S1+S2 failed to modify FXa expression. However, in LPS (1 μg/mL)-incubated HPMEC, S1+S2 significantly increased FXa production. LPS tended to reduce mitochondrial membrane potential with respect to control, but in higher and significant degree, it was reduced when S1+S2 were present. LPS did not significantly modify cytochrome c oxidase activity as compared with control. Addition of S1+S2 spike subunits to LPS-incubated HPMEC significantly increased cytochrome c oxidase activity with respect to control. Lactate dehydrogenase activity was also increased by S1+S2 with respect to control and LPS alone. Protein expression level of uncoupled protein-2 (UCP-2) was markedly expressed when S1+S2 were added together to LPS. Rivaroxaban (50 nmol/L), a specific FXa inhibitor, significantly reduced all the above-mentioned alterations induced by S1+S2 including UCP-2 expression.

Conclusions

In HPMEC undergoing to preinflammatory condition, COVID-19 S1+S2 spike subunits promoted alterations in mitochondria metabolism suggesting a shift from aerobic towards anaerobic metabolism that was accompanied of high FXa production. Rivaroxaban prevented all the mitochondrial metabolic changes mediated by the present COVID-19 S1 and S2 spike subunits suggesting the involvement of endogenous FXa.
2022-11-18 2022 other research-article; Journal Article abstract-available 10.1155/2022/1118195 Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa. Zekri-Nechar K, Zamorano-León JJ, Reche C, Giner M, López-de-Andrés A, Jiménez-García R, López-Farré AJ, Martínez-Martínez CH. Dis Markers. 2022; 2022
No Evidence of SARS-CoV-2 Infection in Wild Mink (Mustela lutreola and Neogale vison) from Northern Spain during the First Two Years of Pandemic.
Villanueva-Saz S, Giner J, Palomar AM, Gómez MA, [...], Fernández A.
Animals (Basel). 2022; 12 (15)
DOI: 10.3390/ani12151971
The impact of the SARS-CoV-2 pandemic on wildlife is largely unevaluated, and extended surveillance of animal species is needed to reach a consensus on the role of animals in the emergence and maintenance of SARS-CoV-2. This infection has been detected in farmed and domestic animals and wild animals, mainly in captivity. The interactions or shared resources with wildlife could represent a potential transmission pathway for the SARS-CoV-2 spill over to other wild species and could lead to health consequences or the establishment of new reservoirs in susceptible hosts. This study evaluated the presence of SARS-CoV-2 in European mink (Mustela lutreola) and American mink (Neogale vison) in Spain by enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen in serum samples and/or by RT-qPCR assays in oropharyngeal and rectal swabs. From January 2020 to February 2022, a total of 162 animals (127 European mink and 35 American mink) with no evidence of SARS-CoV-2 infection were included in the study. Antibodies against the SARS-CoV-2 were not found in the serum samples analysed (n = 126), nor was the virus amplified by RT-qPCR (n = 160 swabs). Our results suggest that the potential role of wild mink and the European mink bred in captivity and released to the wild as dispersers of SARS-CoV-2 is so far low. However, wildlife surveillance for early detection of human and animal risks should be continued. In this sense, epidemiological monitoring measures, including serology and molecular analysis, are necessary.
2022-08-03 2022 fondo-covid research-article; Journal Article abstract-available 10.3390/ani12151971 No Evidence of SARS-CoV-2 Infection in Wild Mink (<i>Mustela lutreola</i> and <i>Neogale vison</i>) from Northern Spain during the First Two Years of Pandemic. Villanueva-Saz S, Giner J, Palomar AM, Gómez MA, Põdra M, Aranda MDC, Jiménez MLÁ, Lizarraga P, Hernández R, Portillo A, Oteo JA, Ruíz-Arrondo I, Pérez MD, Tobajas AP, Verde M, Lacasta D, Marteles D, Hurtado-Guerrero R, Santiago L, Ruíz H, Fernández A. Animals (Basel). 2022; 12 (15)
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 IM; 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)
Clinical outcomes of using plasma in COVID-19 convalescent critically ill patients Resultados del uso de plasma de pacientes convalecientes de COVID-19 en pacientes críticos
Astola Hidalgo I, Fernández Rodríguez A, Martínez Revuelta E, Martínez Revuelta M, [...], Escudero Augusto D.
Med Intensiva (Engl Ed). 2022;
DOI:
2022-10-07 2022 other Case Reports; case-report Clinical outcomes of using plasma in COVID-19 convalescent critically ill patients Resultados del uso de plasma de pacientes convalecientes de COVID-19 en pacientes críticos Astola Hidalgo I, Fernández Rodríguez A, Martínez Revuelta E, Martínez Revuelta M, Ojea A, Herrero Puente P, Escudero Augusto D. Med Intensiva (Engl Ed). 2022;
Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies.
Carmona-Torre F, Mínguez-Olaondo A, López-Bravo A, Tijero B, [...], Gómez-Esteban JC.
Front Neurol. 2022; 13
DOI: 10.3389/fneur.2022.886609

Introduction

On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.

Objective

To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.

Results

Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.

Conclusion

Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.
2022-05-27 2022 other review-article; Review; Journal Article abstract-available 10.3389/fneur.2022.886609 Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies. Carmona-Torre F, Mínguez-Olaondo A, López-Bravo A, Tijero B, Grozeva V, Walcker M, Azkune-Galparsoro H, López de Munain A, Alcaide AB, Quiroga J, Del Pozo JL, Gómez-Esteban JC. Front Neurol. 2022; 13
The heart and SARS-CoV-2.
González-Calle D, Eiros R, Sánchez PL.
Med Clin (Engl Ed). 2022; 159 (9)
DOI: 10.1016/j.medcle.2022.10.001
SARS-Cov2 is currently causing a persistent Covid-19 pandemic, which poses a risk of causing long-term cardiovascular sequels in the population. The viral mechanism of cell infection through the angiotensin 2 converter enzyme receptor and the limited antiviral innate immune response are the suspected causes for a more frequent cardiovascular damage in SARS-Cov2 infection. Knowledge of: the appearance during acute infection of other cardiac conditions beyond the classical myocarditis and pericarditis), the long-term cardiac manifestations (persistent Covid-19), and the increased incidence of myocarditis and pericarditis after vaccination; it is of special interest in order to offer our patients best practices based on current scientific evidence.
2022-10-14 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.medcle.2022.10.001 The heart and SARS-CoV-2. González-Calle D, Eiros R, Sánchez PL. Med Clin (Engl Ed). 2022; 159 (9)
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)
A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors.
Jo S, Signorile L, Kim S, Kim MS, [...], Shin DH.
Int J Mol Sci. 2022; 23 (12)
DOI: 10.3390/ijms23126468
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech's Artificial Intelligence (AI) technology, SOMAIPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.
2022-06-09 2022 other research-article; Journal Article abstract-available 10.3390/ijms23126468 A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors. Jo S, Signorile L, Kim S, Kim MS, Huertas O, Insa R, Reig N, Shin DH. Int J Mol Sci. 2022; 23 (12)
Clinical progress in MSC-based therapies for the management of severe COVID-19.
Rossello-Gelabert M, Gonzalez-Pujana A, Igartua M, Santos-Vizcaino E, [...], Hernandez RM.
Cytokine Growth Factor Rev. 2022; 68
DOI: 10.1016/j.cytogfr.2022.07.002
Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.
2022-07-06 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.cytogfr.2022.07.002 Clinical progress in MSC-based therapies for the management of severe COVID-19. Rossello-Gelabert M, Gonzalez-Pujana A, Igartua M, Santos-Vizcaino E, Hernandez RM. Cytokine Growth Factor Rev. 2022; 68
Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review.
Andaluz-Ojeda D, Vidal-Cortes P, Aparisi Sanz Á, Suberviola B, [...], Cusacovich I.
World J Crit Care Med. 2022; 11 (4)
DOI: 10.5492/wjccm.v11.i4.269

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies.

Aim

To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets.

Methods

A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors.

Results

A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them.

Conclusion

Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.
2022-07-09 2022 other research-article; Journal Article abstract-available 10.5492/wjccm.v11.i4.269 Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review. Andaluz-Ojeda D, Vidal-Cortes P, Aparisi Sanz Á, Suberviola B, Del Río Carbajo L, Nogales Martín L, Prol Silva E, Nieto Del Olmo J, Barberán J, Cusacovich I. World J Crit Care Med. 2022; 11 (4)
Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants.
Ballesteros-Sanabria L, Pelaez-Prestel HF, Ras-Carmona A, Reche PA.
Biomedicines. 2022; 10 (5)
DOI: 10.3390/biomedicines10050996
The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the spike glycoprotein, which is known to bind to the receptor angiotensin converting enzyme 2 (ACE2) in host cells via the receptor-binding domain (RBD). Antibodies binding to this domain can block the interaction with the receptor and prevent viral entry into the cells. Additionally, these vaccines can also induce spike-specific T cells which could contribute to providing protection against the virus. However, the emergence of new SARS-CoV-2 variants can impair the immunity generated by COVID-19 vaccines if mutations occur in cognate epitopes, precluding immune recognition. Here, we evaluated the chance of five SARS-CoV-2 variants of concern (VOCs), Alpha, Beta, Gamma, Delta and Omicron, to escape spike-specific immunity induced by vaccines. To that end, we examined the impact of the SARS-CoV-2 variant mutations on residues located on experimentally verified spike-specific epitopes, deposited at the Immune Epitope Database, that are targeted by neutralizing antibodies or recognized by T cells. We found about 300 of such B cell epitopes, which were largely overlapping, and could be grouped into 54 B cell epitope clusters sharing ≥ 7 residues. Most of the B cell epitope clusters map in the RBD domain (39 out of 54) and 20%, 50%, 37%, 44% and 57% of the total are mutated in SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants, respectively. We also found 234 experimentally verified CD8 and CD4 T cell epitopes that were distributed evenly throughout the spike protein. Interestingly, in each SARS-CoV-2 VOC, over 87% and 79% of CD8 and CD4 T cell epitopes, respectively, are not mutated. These observations suggest that SARS-CoV-2 VOCs-particularly the Omicron variant-may be prone to escape spike-specific antibody immunity, but not cellular immunity, elicited by COVID-19 vaccines.
2022-04-26 2022 other research-article; Journal Article abstract-available 10.3390/biomedicines10050996 Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants. Ballesteros-Sanabria L, Pelaez-Prestel HF, Ras-Carmona A, Reche PA. Biomedicines. 2022; 10 (5)
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 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, Michalak I, Attia YA. Vet Q. 2021; 41 (1)
Guidelines for the prevention and management of children and adolescents with COVID-19.
Liu E, Smyth RL, Li Q, Qaseem A, [...], Li Q.
Eur J Pediatr. 2022; 181 (12)
DOI: 10.1007/s00431-022-04615-4
Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Conclusion

This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged.

What is known

• Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence.

What is new

• The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.
2022-09-16 2022 other research-article; Practice Guideline; Journal Article abstract-available 10.1007/s00431-022-04615-4 Guidelines for the prevention and management of children and adolescents with COVID-19. Liu E, Smyth RL, Li Q, Qaseem A, Florez ID, Mathew JL, Amer YS, Estill J, Lu Q, Fu Z, Lu X, Chan ES, Schwarze J, Wong GW, Fukuoka T, Ahn HS, Lee MS, Nurdiati D, Cao B, Tu W, Qian Y, Zhao S, Dong X, Luo X, Chen Z, Li G, Zhang X, Zhao X, Xu H, Xu F, Shi Y, Zhao R, Zhao Y, Lei J, Zheng X, Wang M, Yang S, Feng X, Wu L, He Z, Liu S, Wang Q, Song Y, Luo Z, Zhou Q, Guyatt G, Chen Y, Li Q. Eur J Pediatr. 2022; 181 (12)
Pulsed-Xenon Ultraviolet Light Highly Inactivates Human Coronaviruses on Solid Surfaces, Particularly SARS-CoV-2.
Bello-Perez M, Esparza I, De la Encina A, Bartolome T, [...], Usera F.
Int J Environ Res Public Health. 2022; 19 (21)
DOI: 10.3390/ijerph192113780
In the context of ongoing and future pandemics, non-pharmaceutical interventions are critical in reducing viral infections and the emergence of new antigenic variants while the population reaches immunity to limit viral transmission. This study provides information on efficient and fast methods of disinfecting surfaces contaminated with different human coronaviruses (CoVs) in healthcare settings. The ability to disinfect three different human coronaviruses (HCoV-229E, MERS-CoV, and SARS-CoV-2) on dried surfaces with light was determined for a fully characterized pulsed-xenon ultraviolet (PX-UV) source. Thereafter, the effectiveness of this treatment to inactivate SARS-CoV-2 was compared to that of conventional low-pressure mercury UVC lamps by using equivalent irradiances of UVC wavelengths. Under the experimental conditions of this research, PX-UV light completely inactivated the CoVs tested on solid surfaces since the infectivity of the three CoVs was reduced up to 4 orders of magnitude by PX-UV irradiation, with a cumulated dose of as much as 21.162 mJ/cm2 when considering all UV wavelengths (5.402 mJ/cm2 of just UVC light). Furthermore, continuous irradiation with UVC light was less efficient in inactivating SARS-CoV-2 than treatment with PX-UV light. Therefore, PX-UV light postulates as a promising decontamination measure to tackle the propagation of future outbreaks of CoVs.
2022-10-23 2022 other Journal Article abstract-available 10.3390/ijerph192113780 Pulsed-Xenon Ultraviolet Light Highly Inactivates Human Coronaviruses on Solid Surfaces, Particularly SARS-CoV-2. Bello-Perez M, Esparza I, De la Encina A, Bartolome T, Molina T, Sanjuan E, Falco A, Enjuanes L, Sola I, Usera F. Int J Environ Res Public Health. 2022; 19 (21)
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; 126 (8)
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; 126 (8)
SARS-CoV-2 RNA load in nasopharyngeal specimens from outpatients with breakthrough COVID-19 due to Omicron BA.1 and BA.2.
de Michelena P, Olea B, Torres I, González-Candelas F, [...], Navarro D.
J Med Virol. 2022; 94 (12)
DOI: 10.1002/jmv.28079
This retrospective observational study compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA load in nasopharyngeal specimens (NPs) from patients with breakthrough coronavirus disease 2019 (COVID-19) caused by the Omicron BA.1 or BA.2 sublineages. The convenience sample was composed of 277 outpatients (176 female/112 male; median age, 48 years; range, 12-97) with breakthrough COVID-19 (n = 130 due to BA.1 and n = 147 due to BA.2). All participants had completed a full vaccination schedule and 56% had received a booster vaccine dose at the time of COVID-19 breakthrough microbiological diagnosis. NPs were collected within 7 days (median 2 days) after symptom onset. The TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific) was used to estimate viral loads in NPs. Overall, viral RNA loads in NPs were comparable (p = 0.31) for BA.1 (median, 7.1 log10 copies/ml; range, 2.7-10.6) and BA.2 (median, 7.5 log10 copies/ml; range, 2.7-10.6), yet peak viral load appeared to be reached sooner for BA.2 than for BA.1 (Day 1 vs. Days 3-5; p = 0.002). Time elapsed since last vaccine dose had no significant impact on SARS-CoV-2 RNA loads in the upper respiratory tract (URT) for either BA.1 or BA.2. The data presented do not support that the transmissibility advantage of BA.2 over BA.1 is related to generation of higher viral loads in the URT early after infection.
2022-08-29 2022 other research-article; Journal Article; Observational Study abstract-available 10.1002/jmv.28079 SARS-CoV-2 RNA load in nasopharyngeal specimens from outpatients with breakthrough COVID-19 due to Omicron BA.1 and BA.2. de Michelena P, Olea B, Torres I, González-Candelas F, Navarro D. J Med Virol. 2022; 94 (12)
Emerging clinically tested detection methods for COVID-19.
Castellanos M, Somoza Á.
FEBS J. 2022;
DOI: 10.1111/febs.16469
At the time of writing, there were 486 761 597 global cases of COVID-19 with 6 142 735 confirmed deaths (World Health Organization, 4 April 2022). According to the scarcity of information about estimation of cases with mild or no symptoms, it is suggested that they could represent 25-80% of all infections. The majority of these cases remain untested, although they are infective. The molecular diagnosis of COVID-19 is based mainly on quantitative reverse transcription PCR. However, this approach faces several challenges related to the shortage of resources and people who are adequately trained to run the tests. Alternative testing methods, targeting effectively several viral compounds at different stages of the infection, have quickly emerged. However, universal systems that are specific, sensitive, affordable, easy, portable and scalable are still warranted. In this review, a comprehensive compilation of the methods available is provided.
2022-05-01 2022 fondo-covid review-article; Review; Journal Article abstract-available 10.1111/febs.16469 Emerging clinically tested detection methods for COVID-19. Castellanos M, Somoza Á. FEBS J. 2022;
Art-science multidisciplinary collaborations to address the scientific challenges posed by COVID-19.
de la Fuente J.
Ann Med. 2022; 54 (1)
DOI: 10.1080/07853890.2022.2123557
The ongoing coronavirus pandemic COVID-19 constitutes a scientific and social challenge. The application of mixed-methods research with multidisciplinary collaborations increases the success of experimental design and interpretation of results to approach scientific challenges. The objective is to develop and implement protean art algorithms with interactions between artists and scientists for scientific research in areas of molecular biology, immunology, ecology and biomedicine. In this perspective, artists were invited to contribute pieces related to the pandemic, and scientists were then challenged to contribute their view and proposed research inspired by artist contribution to face COVID-19 scientific challenges. Proposed research objectives inspired by artist contributions contribute to approach COVID-19 scientific and social challenges with results that may translate into new diagnosis and control interventions. The proposed research objectives approach vaccine protective mechanisms and the development of nutritional interventions with possible impact on boosting protective response to vaccination, the impact of fuel pollutants on host immunity and virus transmission, the possible role of ectoparasite vectors in the appearance of SARS-CoV-2 variants and virus transmission, collaboration between different sectors to contribute to virus surveillance and reduce risks of contagion, characterization of the incidence of zoonotic diseases during and after the COVID-19 pandemic in relation to modifications in the interactions between humans and reservoir animal species, evaluation of the risks associated with sexual or congenital transmission of SARS-CoV-2, development of new methods for the easy and rapid detection of very low SARS-CoV-2 virus amounts in infected but asymptomatic individuals, and understanding society perceptions about the socio-ecological relationships between decoupled environments and the risks and effects of pandemics. This approach may be used to promote social participation in science through combined scientific and artistic perspectives with impact on science and society.KEY MESSAGEMixed-methods research with multidisciplinary collaborations increases the success of experimental design and interpretation of results.Implementation of protean art algorithms through interactions between artists and scientists advances scientific research.Proposed research objectives inspired by artist contributions contribute to approach COVID-19 scientific and social challenges with results that may translate into new diagnosis and control interventions.
2022-12-01 2022 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1080/07853890.2022.2123557 Art-science multidisciplinary collaborations to address the scientific challenges posed by COVID-19. de la Fuente J. Ann Med. 2022; 54 (1)
Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages.
Jain M, Patil N, Gor D, Sharma MK, [...], Kaushik P.
Proteomes. 2022; 10 (4)
DOI: 10.3390/proteomes10040034
The novel SARS-CoV-2 variant, Omicron (B.1.1.529), is being testified, and the WHO has characterized Omicron as a variant of concern due to its higher transmissibility and very contagious behavior, immunization breakthrough cases. Here, the comparative proteomic study has been conducted on spike-protein, hACE2 of five lineages (α, β, δ, γ and Omicron. The docking was performed on spike protein- hACE-2 protein using HADDOCK, and PRODIGY was used to analyze the binding energy affinity using a reduced Haddock score. Followed by superimposition in different variant-based protein structures and calculated the esteem root mean square deviation (RMSD). This study reveals that Omicron was seen generating a monophyletic clade. Further, as α variant is the principal advanced strain after Wuhan SARS-CoV-2, and that is the reason it was showing the least likeness rate with the Omicron and connoting Omicron has developed of late with the extreme number of mutations. α variant has shown the highest binding affinity with hACE2, followed by β strain, and followed with γ. Omicron showed a penultimate binding relationship, while the δ variant was seen as having the least binding affinity. This proteomic basis in silico analysis of variable spike proteins of variants will impart light on the development of vaccines and the identification of mutations occurring in the upcoming variants.
2022-10-14 2022 other research-article; Journal Article abstract-available 10.3390/proteomes10040034 Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages. Jain M, Patil N, Gor D, Sharma MK, Goel N, Kaushik P. Proteomes. 2022; 10 (4)
Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung.
Lazar V, Raynaud J, Magidi S, Bresson C, [...], Kurzrock R.
Ther Adv Med Oncol. 2022; 14
DOI: 10.1177/17588359221133893

Background

SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC).

Methods

This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC).

Results

We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10-19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules - PD-L1, CTLA-4, PD-1, and TIGIT - are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue).

Conclusions

We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases - NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise.
2022-10-28 2022 other research-article; Journal Article abstract-available 10.1177/17588359221133893 Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high <i>ACE2</i>-expressing normal lung. Lazar V, Raynaud J, Magidi S, Bresson C, Martini JF, Galbraith S, Wunder F, Onn A, Batist G, Girard N, Lassen U, Pramesh CS, Al-Omari A, Ikeda S, Berchem G, Blay JY, Solomon B, Felip E, Tabernero J, Rubin E, Philip T, Porgador A, Berindan-Neagoe I, Schilsky RL, Kurzrock R. Ther Adv Med Oncol. 2022; 14
Experimental and natural infections of severe acute respiratory syndrome-related coronavirus 2 in pets and wild and farm animals.
Mastutik G, Rohman A, I'tishom R, Ruiz-Arrondo I, [...], de Blas I.
Vet World. 2022; 15 (3)
DOI: 10.14202/vetworld.2022.565-589
The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has spread globally and has led to extremely high mortality rates. In addition to infecting humans, this virus also has infected animals. Experimental studies and natural infections showed that dogs have a low susceptibility to SARS-CoV-2 infection, whereas domesticated cats and other animals in the family Felidae, such as lions, tigers, snow leopards, and cougars, have a high susceptibility to viral infections. In addition, wild white-tailed deer, gorillas, and otters have been found to be infected by SARS-CoV-2. Furry farm animals, such as minks, have a high susceptibility to SARS-CoV-2 infection. The virus appears to spread among minks and generate several new mutations, resulting in increased viral virulence. Furthermore, livestock animals, such as cattle, sheep, and pigs, were found to have low susceptibility to the virus, whereas chicken, ducks, turkeys, quail, and geese did not show susceptibility to SARS-CoV-2 infection. This knowledge can provide insights for the development of SARS-CoV-2 mitigation strategies in animals and humans. Therefore, this review focuses on experimental (both replication and transmission) in vitro, ex vivo, and in vivo studies of SARS-CoV-2 infections in pets and in wild and farm animals, and to provide details on the mechanism associated with natural infection.
2022-03-10 2022 other review-article; Review; Journal Article abstract-available 10.14202/vetworld.2022.565-589 Experimental and natural infections of severe acute respiratory syndrome-related coronavirus 2 in pets and wild and farm animals. Mastutik G, Rohman A, I'tishom R, Ruiz-Arrondo I, de Blas I. Vet World. 2022; 15 (3)
Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification.
Câmara GBM, Coutinho MGF, Silva LMDD, Gadelha WVDN, [...], Fernandes MAC.
Sensors (Basel). 2022; 22 (15)
DOI: 10.3390/s22155730
COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus belonging to the Coronaviridade family, a single-strand positive-sense RNA genome, has been spreading around the world and has been declared a pandemic by the World Health Organization. On 17 January 2022, there were more than 329 million cases, with more than 5.5 million deaths. Although COVID-19 has a low mortality rate, its high capacities for contamination, spread, and mutation worry the authorities, especially after the emergence of the Omicron variant, which has a high transmission capacity and can more easily contaminate even vaccinated people. Such outbreaks require elucidation of the taxonomic classification and origin of the virus (SARS-CoV-2) from the genomic sequence for strategic planning, containment, and treatment of the disease. Thus, this work proposes a high-accuracy technique to classify viruses and other organisms from a genome sequence using a deep learning convolutional neural network (CNN). Unlike the other literature, the proposed approach does not limit the length of the genome sequence. The results show that the novel proposal accurately distinguishes SARS-CoV-2 from the sequences of other viruses. The results were obtained from 1557 instances of SARS-CoV-2 from the National Center for Biotechnology Information (NCBI) and 14,684 different viruses from the Virus-Host DB. As a CNN has several changeable parameters, the tests were performed with forty-eight different architectures; the best of these had an accuracy of 91.94 ± 2.62% in classifying viruses into their realms correctly, in addition to 100% accuracy in classifying SARS-CoV-2 into its respective realm, Riboviria. For the subsequent classifications (family, genera, and subgenus), this accuracy increased, which shows that the proposed architecture may be viable in the classification of the virus that causes COVID-19.
2022-07-31 2022 other research-article; Journal Article abstract-available 10.3390/s22155730 Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification. Câmara GBM, Coutinho MGF, Silva LMDD, Gadelha WVDN, Torquato MF, Barbosa RM, Fernandes MAC. Sensors (Basel). 2022; 22 (15)
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern.
Du W, Hurdiss DL, Drabek D, Mykytyn AZ, [...], Bosch BJ.
Sci Immunol. 2022; 7 (73)
DOI: 10.1126/sciimmunol.abp9312
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.
2022-07-29 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1126/sciimmunol.abp9312 An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern. Du W, Hurdiss DL, Drabek D, Mykytyn AZ, Kaiser FK, González-Hernández M, Muñoz-Santos D, Lamers MM, van Haperen R, Li W, Drulyte I, Wang C, Sola I, Armando F, Beythien G, Ciurkiewicz M, Baumgärtner W, Guilfoyle K, Smits T, van der Lee J, van Kuppeveld FJM, van Amerongen G, Haagmans BL, Enjuanes L, Osterhaus ADME, Grosveld F, Bosch BJ. Sci Immunol. 2022; 7 (73)
An updated review of the scientific literature on the origin of SARS-CoV-2.
Domingo JL.
Environ Res. 2022; 215 (Pt 1)
DOI: 10.1016/j.envres.2022.114131
More than two and a half years have already passed since the first case of COVID-19 was officially reported (December 2019), as well as more than two years since the WHO declared the current pandemic (March 2020). During these months, the advances on the knowledge of the COVID-19 and SARS-CoV-2, the coronavirus responsible of the infection, have been very significant. However, there are still some weak points on that knowledge, being the origin of SARS-CoV-2 one of the most notorious. One year ago, I published a review focused on what we knew and what we need to know about the origin of that coronavirus, a key point for the prevention of potential future pandemics of a similar nature. The analysis of the available publications until July 2021 did not allow drawing definitive conclusions on the origin of SARS-CoV-2. Given the great importance of that issue, the present review was aimed at updating the scientific information on that origin. Unfortunately, there have not been significant advances on that topic, remaining basically the same two hypotheses on it. One of them is the zoonotic origin of SARS-CoV-2, while the second one is the possible leak of this coronavirus from a laboratory. Most recent papers do not include observational or experimental studies, being discussions and positions on these two main hypotheses. Based on the information here reviewed, there is not yet a definitive and well demonstrated conclusion on the origin of SARS-CoV-2.
2022-08-28 2022 other research-article; Review; Journal Article; Case Reports abstract-available 10.1016/j.envres.2022.114131 An updated review of the scientific literature on the origin of SARS-CoV-2. Domingo JL. Environ Res. 2022; 215 (Pt 1)
Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals.
Luczkowiak J, Labiod N, Rivas G, Rolo M, [...], Delgado R.
J Infect Dis. 2022; 225 (11)
DOI: 10.1093/infdis/jiab634
We have investigated the evolution of the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants at 8 months after Pfizer-BNT162b2 vaccination in coronavirus disease 2019 (COVID-19)-naive (n = 21) and COVID-19-convalescent (n = 21) individuals. Neutralizing levels declined for all variants (range 2- to 3.7-fold). Eight months after vaccination, a significant proportion (4/21) of naive individuals lacked detectable neutralizing activity against the highly transmissible SARS-CoV-2 delta variant. In the convalescent group, the impressive high initial humoral response resulted in detectable neutralizing antibody levels against all variants throughout this period.
2022-06-01 2022 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1093/infdis/jiab634 Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals. Luczkowiak J, Labiod N, Rivas G, Rolo M, Lasala F, Lora-Tamayo J, Mancheno-Losa M, Rial-Crestelo D, Pérez-Rivilla A, Folgueira MD, Delgado R. J Infect Dis. 2022; 225 (11)
Immunocytochemical Assessment of ACE2 and TMPRSS2 in Nasopharyngeal Swabs from SARS-CoV-2 Patients.
Peña KB, Gumà J, Guilarte C, Delamo L, [...], Parada D.
Front Biosci (Landmark Ed). 2022; 27 (7)
DOI: 10.31083/j.fbl2707217

Background

SARS-CoV-2 is a positive-sense single-stranded RNA virus. It is enveloped by four structural proteins. The entry of the virus into the host cells is mediated by spike protein binding to the angiotensin converting enzyme 2 (ACE2) and proteolytic cleavage by transmembrane protease serine 2 (TMPRSS2). In this study, we analyzed the expression of the ACE2 receptor and TMPRSS2 in cases under investigation for SARS-CoV-2 infection.

Methods

The study was carried out using the viral transport medium of consecutive nasopharyngeal swabs from 300 people under examination for SARS-CoV-2 infection. All samples underwent the SARS-CoV-2 transcriptase-mediated amplification assay (Procleix® SARS-CoV-2) to detect the virus. Immunocytochemistry was used in each sample to detect the presence of the SARS-CoV-2 nucleoprotein, the ACE2 receptor, and TMPRSS2.

Results

An immunocytochemical study with monoclonal antibody against SARS-CoV-2 viral nucleoprotein showed positivity in squamous cells. ACE2 were not detected in the squamous cells obtained from the nasopharyngeal samples.

Conclusions

SARS-CoV-2 predominantly localizes to squamous cells in cytology samples of patients with positive transcriptase-mediated amplification SARS-CoV-2 assay results. The immunocytochemical negativity for ACE2 evidenced in the present study could be related to the cellular heterogeneity present in the nasopharyngeal smear samples and could be related to variations at the genomic level. Our results suggest that SARS-CoV-2 might be present in the nasopharyngeal region because viral cell junctions are weaker. This facilitates viral concentration, infective capacity and migration to specific organs, where SARS-CoV-2 infects target cells by binding to their receptors and then entering.
2022-07-01 2022 other Journal Article abstract-available 10.31083/j.fbl2707217 Immunocytochemical Assessment of ACE2 and TMPRSS2 in Nasopharyngeal Swabs from SARS-CoV-2 Patients. Peña KB, Gumà J, Guilarte C, Delamo L, Grifol M, Pique B, Hernandez A, Casteñé H, Riu F, Parada D. Front Biosci (Landmark Ed). 2022; 27 (7)
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)
Convalescent Plasma Therapy, Therapeutic Formulations of Repurposed Drugs in 20th Century Epidemics against COVID-19: A Systematic Review.
Fernández-Lázaro D, Ortega CD, Sánchez-Serrano N, Beddar Chaib F, [...], Rodríguez-García S.
Pharmaceutics. 2022; 14 (5)
DOI: 10.3390/pharmaceutics14051020
Coronavirus 2019 disease (COVID-19) represents one of the largest pandemics the world has faced, and it is producing a global health crisis. To date, the availability of drugs to treat COVID-19 infections remains limited to supportive care although therapeutic options are being explored. Some of them are old strategies for treating infectious diseases. convalescent plasma (CP) therapy has been used successfully in other viral outbreaks in the 20th century. In this study, we systematically evaluated the effect and safety of CP therapy on hospitalized COVID-19 patients. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines using Medline (PubMed), SciELO, Cochrane Library Plus, Web of Science, and Scopus. The search included articles published up to January 2022 and was restricted to English- and Spanish-language publications. As such, investigators identified six randomized controlled trials that met the search criteria. The results determined that in hospitalized COVID-19 patients the administration of CP therapy with a volume between 200-500 mL and a single transfusion performed in 1-2 h, compared to the control group, decreased viral load, symptomatology, the period of infection, and mortality, without serious adverse effects. CP did influence clinical outcomes and may be a possible treatment option, although further studies will be necessary.
2022-05-09 2022 other review-article; Review; Journal Article abstract-available 10.3390/pharmaceutics14051020 Convalescent Plasma Therapy, Therapeutic Formulations of Repurposed Drugs in 20th Century Epidemics against COVID-19: A Systematic Review. Fernández-Lázaro D, Ortega CD, Sánchez-Serrano N, Beddar Chaib F, Jerves Donoso D, Jiménez-Callejo E, Rodríguez-García S. Pharmaceutics. 2022; 14 (5)
Non-uniform aspects of the SARS-CoV-2 intraspecies evolution reopen question of its origin.
Hassan SS, Kodakandla V, Redwan EM, Lundstrom K, [...], Uversky VN.
Int J Biol Macromol. 2022; 222 (Pt A)
DOI: 10.1016/j.ijbiomac.2022.09.184
Several hypotheses have been presented on the origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from its identification as the agent causing the current coronavirus disease 19 (COVID-19) pandemic. So far, no solid evidence has been found to support any hypothesis on the origin of this virus, and the issue continue to resurface over and over again. Here we have unfolded a pattern of distribution of several mutations in the SARS-CoV-2 proteins in 24 geo-locations across different continents. The results showed an evenly uneven distribution of the unique protein variants, distinct mutations, unique frequency of common conserved residues, and mutational residues across these 24 geo-locations. Furthermore, ample mutations were identified in the evolutionarily conserved invariant regions in the SARS-CoV-2 proteins across almost all geo-locations studied. This pattern of mutations potentially breaches the law of evolutionary conserved functional units of the beta-coronavirus genus. These mutations may lead to several novel SARS-CoV-2 variants with a high degree of transmissibility and virulence. A thorough investigation on the origin and characteristics of SARS-CoV-2 needs to be conducted in the interest of science and for the preparation of meeting the challenges of potential future pandemics.
2022-09-26 2022 other research-article; Journal Article abstract-available 10.1016/j.ijbiomac.2022.09.184 Non-uniform aspects of the SARS-CoV-2 intraspecies evolution reopen question of its origin. Hassan SS, Kodakandla V, 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 M, Sherchan SP, Lal A, Chauhan G, Baetas-da-Cruz W, Uversky VN. Int J Biol Macromol. 2022; 222 (Pt A)
Overlapping of Pulmonary Fibrosis of Postacute COVID-19 Syndrome and Tuberculosis in the Helminth Coinfection Setting in Sub-Saharan Africa.
Fonte L, Acosta A, Sarmiento ME, Norazmi MN, [...], Calderón EJ.
Trop Med Infect Dis. 2022; 7 (8)
DOI: 10.3390/tropicalmed7080157
There is an increasing attention to the emerging health problem represented by the clinical and functional long-term consequences of SARS-CoV-2 infection, referred to as postacute COVID-19 syndrome. Clinical, radiographic, and autopsy findings have shown that a high rate of fibrosis and restriction of lung function are present in patients who have recovered from COVID-19. Patients with active TB, or those who have recovered from it, have fibrotic scarred lungs and, consequently, some degree of impaired respiratory function. Helminth infections trigger predominantly type 2 immune responses and the release of regulatory and fibrogenic cytokines, such as TGF-β. Here, we analyze the possible consequences of the overlapping of pulmonary fibrosis secondary to COVID-19 and tuberculosis in the setting of sub-Saharan Africa, the region of the world with the highest prevalence of helminth infection.
2022-07-30 2022 other other; Journal Article abstract-available 10.3390/tropicalmed7080157 Overlapping of Pulmonary Fibrosis of Postacute COVID-19 Syndrome and Tuberculosis in the Helminth Coinfection Setting in Sub-Saharan Africa. Fonte L, Acosta A, Sarmiento ME, Norazmi MN, Ginori M, de Armas Y, Calderón EJ. Trop Med Infect Dis. 2022; 7 (8)
A systematic review on outbreaks of COVID-19 among children within households in the European region
Vardavas CI, Nikitara K, Aslanoglou K, Kamekis A, [...], Suk JE.
medRxiv; 2022.
DOI: 10.1101/2022.10.17.22281168

ABSTRACT

Objectives

This systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings.

Methods

This literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within household settings. The inclusion criteria were based on the PEO framework (P-Population, E-Exposure, O-Outcome) for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with pediatric index cases 1–17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either a SAR or the probability of onward infection (outcome).

Results

Of 1,819 studies originally identified, 25 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 23 studies, while there was no evidence of secondary transmission from children to other household members in two studies. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings.

Conclusions

SARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary.
2022-10-17 2022 other Preprint abstract-available 10.1101/2022.10.17.22281168 A systematic review on outbreaks of COVID-19 among children within households in the European region Vardavas CI, Nikitara K, Aslanoglou K, Kamekis A, Ramesh N, Symvoulakis E, Agaku I, Phalkey R, Leonardi-Bee J, Fernandez E, Condell O, Lamb F, Deogan C, Suk JE. medRxiv; 2022.
Should we discount the laboratory origin of COVID-19?
Segreto R, Deigin Y, McCairn K, Sousa A, [...], Zhang D.
Environ Chem Lett. 2021; 19 (4)
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; 19 (4)
Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.
Ceballos FC, Virseda-Berdices A, Resino S, Ryan P, [...], Jiménez-Sousa MÁ.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.925558

Background

metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression.

Material and methods

we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation.

Results

After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis.

Conclusions

This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.
2022-06-30 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.925558 Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation. Ceballos FC, Virseda-Berdices A, Resino S, Ryan P, Martínez-González O, Peréz-García F, Martin-Vicente M, Brochado-Kith O, Blancas R, Bartolome-Sánchez S, Vidal-Alcántara EJ, Albóniga-Díez OE, Cuadros-González J, Blanca-López N, Martínez I, Martinez-Acitores IR, Barbas C, Fernández-Rodríguez A, Jiménez-Sousa MÁ. Front Immunol. 2022; 13
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)
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 IM; 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)
A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.
Devi KP, Pourkarim MR, Thijssen M, Sureda A, [...], Khayat Kashani HR.
Pharmacol Rep. 2022; 74 (2)
DOI: 10.1007/s43440-021-00344-x
Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.
2022-01-15 2022 other brief-report; Journal Article abstract-available 10.1007/s43440-021-00344-x A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2. Devi KP, Pourkarim MR, Thijssen M, Sureda A, Khayatkashani M, Cismaru CA, Neagoe IB, Habtemariam S, Razmjouei S, Khayat Kashani HR. Pharmacol Rep. 2022; 74 (2)
A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions.
Bauer MS, Gruber S, Hausch A, Gomes PSFC, [...], Lipfert J.
Proc Natl Acad Sci U S A. 2022; 119 (14)
DOI: 10.1073/pnas.2114397119
SignificanceIn the dynamic environment of the airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability of the viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic the effect of coughing and sneezing, thereby testing the force stability of SARS-CoV-2 RBD:ACE2 interaction under physiological conditions. Our results reveal a higher force stability of SARS-CoV-2 binding to ACE2 compared to SARS-CoV-1, causing a possible fitness advantage. Our assay is sensitive to blocking agents preventing RBD:ACE2 bond formation. It will thus provide a powerful approach to investigate the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.
2022-03-21 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1073/pnas.2114397119 A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions. Bauer MS, Gruber S, Hausch A, Gomes PSFC, Milles LF, Nicolaus T, Schendel LC, Navajas PL, Procko E, Lietha D, Melo MCR, Bernardi RC, Gaub HE, Lipfert J. Proc Natl Acad Sci U S A. 2022; 119 (14)
ABO blood group is involved in the quality of the specific immune response anti-SARS-CoV-2.
Gil-Manso S, Miguens Blanco I, Motyka B, Halpin A, [...], Pion M.
Virulence. 2022; 13 (1)
DOI: 10.1080/21505594.2021.2019959
Since December 2019, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. To eradicate it, it is crucial to acquire a strong and long-lasting anti-SARS-CoV-2 immunity, by either natural infection or vaccination. We collected blood samples 12-305 days after positive polymerase chain reactions (PCRs) from 35 recovered individuals infected by SARS-CoV-2. Peripheral blood mononuclear cells were stimulated with SARS-CoV-2-derived peptide pools, such as the spike (S), nucleocapsid (N) and membrane (M) proteins, and we quantified anti-S immunoglobulins in plasma. After 10 months post-infection, we observed a sustained SARS-CoV-2-specific CD4+ T-cell response directed against M-protein, but responses against S- or N-proteins were lost over time. Besides, we demonstrated that O-group individuals presented significantly lower frequencies of specific CD4+ T-cell responses against Pep-M than non O-group individuals. The non O-group subjects also needed longer to clear the virus, and they lost cellular immune responses over time, compared to the O-group individuals, who showed a persistent specific immune response against SARS-CoV-2. Therefore, the S-specific immune response was lost over time, and individual factors might determine the sustainability of the body's defenses, which must be considered in the future design of vaccines to achieve continuous anti-SARS-CoV-2 immunity.
2022-12-01 2022 fondo-covid Journal Article abstract-available 10.1080/21505594.2021.2019959 ABO blood group is involved in the quality of the specific immune response anti-SARS-CoV-2. Gil-Manso S, Miguens Blanco I, Motyka B, Halpin A, López-Esteban R, Pérez-Fernández VA, Carbonell D, López-Fernández LA, West L, Correa-Rocha R, Pion M. Virulence. 2022; 13 (1)
Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol.
Quesada-Gomez JM, Lopez-Miranda J, Entrenas-Castillo M, Casado-Díaz A, [...], Bouillon R.
Nutrients. 2022; 14 (13)
DOI: 10.3390/nu14132716
The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin-angiotensin-bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.
2022-06-29 2022 other review-article; Review; Journal Article abstract-available 10.3390/nu14132716 Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol. Quesada-Gomez JM, Lopez-Miranda J, Entrenas-Castillo M, Casado-Díaz A, Nogues Y Solans X, Mansur JL, Bouillon R. Nutrients. 2022; 14 (13)
The Omicron (B.1.1.529) SARS-CoV-2 variant of concern also affects companion animals.
Sánchez-Morales L, Sánchez-Vizcaíno JM, Pérez-Sancho M, Domínguez L, [...], Barroso-Arévalo S.
Front Vet Sci. 2022; 9
DOI: 10.3389/fvets.2022.940710
The emergence of the Omicron variant (B.1. 1.529) has brought with it an increase in the incidence of SARS-CoV-2 disease. However, there is hardly any data on its incidence in companion animals. We have detected the presence of this new variant in domestic animals (dogs and cats) living with infected owners in Spain. None of the RT-qPCR positive animals (10.13%) presented any clinical signs and the viral loads detected were low. In addition, the shedding of viral RNA lasted a short period of time in the positive animals. Infection with this variant of concern (VOC) was confirmed by RT-qPCR and sequencing. These outcomes suggest a lower virulence of this variant in infected cats and dogs. They also demonstrate the transmission from infected humans to domestic animals and highlight the importance of active surveillance as well as genomic research to detect the presence of VOCs or mutations associated with animal hosts.
2022-08-12 2022 other research-article; Journal Article abstract-available 10.3389/fvets.2022.940710 The Omicron (B.1.1.529) SARS-CoV-2 variant of concern also affects companion animals. Sánchez-Morales L, Sánchez-Vizcaíno JM, Pérez-Sancho M, Domínguez L, Barroso-Arévalo S. Front Vet Sci. 2022; 9
Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition.
Ochando J, Camara C, Durham L, Sempere JM, [...], Lopez-Hoyos M.
Curr Res Immunol. 2022; 3
DOI: 10.1016/j.crimmu.2022.06.001
Image 1.
2022-06-18 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.crimmu.2022.06.001 Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition. Ochando J, Camara C, Durham L, Sempere JM, Lopez-Hoyos M. Curr Res Immunol. 2022; 3
Soluble angiotensin-converting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2
Troyano ND, Medina PG, Weber S, Klammer M, [...], Frias FR.
medRxiv; 2021.
DOI: 10.1101/2021.10.13.21264901

ABSTRACT

Background

There is a need for better prediction of disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble angiotensin-converting enzyme 2 (sACE2) arises from shedding of membrane ACE2 (mACE2) that is known to be a receptor for the spike protein of SARS-CoV-2; however, its value as a biomarker for disease severity is unknown. This study evaluated the predictive value of sACE2 in the context of other known biomarkers of inflammation and tissue damage (C-reactive protein [CRP], growth/differentiation factor-15 [GDF-15], interleukin-6 [IL-6], and soluble fms-like tyrosine kinase-1 [sFlt-1]) in patients with and without SARS-CoV-2 with different clinical outcomes.

Methods

For univariate analyses, median differences between biomarker levels were calculated for the following patient groups classified according to clinical outcome: reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 positive (Groups 1–4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and RT-PCR-confirmed SARS-CoV-2 negative controls (Group 7).

Results

Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in patients with SARS-CoV-2 who were admitted to hospital compared with patients who were discharged (all p<0.001), whereas levels of sACE2 were significantly lower (p<0.001). Receiver operating characteristic curve analysis of sACE2 provided cut-offs for the prediction of hospital admission of ≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%).

Conclusion

These findings support further investigation of sACE2, either as a single biomarker or as part of a panel, to predict hospitalisation risk and disease severity in patients infected with SARS-CoV-2.

HIGHLIGHTS

Noelia Diaz Troyano: Noy-Lee-ah Dee-az Tro-yah-no Better prediction of disease severity in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed. We measured soluble angiotensin-converting enzyme 2 (soluble ACE2) and other biomarkers of inflammation and tissue damage in patients recruited from Vall d’Hebron University Hospital, with and without SARS-CoV-2 and with different clinical outcomes. Levels of soluble ACE2 were significantly lower in patients with SARS-CoV-2 who had the most severe clinical outcome in all comparisons. These findings support a protective role for soluble ACE2 in SARS-CoV-2 infection and warrant further investigation of soluble ACE2 as a biomarker for disease severity in patients with SARS-CoV-2.
2021-10-14 2021 other Preprint abstract-available 10.1101/2021.10.13.21264901 Soluble angiotensin-converting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2 Troyano ND, Medina PG, Weber S, Klammer M, Barquin-DelPino R, Castillo-Ribelles L, Esteban A, Hernández-González M, Ferrer-Costa R, Pumarola T, Frias FR. medRxiv; 2021.
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)
Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia.
Cacho J, Burgos E, Molina M, Villegas A, [...], Lauzurica R.
Nefrologia (Engl Ed). 2022; 42 (3)
DOI: 10.1016/j.nefroe.2022.07.006

Background

Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases.

Methods

We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir. The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir.

Discussion

A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days.

Conclusions

Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.
2022-05-01 2022 other research-article; Journal Article; Observational Study abstract-available 10.1016/j.nefroe.2022.07.006 Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia. Cacho J, Burgos E, Molina M, Villegas A, Pérez M, Cañas L, Taco O, Juega J, Lauzurica R. Nefrologia (Engl Ed). 2022; 42 (3)
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)
COVID-19  vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations.
Jutel M, Torres MJ, Palomares O, Akdis CA, [...], Agache I.
Allergy. 2022; 77 (8)
DOI: 10.1111/all.15252
Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.
2022-03-18 2022 other research-article; Journal Article abstract-available 10.1111/all.15252 COVID-19  vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations. Jutel M, Torres MJ, Palomares O, Akdis CA, Eiwegger T, Untersmayr E, Barber D, Zemelka-Wiacek M, Kosowska A, Palmer E, Vieths S, Mahler V, Canonica WG, Nadeau K, Shamji MH, Agache I. Allergy. 2022; 77 (8)
Thrombocytopaenia and COVID-19 infection during pregnancy increases the risk of preeclampsia: a multicentre study
Defez-Martin M, Martín-Díaz M, Atienza-Ramirez S, Llorca-Colomer F, [...], Perez-Bermejo M.
Reprod Biomed Online. 2022;
DOI:
Research question: Is a low platelet count related to an increased risk of severe disease in pregnant women with active severe acute respiratory syndrome coronavirus 2 infection? Design: A cross-sectional multicentre study in pregnant women with COVID-19 confirmed by polymerase chain reaction, antigen test, antibody test, or all. Results: A total of 153 pregnant women with COVID-19 were included in the study, of whom 12.4% had thrombocytopaenia. Pregnant women with thrombocytopaenia were on average 3.1 years older (95% CI 0.18 to 6.38) than women without thrombocytopaenia. Pregnant smokers had a higher risk of thrombocytopaenia than non-smokers (OR 6.55, CI 95% 1.29 to 33.13). B Rh negative (B Rh–) pregnant women had a much higher risk of thrombocytopaenia than pregnant women with other blood groups (OR 16.83, CI 95% 1.42 to 199.8). Pregnant women with thrombocytopaenia had a much higher risk of suffering from preeclampsia (OR 16.2, CI 95% 1.35 to 193.4). Conclusions: COVID-19 infection is not a risk factor for a low platelet count in pregnant women, although the risk is increased by smoking and in women with blood group B Rh–. In case of pregnancy with thrombocytopaenia, COVID-19 infection leads to an increased risk of preeclampsia.
2022-11-06 2022 other research-article; Journal Article abstract-available Thrombocytopaenia and COVID-19 infection during pregnancy increases the risk of preeclampsia: a multicentre study Defez-Martin M, Martín-Díaz M, Atienza-Ramirez S, Llorca-Colomer F, Murillo-Llorente M, Perez-Bermejo M. Reprod Biomed Online. 2022;
Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19.
Tejerina F, Catalan P, Rodriguez-Grande C, Adan J, [...], Gregorio Marañon Microbiology ID COVID 19 Study Group.
BMC Infect Dis. 2022; 22 (1)
DOI: 10.1186/s12879-022-07153-4

Background

There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation.

Methods

We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use).

Results

We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39-67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01).

Conclusions

In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.
2022-03-03 2022 other research-article; Journal Article abstract-available 10.1186/s12879-022-07153-4 Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19. Tejerina F, Catalan P, Rodriguez-Grande C, Adan J, Rodriguez-Gonzalez C, Muñoz P, Aldamiz T, Diez C, Perez L, Fanciulli C, Garcia de Viedma D, Gregorio Marañon Microbiology ID COVID 19 Study Group. BMC Infect Dis. 2022; 22 (1)
Post COVID-19 Condition in Children and Adolescents: An Emerging Problem.
Izquierdo-Pujol J, Moron-Lopez S, Dalmau J, Gonzalez-Aumatell A, [...], Martinez-Picado J.
Front Pediatr. 2022; 10
DOI: 10.3389/fped.2022.894204
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.
2022-05-11 2022 other review-article; Review; Journal Article abstract-available 10.3389/fped.2022.894204 Post COVID-19 Condition in Children and Adolescents: An Emerging Problem. Izquierdo-Pujol J, Moron-Lopez S, Dalmau J, Gonzalez-Aumatell A, Carreras-Abad C, Mendez M, Rodrigo C, Martinez-Picado J. Front Pediatr. 2022; 10
SARS-CoV-2 Variants Identification; A Fast and Affordable Strategy Based on Partial S-Gene Targeted PCR Sequencing.
Martínez-Murcia A, Garcia-Sirera A, Navarro A, Pérez L.
Viruses. 2022; 14 (11)
DOI: 10.3390/v14112588
A considerable number of new SARS-CoV-2 lineages have emerged since the first COVID-19 cases were reported in Wuhan. As a few variants showed higher COVID-19 disease transmissibility and the ability to escape from immune responses, surveillance became relevant at that time. Single-nucleotide mutation PCR-based protocols were not always specific, and consequently, determination of a high number of informative sites was needed for accurate lineage identification. A detailed in silico analysis of SARS-CoV-2 sequences retrieved from GISAID database revealed the S gene 921 bp-fragment, positions 22784-23705 of SARS-CoV-2 reference genome, as the most informative fragment (30 variable sites) to determine relevant SARS-CoV-2 variants. Consequently, a method consisting of the PCR-amplification of this fragment, followed by Sanger's sequencing and a "single-click" informatic program based on a reference database, was developed and validated. PCR-fragments obtained from clinical SARS-CoV-2 samples were compared with homologous variant-sequences and the resulting phylogenetic tree allowed the identification of Alpha, Delta, Omicron, Beta, Gamma, and other variants. The data analysis procedure was automatized and simplified to the point that it did not require specific technical skills. The method is faster and cheaper than current whole-genome sequencing methods; it is available worldwide, and it may help to enhance efficient surveillance in the fight against the COVID-19 pandemic.
2022-11-21 2022 other research-article; Journal Article abstract-available 10.3390/v14112588 SARS-CoV-2 Variants Identification; A Fast and Affordable Strategy Based on Partial S-Gene Targeted PCR Sequencing. Martínez-Murcia A, Garcia-Sirera A, Navarro A, Pérez L. Viruses. 2022; 14 (11)
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. 2022; 59 (4)
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 Research Support, Non-U.S. Gov't; research-article; 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. 2022; 59 (4)
Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2.
Jiménez D, Martínez-Sanz J, Sainz T, Calvo C, [...], Serrano-Villar S.
J Infect. 2022; 85 (1)
DOI: 10.1016/j.jinf.2022.04.041

Background

Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease.

Methods

We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, before SARS-CoV-2 vaccine implementation, and we establish differences between infected people and participants considered resistant (highly exposed healthcare workers and children who cohabited with parents with COVID-19 without isolation and remain IgG negative).

Results

We included 74 adults, of which 47 (64%) were susceptible and 27 (36%) were resistant, and 79 children, of which 41 (52%) were susceptible and 38 (48%) were resistant. Resistant adults have significantly lower ACE2 activity in saliva than susceptible adults and non-significant higher values than susceptible and resistant children. ACE2 activity is similar in the susceptible and resistant pediatric population (p = 0.527). In contrast, we observe an increase in activity as the disease's severity increases among the adult population (mild disease vs. severe disease, 39 vs. 105 FU, p = 0.039; severe disease vs. resistant, 105 vs. 31 FU, p < 0.001).

Conclusions

using an enzymatic test, we show that ACE2 activity in saliva correlates with the susceptibility to SARS-Cov-2 infection and disease severity. Children and adults with low-susceptibility to SARS-Cov-2 infection showed the lowest ACE2 activity. These findings could inform future strategies to identify at-risk individuals.
2022-04-29 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.jinf.2022.04.041 Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2. Jiménez D, Martínez-Sanz J, Sainz T, Calvo C, Méndez-Echevarría A, Moreno E, Blázquez-Gamero D, Vizcarra P, Rodríguez M, Jenkins R, Sánchez-Conde M, Ron R, Norman F, Moreno S, Ferrer M, Serrano-Villar S. J Infect. 2022; 85 (1)
A cross-sectional serosurvey of SARS-CoV-2 and co-infections in stray cats from the second wave to the sixth wave of COVID-19 outbreaks in Spain.
Villanueva-Saz S, Martínez M, Giner J, González A, [...], Fernández A.
Vet Res Commun. 2022;
DOI: 10.1007/s11259-022-10016-7
Severe Acute Respiratory Syndrome Coronavirus 2 is the causative agent of Coronavirus Disease 2019 in humans. Among domestic animals, cats are more susceptible to SARS-CoV-2 than dogs. The detection of anti-SARS-CoV-2 antibodies in seemingly healthy cats and/or infected cats which are in close contact with infected humans has been described. The presence of animals that tested positive by serology or molecular techniques could represent a potential transmission pathway of SARS-CoV-2 that can spill over into urban wildlife. This study analyses the seroprevalence variation of SARS-CoV-2 in stray cats from different waves of outbreaks in a geographical area where previous seroepidemiological information of SARS-CoV-2 was available and investigate if SARS-CoV-2-seropositive cats were exposed to other co-infections causing an immunosuppressive status and/or a chronic disease that could lead to a SARS-CoV-2 susceptibility. For this purpose, a total of 254 stray cats from Zaragoza (Spain) were included. This analysis was carried out by the enzyme-linked immunosorbent assay using the receptor binding domain of Spike antigen and confirmed by serum virus neutralization assay. The presence of co-infections including Toxoplasma gondii, Leishmania infantum, Dirofilaria immitis, feline calicivirus, feline herpesvirus type 1, feline leukemia virus and feline immunodeficiency virus, was evaluated using different serological methods. A seropositivity of 1.57% was observed for SARS-CoV-2 including the presence of neutralizing antibodies in three cats. None of the seropositive to SARS-CoV-2 cats were positive to feline coronavirus, however, four SARS-CoV-2-seropositive cats were also seropositive to other pathogens such as L. infantum, D. immitis and FIV (n = 1), L. infantum and D. immitis (n = 1) and L. infantum alone (n = 1).Considering other pathogens, a seroprevalence of 16.54% was detected for L. infantum, 30.31% for D. immitis, 13.78%, for T. gondii, 83.86% for feline calicivirus, 42.52% for feline herpesvirus type 1, 3.15% for FeLV and 7.87% for FIV.Our findings suggest that the epidemiological role of stray cats in SARS-CoV-2 transmission is scarce, and there is no increase in seropositivity during the different waves of COVID-19 outbreaks in this group of animals. Further epidemiological surveillances are necessary to determine the risk that other animals might possess even though stray cats do not seem to play a role in transmission.
2022-10-14 2022 other research-article; Journal Article abstract-available 10.1007/s11259-022-10016-7 A cross-sectional serosurvey of SARS-CoV-2 and co-infections in stray cats from the second wave to the sixth wave of COVID-19 outbreaks in Spain. Villanueva-Saz S, Martínez M, Giner J, González A, Tobajas AP, Pérez MD, Lira-Navarrete E, González-Ramírez AM, Macías-León J, Verde M, Yzuel A, Hurtado-Guerrero R, Arias M, Santiago L, Aguiló-Gisbert J, Ruíz H, Lacasta D, Marteles D, Fernández A. Vet Res Commun. 2022;
Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b.
García-García T, Fernández-Rodríguez R, Redondo N, de Lucas-Rius A, [...], Garrido JJ.
iScience. 2022; 25 (11)
DOI: 10.1016/j.isci.2022.105444
SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is plausible to suggest that ORF7a or ORF7b could be used as biomarkers of progression in this pandemic.
2022-10-25 2022 other research-article; Journal Article abstract-available 10.1016/j.isci.2022.105444 Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b. García-García T, Fernández-Rodríguez R, Redondo N, de Lucas-Rius A, Zaldívar-López S, López-Ayllón BD, Suárez-Cárdenas JM, Jiménez-Marín Á, Montoya M, Garrido JJ. iScience. 2022; 25 (11)
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)
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 IM; 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)
Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins.
Tajuelo A, López-Siles M, Más V, Pérez-Romero P, [...], López D.
Int J Mol Sci. 2022; 23 (6)
DOI: 10.3390/ijms23062977
The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.
2022-03-10 2022 other IM; research-article; Journal Article abstract-available 10.3390/ijms23062977 Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Tajuelo A, López-Siles M, Más V, Pérez-Romero P, Aguado JM, Briz V, McConnell MJ, Martín-Galiano AJ, López D. Int J Mol Sci. 2022; 23 (6)
Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2.
Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, [...], Krishnan A.
Cell Signal. 2022; 95
DOI: 10.1016/j.cellsig.2022.110334
Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.
2022-04-21 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.cellsig.2022.110334 Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2. Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, Serrano-Aroca Á, Mishra V, Aljabali AAA, Singh SK, Chellappan DK, Gupta G, Dua K, El-Tanani M, Tambuwala MM, Krishnan A. Cell Signal. 2022; 95
CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood.
Egri N, Olivé V, Hernández-Rodríguez J, Castro P, [...], Calderón H.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.848586
Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.
2022-07-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.848586 CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood. Egri N, Olivé V, Hernández-Rodríguez J, Castro P, De Guzman C, Heredia L, Segura AC, Fernandez MD, de Moner N, Torradeflot M, Ballús J, Martinez R, Vazquez M, Costa MV, Dobaño C, Mazza M, Mazzotti L, Pascal M, Juan M, González-Navarro EA, Calderón H. Front Immunol. 2022; 13
COVID-19 in Pregnant Women, Maternal-Fetal Involvement, and Vertical Mother-to-Child Transmission: A Systematic Review.
Sánchez-García JC, Carrascosa Moreno NP, Tovar-Gálvez MI, Cortés-Martín J, [...], Rodríguez-Blanque R.
Biomedicines. 2022; 10 (10)
DOI: 10.3390/biomedicines10102554
Pregnant women are included in the COVID-19 risk groups even if they do not have any pathology. This requires an analysis of research focused on pregnant women to understand the impact of SARS-CoV-2 on their condition. There is also a need to know whether there is vertical mother-to-child transmission, as well as other consequences in case the pregnant woman is infected and COVID-19 positive. A systematic review was carried out to analyze the existing information on the complications of a pregnant woman infected with the SARS-CoV-2 coronavirus and the possibility of vertical transmission from mother to child, registered in the PROSPERO website and searched in the PubMed, Scopus, CINAHL, and Cochrane Library databases. Finally, 22 articles were included in the review. The review suggests that vertical transmission from mother to child could be exceptionally possible at the time of delivery or breastfeeding, but not through the placenta. It is interesting to point out the good acceptance of vaccination by pregnant women, which may be the reason for the low infectivity. Further research on pregnant women should be carried out to provide evidence on vertical mother-to-child transmission and the role of breast milk in relation to SARS-CoV-2.
2022-10-13 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10102554 COVID-19 in Pregnant Women, Maternal-Fetal Involvement, and Vertical Mother-to-Child Transmission: A Systematic Review. Sánchez-García JC, Carrascosa Moreno NP, Tovar-Gálvez MI, Cortés-Martín J, Liñán-González A, Alvarado Olmedo L, Rodríguez-Blanque R. Biomedicines. 2022; 10 (10)
Flexible multiplex PCR to detect SARS-CoV-2, coronavirus OC43 and influenza A virus in nasopharyngeal swab samples.
Pelegri-Martinez E, Guruceaga X, Martin-Souto L, Abad-Diaz-de-Cerio A, [...], Ramirez-Garcia A.
J Appl Microbiol. 2022; 133 (6)
DOI: 10.1111/jam.15788

Introduction

Quantitative reverse transcription PCR (RT-qPCR) is the leading tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given that it will almost certainly continue to coexist with other respiratory viruses in the coming years, our study aimed to design a multiplex PCR system not affected by supplier outages and with reduced cost compared to the existing commercially available kits.

Methods and results

In this study, combinations of four primers/probe sets were used to construct a flexible RT-qPCR assay which is capable of discriminating between SARS-CoV-2 and the seasonal human coronavirus HCoV-OC43, or even influenza A virus. Additionally, the human RPP30 gene was used as an internal control. To demonstrate the robustness of the assay, it was applied to a collection of 150 clinical samples. The results showed 100% sensitivity and specificity compared to the automatized system used at the hospital and were better when indeterminate samples were analysed.

Conclusions

This study provides an efficient method for the simultaneous detection of SARS-CoV-2, HCoV-OC43 and influenza A virus, and its efficacy has been tested on clinical samples showing outstanding results.

Significance and impact of the study

The multiplex RT-qPCR design offers an accessible and economical alternative to commercial detection kits for hospitals and laboratories with limited economic resources or facing situations of supply shortage.
2022-09-07 2022 other research-article; Journal Article abstract-available 10.1111/jam.15788 Flexible multiplex PCR to detect SARS-CoV-2, coronavirus OC43 and influenza A virus in nasopharyngeal swab samples. Pelegri-Martinez E, Guruceaga X, Martin-Souto L, Abad-Diaz-de-Cerio A, Rementeria A, Dominguez-Monedero A, Gallego M, Martinez O, Arana-Arri E, Aranzamendi M, Ramirez-Garcia A. J Appl Microbiol. 2022; 133 (6)
Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cTFH cells.
García-Jiménez ÁF, Cáceres-Martell Y, Fernández-Soto D, Martínez Fleta P, [...], Reyburn HT.
J Leukoc Biol. 2022; 112 (2)
DOI: 10.1002/jlb.4covcra0721-356rrr
Multiple questions about SARS-CoV-2 humoral and cellular immunity remain unanswered. One key question is whether preexisting memory T or B cells, specific for related coronaviruses in SARS-CoV-2-unexposed individuals, can recognize and suppress COVID-19, but this issue remains unclear. Here, we demonstrate that antibody responses to SARS-CoV-2 antigens are restricted to serum samples from COVID-19 convalescent individuals. In contrast, cross-reactive T cell proliferation and IFN-γ production responses were detected in PBMCs of around 30% of donor samples collected prepandemic, although we found that these prepandemic T cell responses only elicited weak cTFH activation upon stimulation with either HCoV-OC43 or SARS-CoV-2 NP protein. Overall, these observations confirm that T cell cross-reactive with SARS-CoV-2 antigens are present in unexposed people, but suggest that the T cell response to HCoV-OC43 could be deficient in some important aspects, like TFH expansion, that might compromise the generation of cross-reactive TFH cells and antibodies. Understanding these differences in cellular responses may be of critical importance to advance in our knowledge of immunity against SARS-CoV-2.
2022-04-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1002/jlb.4covcra0721-356rrr Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cT<sub>FH</sub> cells. García-Jiménez ÁF, Cáceres-Martell Y, Fernández-Soto D, Martínez Fleta P, Casasnovas JM, Sánchez-Madrid F, Frade JMR, Valés-Gómez M, Reyburn HT. J Leukoc Biol. 2022; 112 (2)
Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2.
Díaz-Troyano N, Gabriel-Medina P, Weber S, Klammer M, [...], Rodríguez-Frías F.
Diagnostics (Basel). 2022; 12 (4)
DOI: 10.3390/diagnostics12040886
Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): RT-PCR-confirmed SARS-CoV-2 positive (Groups 1-4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and 'SARS-CoV-2 unexposed' patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.
2022-04-01 2022 other research-article; Journal Article abstract-available 10.3390/diagnostics12040886 Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2. Díaz-Troyano N, Gabriel-Medina P, Weber S, Klammer M, Barquín-DelPino R, Castillo-Ribelles L, Esteban A, Hernández-González M, Ferrer-Costa R, Pumarola T, Rodríguez-Frías F. Diagnostics (Basel). 2022; 12 (4)
Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease.
Theodorakopoulou MP, Alexandrou ME, Boutou AK, Ferro CJ, [...], Sarafidis P.
Clin Kidney J. 2022; 15 (3)
DOI: 10.1093/ckj/sfab272
Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin-angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.
2021-12-14 2021 other review-article; Review; Journal Article abstract-available 10.1093/ckj/sfab272 Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease. Theodorakopoulou MP, Alexandrou ME, Boutou AK, Ferro CJ, Ortiz A, Sarafidis P. Clin Kidney J. 2022; 15 (3)
Potent Virucidal Activity In Vitro of Photodynamic Therapy with Hypericum Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E.
Praena B, Mascaraque M, Andreu S, Bello-Morales R, [...], Juarranz Á.
Pharmaceutics. 2022; 14 (11)
DOI: 10.3390/pharmaceutics14112364
The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new virucidal treatments. In this sense, the use of photodynamic therapy (PDT) with white light, to take advantage of the sunlight, is a potent strategy for decreasing the virulence and pathogenicity of the virus. Here, we report the virucidal effect of PDT based on Hypericum extract (HE) in combination with white light, which exhibits an inhibitory activity of the human coronavirus HCoV-229E on hepatocarcinoma Huh-7 cells. Moreover, despite continuous exposure to white light, HE has long durability, being able to maintain the prevention of viral infection. Given its potent in vitro virucidal capacity, we propose HE in combination with white light as a promising candidate to fight against SARS-CoV-2 as a virucidal compound.
2022-11-02 2022 other research-article; Journal Article abstract-available 10.3390/pharmaceutics14112364 Potent Virucidal Activity In Vitro of Photodynamic Therapy with <i>Hypericum</i> Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E. Praena B, Mascaraque M, Andreu S, Bello-Morales R, Abarca-Lachen E, Rapozzi V, Gilaberte Y, González S, López-Guerrero JA, Juarranz Á. Pharmaceutics. 2022; 14 (11)
Thrombosis, cancer, and COVID-19.
Brito-Dellan N, Tsoukalas N, Font C.
Support Care Cancer. 2022; 30 (10)
DOI: 10.1007/s00520-022-07098-z
Cancer and coronavirus disease 2019 (COVID-19) have unusual similarities: they both result in a markedly elevated risk of thrombosis, exceptionally high D-dimer levels, and the failure of anticoagulation therapy in some cases. Cancer patients are more vulnerable to COVID-19 infection and have a higher mortality rate. Science has uncovered much about SARS-CoV-2, and made extraordinary and unprecedented progress on the development of various treatment strategies and COVID-19 vaccines. In this review, we discuss known data on cancer-associated thrombosis (CAT), SARS-CoV-2 infection, and COVID-19 vaccines and discuss considerations for managing CAT in patients with COVID-19. Cancer patients should be given priority for COVID-19 vaccination; however, they may demonstrate a weaker immune response to COVID-19 vaccines than the general population. Currently, the Centers for Disease Control and Prevention recommends an additional dose and booster shot of the COVID-19 vaccine after the primary series in patients undergoing active cancer treatment for solid tumors or hematological cancers, recipients of stem cell transplant within the last 2 years, those taking immunosuppressive medications, and those undergoing active treatment with high-dose corticosteroids or other drugs that suppress the immune response. The mainstay of thrombosis treatment in patients with cancer and COVID-19 is anticoagulation therapy.
2022-05-14 2022 other research-article; Review; Journal Article abstract-available 10.1007/s00520-022-07098-z Thrombosis, cancer, and COVID-19. Brito-Dellan N, Tsoukalas N, Font C. Support Care Cancer. 2022; 30 (10)
The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.
Beltrán-Camacho L, Eslava-Alcón S, Rojas-Torres M, Sánchez-Morillo D, [...], Durán-Ruiz MC.
Mol Med. 2022; 28 (1)
DOI: 10.1186/s10020-022-00465-w

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential.

Methods

We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs.

Results

Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus.

Conclusions

The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection.
2022-04-09 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s10020-022-00465-w The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo. Beltrán-Camacho L, Eslava-Alcón S, Rojas-Torres M, Sánchez-Morillo D, Martinez-Nicolás MP, Martín-Bermejo V, de la Torre IG, Berrocoso E, Moreno JA, Moreno-Luna R, Durán-Ruiz MC. Mol Med. 2022; 28 (1)
Divergent SARS-CoV-2-specific T cell responses in intensive care unit workers following mRNA COVID-19 vaccination.
Salgado Del Riego E, Saiz ML, Corte-Iglesias V, Leoz Gordillo B, [...], Suarez-Alvarez B.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.942192
The cellular immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to full mRNA COVID-19 vaccination could be variable among healthy individuals. Studies based only in specific antibody levels could show an erroneous immune protection at long times. For that, we analyze the antibody levels specific to the S protein and the presence of SARS-CoV-2-specific T cells by ELISpot and AIM assays in intensive care unit (ICU) workers with no antecedents of COVID-19 and vaccinated with two doses of mRNA COVID-19 vaccines. All individuals were seronegative for the SARS-CoV-2 protein S before vaccination (Pre-v), but 34.1% (14/41) of them showed pre-existing T lymphocytes specific for some viral proteins (S, M and N). One month after receiving two doses of COVID-19 mRNA vaccine (Post-v1), all cases showed seroconversion with high levels of total and neutralizing antibodies to the spike protein, but six of them (14.6%) had no T cells reactive to the S protein. Specifically, they lack of specific CD8+ T cells, but maintain the contribution of CD4+ T cells. Analysis of the immune response against SARS-CoV-2 at 10 months after full vaccination (Post-v10), exhibited a significant reduction in the antibody levels (p<0.0001) and protein S-reactive T cells (p=0.0073) in all analyzed individuals, although none of the individuals become seronegative and 77% of them maintained a competent immune response. Thus, we can suggest that the immune response to SARS-CoV-2 elicited by the mRNA vaccines was highly variable among ICU workers. A non-negligible proportion of individuals did not develop a specific T cell response mediated by CD8+ T cells after vaccination, that may condition the susceptibility to further viral infections with SARS-CoV-2. By contrast, around 77% of individuals developed strong humoral and cellular immune responses to SARS-CoV-2 that persisted even after 10 months. Analysis of the cellular immune response is highly recommended for providing exact information about immune protection against SARS-CoV-2.
2022-10-06 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.942192 Divergent SARS-CoV-2-specific T cell responses in intensive care unit workers following mRNA COVID-19 vaccination. Salgado Del Riego E, Saiz ML, Corte-Iglesias V, Leoz Gordillo B, Martin-Martin C, Rodríguez-Pérez M, Escudero D, Lopez-Larrea C, Suarez-Alvarez B. Front Immunol. 2022; 13
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. 2022; 225 (6)
DOI: 10.1093/infdis/jiab604
Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and 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 nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.
2022-03-01 2022 fondo-covid brief-report; Research Support, Non-U.S. Gov't; 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. 2022; 225 (6)
SARS-CoV-2 accessory protein 7b forms homotetramers in detergent.
Surya W, Queralt-Martin M, Mu Y, Aguilella VM, [...], Torres J.
Virol J. 2022; 19 (1)
DOI: 10.1186/s12985-022-01920-0
A global pandemic is underway caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome, like its predecessor SARS-CoV, contains open reading frames that encode accessory proteins involved in virus-host interactions active during infection and which likely contribute to pathogenesis. One of these accessory proteins is 7b, with only 44 (SARS-CoV) and 43 (SARS-CoV-2) residues. It has one predicted transmembrane domain fully conserved, which suggests a functional role, whereas most variability is contained in the predicted cytoplasmic C-terminus. In SARS-CoV, 7b protein is expressed in infected cells, and the transmembrane domain was necessary and sufficient for Golgi localization. Also, anti-p7b antibodies have been found in the sera of SARS-CoV convalescent patients. In the present study, we have investigated the hypothesis that SARS-2 7b protein forms oligomers with ion channel activity. We show that in both SARS viruses 7b is almost completely α-helical and has a single transmembrane domain. In SDS, 7b forms various oligomers, from monomers to tetramers, but only monomers when exposed to reductants. Combination of SDS gel electrophoresis and analytical ultracentrifugation (AUC) in both equilibrium and velocity modes suggests a dimer-tetramer equilibrium, but a monomer-dimer-tetramer equilibrium in the presence of reductant. This data suggests that although disulfide-linked dimers may be present, they are not essential to form tetramers. Inclusion of pentamers or higher oligomers in the SARS-2 7b model were detrimental to fit quality. Preliminary models of this association was generated with AlphaFold2, and two alternative models were exposed to a molecular dynamics simulation in presence of a model lipid membrane. However, neither of the two models provided any evident pathway for ions. To confirm this, SARS-2 p7b was studied using Planar Bilayer Electrophysiology. Addition of p7b to model membranes produced occasional membrane permeabilization, but this was not consistent with bona fide ion channels made of a tetrameric assembly of α-helices.
2022-11-21 2022 other Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1186/s12985-022-01920-0 SARS-CoV-2 accessory protein 7b forms homotetramers in detergent. Surya W, Queralt-Martin M, Mu Y, Aguilella VM, Torres J. Virol J. 2022; 19 (1)
Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.
Cuadrado A, Del Barrio M, Fortea JI, Amigo L, [...], Fábrega E.
Hepatol Commun. 2022; 6 (7)
DOI: 10.1002/hep4.1937
Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 μg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.
2022-03-28 2022 other research-article; Journal Article abstract-available 10.1002/hep4.1937 Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients. Cuadrado A, Del Barrio M, Fortea JI, Amigo L, San Segundo D, Rodriguez-Cundin MP, Rebollo MH, Fernandez-Santiago R, Castillo F, Achalandabaso M, Echeverri J, Anderson EJ, Rodríguez-Sanjuan JC, López-Hoyos M, Crespo J, Fábrega E. Hepatol Commun. 2022; 6 (7)
Is There Less Alteration of Smell Sensation in Patients With Omicron SARS-CoV-2 Variant Infection?
Rodriguez-Sevilla JJ, Güerri-Fernádez R, Bertran Recasens B.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.852998
The ongoing pandemic Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern in terms of public health Within the symptoms secondary to SARS-CoV-2 infection, hyposmia and anosmia have emerged as characteristic symptoms during the onset of the pandemic. Although many researchers have investigated the etiopathogenesis of this phenomenon, the main cause is not clear. The appearance of the new variant of concern Omicron has meant a breakthrough in the chronology of this pandemic, presenting greater transmissibility and less severity, according to the first reports. We have been impressed by the decrease in anosmia reported with this new variant and in patients reinfected or who had received vaccination before becoming infected. Based on the literature published to date, this review proposes different hypotheses to explain this possible lesser affectation of smell. On the one hand, modifications in the SARS-CoV-2 spike protein could produce changes in cell tropism and interaction with proteins that promote virus uptake (ACE-2, TMPRSS2, and TMEM16F). These proteins can be found in the sustentacular cells and glandular cells of the olfactory epithelium. Second, due to the characteristics of the virus or previous immunity (infection or vaccination), there could be less systemic or local inflammation that would generate less cell damage in the olfactory epithelium and/or in the central nervous system.
2022-04-12 2022 other research-article; Journal Article abstract-available 10.3389/fmed.2022.852998 Is There Less Alteration of Smell Sensation in Patients With Omicron SARS-CoV-2 Variant Infection? Rodriguez-Sevilla JJ, Güerri-Fernádez R, Bertran Recasens B. Front Med (Lausanne). 2022; 9
Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION.
Kloka J, Friedrichson B, Dauth S, Foldenauer AC, [...], IXION Collaboration Group.
Trials. 2022; 23 (1)
DOI: 10.1186/s13063-022-06609-x

Background

More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients.

Methods

IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability.

Discussion

With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for.

Trial registration

EudraCT 2021-005059-35 . Registered on 12 December 2021. Study Code TMP-2204-2021-47.
2022-08-19 2022 other Clinical Trial, Phase II; research-article; Randomized Controlled Trial; Journal Article abstract-available 10.1186/s13063-022-06609-x Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION. Kloka J, Friedrichson B, Dauth S, Foldenauer AC, Bulczak-Schadendorf A, Vehreschild MJGT, Matos FM, Riera-Mestre A, van Asselt ADI, De Robertis E, Juskeviciene VT, Meybohm P, Tomescu D, Lacombe K, Stehouwer CDA, Zacharowski K, IXION Collaboration Group. Trials. 2022; 23 (1)
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. 2022; 84 (3)
DOI: 10.1016/j.jinf.2021.11.002
2021-11-06 2021 other Letter; Comment; Research Support, Non-U.S. Gov't 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. 2022; 84 (3)
Self-Assembling Protein Nanoparticles in the Design of Vaccines: 2022 Update.
Morales-Hernández S, Ugidos-Damboriena N, López-Sagaseta J.
Vaccines (Basel). 2022; 10 (9)
DOI: 10.3390/vaccines10091447
Vaccines constitute a pillar in the prevention of infectious diseases. The unprecedented emergence of novel immunization strategies due to the COVID-19 pandemic has again positioned vaccination as a pivotal measure to protect humankind and reduce the clinical impact and socioeconomic burden worldwide. Vaccination pursues the ultimate goal of eliciting a protective response in immunized individuals. To achieve this, immunogens must be efficiently delivered to prime the immune system and produce robust protection. Given their safety, immunogenicity, and flexibility to display varied and native epitopes, self-assembling protein nanoparticles represent one of the most promising immunogen delivery platforms. Currently marketed vaccines against the human papillomavirus, for instance, illustrate the potential of these nanoassemblies. This review is intended to provide novelties, since 2015, on the ground of vaccine design and self-assembling protein nanoparticles, as well as a comparison with the current emergence of mRNA-based vaccines.
2022-09-02 2022 other review-article; Review; Journal Article abstract-available 10.3390/vaccines10091447 Self-Assembling Protein Nanoparticles in the Design of Vaccines: 2022 Update. Morales-Hernández S, Ugidos-Damboriena N, López-Sagaseta J. Vaccines (Basel). 2022; 10 (9)
Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.
Muskiet FAJ, Carrera-Bastos P, Pruimboom L, Lucia A, [...], Furman D.
Nutrients. 2022; 14 (7)
DOI: 10.3390/nu14071388
Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.
2022-03-26 2022 other review-article; Review; Journal Article abstract-available 10.3390/nu14071388 Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19. Muskiet FAJ, Carrera-Bastos P, Pruimboom L, Lucia A, Furman D. Nutrients. 2022; 14 (7)
Assessing wastewater-based epidemiology for the prediction of SARS-CoV-2 incidence in Catalonia.
Joseph-Duran B, Serra-Compte A, Sàrrias M, Gonzalez S, [...], Arnaldos M.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-18518-9
While wastewater-based epidemiology has proven a useful tool for epidemiological surveillance during the COVID-19 pandemic, few quantitative models comparing virus concentrations in wastewater samples and cumulative incidence have been established. In this work, a simple mathematical model relating virus concentration and cumulative incidence for full contagion waves was developed. The model was then used for short-term forecasting and compared to a local linear model. Both scenarios were tested using a dataset composed of samples from 32 wastewater treatment plants and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence data covering the corresponding geographical areas during a 7-month period, including two contagion waves. A population-averaged dataset was also developed to model and predict the incidence over the full geography. Overall, the mathematical model based on wastewater data showed a good correlation with cumulative cases and allowed us to anticipate SARS-CoV-2 incidence in one week, which is of special relevance in situations where the epidemiological monitoring system cannot be fully implemented.
2022-09-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-022-18518-9 Assessing wastewater-based epidemiology for the prediction of SARS-CoV-2 incidence in Catalonia. Joseph-Duran B, Serra-Compte A, Sàrrias M, Gonzalez S, López D, Prats C, Català M, Alvarez-Lacalle E, Alonso S, Arnaldos M. Sci Rep. 2022; 12 (1)
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
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)
Inflammation and oxidative stress, the links between obesity and COVID-19: a narrative review.
Moreno-Fernandez J, Ochoa J, Ojeda ML, Nogales F, [...], Díaz-Castro J.
J Physiol Biochem. 2022; 78 (3)
DOI: 10.1007/s13105-022-00887-4
COVID-19, an acute respiratory disease caused by SARS-CoV-2, has rapidly become a pandemic. On the other hand, obesity is also reaching dramatic dimensions and it is a risk factor for morbidity and premature mortality. Obesity has been linked to a high risk of serious-associated complications to COVID-19, due to the increased risk of concomitant chronic diseases, which highlights the health public relevance of the topic. Obese subjects have a pro-inflammatory environment, which can further exacerbate COVID-19-induced inflammation and oxidative stress, explaining the increased risk of serious complications in these patients. Another factor that favors infection in obese patients is the high expression of ACE2 receptors in the adipose tissue. The negative impact of COVID-19 in obesity is also associated with a decrease in respiratory function, the concurrence of multiple comorbidities, a low-degree chronic inflammatory state, immunocompromised situation, and therefore a higher rate of hospitalization, mechanical ventilation, in-hospital complications such as pneumonia, and death. In this review, the link between obesity and COVID-19 was analyzed, exploring the potential common mechanisms in both diseases, with special attention to oxidative stress and inflammation, due to the crucial role of both pathways in the development of the disease.
2022-03-22 2022 other review-article; Review; Journal Article abstract-available 10.1007/s13105-022-00887-4 Inflammation and oxidative stress, the links between obesity and COVID-19: a narrative review. Moreno-Fernandez J, Ochoa J, Ojeda ML, Nogales F, Carreras O, Díaz-Castro J. J Physiol Biochem. 2022; 78 (3)
The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids.
Gonzalez-Barcala FJ, Nieto-Fontarigo JJ, Mendez-Brea P, Salgado FJ.
ERJ Open Res. 2022; 8 (2)
DOI: 10.1183/23120541.00179-2022
The impact of ICS on the prognosis for #COVID19 in #asthma patients requires a thorough evaluation of a range of factors that interact in this process, in order to draw solid conclusions, since at the present time the debate continues https://bit.ly/3xLNBrc.
2022-04-01 2022 other Editorial abstract-available 10.1183/23120541.00179-2022 The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids. Gonzalez-Barcala FJ, Nieto-Fontarigo JJ, Mendez-Brea P, Salgado FJ. ERJ Open Res. 2022; 8 (2)
A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens
Schlegel J, Porebski B, Andronico L, Hanke L, [...], Sezgin E.
bioRxiv; 2022.
DOI: 10.1101/2022.10.10.511545
Speed is key during infectious disease outbreaks. It is essential, for example, to identify critical host binding factors to the pathogens as fast as possible. The complexity of host plasma membrane is often a limiting factor hindering fast and accurate determination of host binding factors as well as high-throughput screening for neutralizing antimicrobial drug targets. Here we describe a multi-parametric and high-throughput platform tackling this bottleneck and enabling fast screens for host binding factors as well as new antiviral drug targets. The sensitivity and robustness of our platform was validated by blocking SARS-CoV-2 spike particles with nanobodies and IgGs from human serum samples.

Teaser

A fast screening platform tackling host-pathogen interactions.
2022-10-11 2022 other Preprint abstract-available 10.1101/2022.10.10.511545 A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens Schlegel J, Porebski B, Andronico L, Hanke L, Edwards S, Brismar H, Murrell B, McInerney G, Fernandez-Capetillo O, Sezgin E. bioRxiv; 2022.
Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions.
Lachén-Montes M, Mendizuri N, Ausín K, Echaide M, [...], Santamaría E.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.866564
One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
2022-09-08 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.866564 Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions. Lachén-Montes M, Mendizuri N, Ausín K, Echaide M, Blanco E, Chocarro L, de Toro M, Escors D, Fernández-Irigoyen J, Kochan G, Santamaría E. Front Immunol. 2022; 13
Acute necro-hemorrhagic pancreatitis during SARS-CoV-2 infection.
Arche Banzo MJ, Matute Guerrero A, Herrero García S.
Med Clin (Engl Ed). 2022; 158 (7)
DOI: 10.1016/j.medcle.2021.06.015
2022-02-21 2022 other letter; Journal Article 10.1016/j.medcle.2021.06.015 Acute necro-hemorrhagic pancreatitis during SARS-CoV-2 infection. Arche Banzo MJ, Matute Guerrero A, Herrero García S. Med Clin (Engl Ed). 2022; 158 (7)
Detection of SARS-CoV-2 in a dog with hemorrhagic diarrhea.
Padilla-Blanco M, Vega S, Enjuanes L, Morey A, [...], Rubio-Guerri C.
BMC Vet Res. 2022; 18 (1)
DOI: 10.1186/s12917-022-03453-8

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected several animal species, including dogs, presumably via human-to-animal transmission. Most infected dogs reported were asymptomatic, with low viral loads. However, in this case we detected SARS-CoV-2 in a dog from the North African coastal Spanish city of Ceuta presenting hemorrhagic diarrhea, a disease also reported earlier on in an infected dog from the USA.

Case presentation

In early January 2021, a West Highland Terrier pet dog from Ceuta (Spain) presented hemorrhagic diarrhea with negative tests for candidate microbial pathogens. Since the animal was in a household whose members suffered SARS-CoV-2 in December 2020, dog feces were analyzed for SARS-CoV-2, proving positive in a two-tube RT-PCR test, with confirmation by sequencing a 399-nucleotide region of the spike (S) gene. Furthermore, next-generation sequencing (NGS) covered > 90% SARS-CoV-2 genome sequence, allowing to classify it as variant B.1.177. Remarkably, the sequence revealed the Ile402Val substitution in the spike protein (S), of potential concern because it mapped in the receptor binding domain (RBD) that mediates virus interaction with the cell. NGS reads mapping to bacterial genomes showed that the dog fecal microbiome fitted best the characteristic microbiome of dog's acute hemorrhagic diarrhea.

Conclusion

Our findings exemplify dog infection stemming from the human SARS-CoV-2 pandemic, providing nearly complete-genome sequencing of the virus, which is recognized as belonging to the B.1.177 variant, adding knowledge on variant circulation in a geographic region and period for which there was little viral variant characterization. A single amino acid substitution found in the S protein that could have been of concern is excluded to belong to this category given its rarity and intrinsic nature. The dog's pathology suggests that SARS-CoV-2 could affect the gastrointestinal tract of the dog.
2022-10-12 2022 other Journal Article; Case Reports abstract-available 10.1186/s12917-022-03453-8 Detection of SARS-CoV-2 in a dog with hemorrhagic diarrhea. Padilla-Blanco M, Vega S, Enjuanes L, Morey A, Lorenzo T, Marín C, Ivorra C, Maiques E, Rubio V, Rubio-Guerri C. BMC Vet Res. 2022; 18 (1)
The Effects of Vitamin D Supplementation in COVID-19 Patients: A Systematic Review.
Feiner Solís Á, Avedillo Salas A, Luesma Bartolomé MJ, Santander Ballestín S.
Int J Mol Sci. 2022; 23 (20)
DOI: 10.3390/ijms232012424
Vitamin D has an immune-modulating effect on respiratory tract infections. For this reason, it has been proposed as part of the treatment in COVID-19. Furthermore, vitamin D deficiency has been associated with worse clinical outcomes of this disease. The aim of this systematic review was to determine whether vitamin D supplementation modifies the disease course. Therefore, eleven studies involving randomised clinical trials are analysed, in which groups of COVID-19 patients with or without vitamin D supplementation as part of the treatment are compared. A control group was treated with best available therapy, and in some of the clinical trials, also with a placebo. According to the outcomes, it seems that patients benefit from receiving a daily or maintained in time vitamin D dose regardless of vitamin D serum levels at the beginning of the trial. The administration of a single vitamin D dose does not seem to have any effect on the health status of these patients. However, the outcomes are heterogeneous and larger clinical trials are necessary.
2022-10-17 2022 other Systematic Review; review-article; Review; Journal Article abstract-available 10.3390/ijms232012424 The Effects of Vitamin D Supplementation in COVID-19 Patients: A Systematic Review. Feiner Solís Á, Avedillo Salas A, Luesma Bartolomé MJ, Santander Ballestín S. Int J Mol Sci. 2022; 23 (20)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and humoral responses against different variants of concern in domestic pet animals and stray cats from North-Eastern Spain.
Fernández-Bastit L, Marfil S, Pradenas E, Valle R, [...], Segalés J.
Transbound Emerg Dis. 2022;
DOI: 10.1111/tbed.14714
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic in humans, is able to infect several domestic, captive and wildlife animal species. Since reverse zoonotic transmission to pets has been demonstrated, it is crucial to determine their role in the epidemiology of the disease to prevent further spillover events and major spread of SARS-CoV-2. In the present study, we determined the presence of virus and the seroprevalence to SARS-CoV-2, as well as the levels of neutralizing antibodies (nAbs) against several variants of concern (VOCs) in pets (cats, dogs and ferrets) and stray cats from North-Eastern of Spain. We confirmed that cats and dogs can be infected by different VOCs of SARS-CoV-2 and, together with ferrets, are able to develop nAbs against the ancestral (B.1), Alpha (B.1.1.7), Beta (B.1.315), Delta (B.1.617.2) and Omicron (BA.1) variants, with lower titres against the latest in dogs and cats, but not in ferrets. Although the prevalence of active SARS-CoV-2 infection measured as direct viral RNA detection was low (0.3%), presence of nAbs in pets living in COVID-19-positive households was relatively high (close to 25% in cats, 10% in dogs and 40% in ferrets). It is essential to continue monitoring SARS-CoV-2 infections in these animals due to their frequent contact with human populations, and we cannot discard the probability of a higher animal susceptibility to new potential SARS-CoV-2 VOCs.
2022-09-27 2022 other research-article; Journal Article abstract-available 10.1111/tbed.14714 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and humoral responses against different variants of concern in domestic pet animals and stray cats from North-Eastern Spain. Fernández-Bastit L, Marfil S, Pradenas E, Valle R, Roca N, Rodon J, Pailler-García L, Trinité B, Parera M, Noguera-Julian M, Martorell J, Izquierdo-Useros N, Carrillo J, Clotet B, Blanco J, Vergara-Alert J, Segalés J. Transbound Emerg Dis. 2022;
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)
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
Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution.
Benet S, Blanch-Lombarte O, Ainsua-Enrich E, Pedreño-Lopez N, [...], Mothe B.
J Infect Dis. 2022; 226 (11)
DOI: 10.1093/infdis/jiac406

Background

We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group).

Methods

This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1-negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined.

Results

At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4-654.9) and 171.9 (61.8-425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145-824) and 555.8 (166.4-1751) BAU/mL in the HIV>500 group and 274.7 (193.7-680.4) and 281.6 (181-831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01).

Conclusions

One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.
2022-11-01 2022 fondo-covid research-article; Journal Article abstract-available 10.1093/infdis/jiac406 Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution. Benet S, Blanch-Lombarte O, Ainsua-Enrich E, Pedreño-Lopez N, Muñoz-Basagoiti J, Raïch-Regué D, Perez-Zsolt D, Peña R, Jiménez E, de la Concepción MLR, Ávila C, Cedeño S, Escribà T, Romero-Martín L, Alarcón-Soto Y, Rodriguez-Lozano GF, Miranda C, González S, Bailón L, Blanco J, Massanella M, Brander C, Clotet B, Paredes R, Esteve M, Izquierdo-Useros N, Carrillo J, Prado JG, Moltó J, Mothe B. J Infect Dis. 2022; 226 (11)
Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.
Giménez E, Albert E, Zulaica J, Torres I, [...], Valencian Vaccine Research Program (ProVaVac) Study Group .
Clin Infect Dis. 2022; 75 (1)
DOI: 10.1093/cid/ciac223
A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.
2022-08-01 2022 other brief-report; Journal Article abstract-available 10.1093/cid/ciac223 Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine. Giménez E, Albert E, Zulaica J, Torres I, Rusu L, Moreno AR, Burgos JS, Peiró S, Salas D, Vanaclocha H, Limón R, Alcaraz MJ, Sánchez-Payá J, Díez-Domingo J, Comas I, Gonzáles-Candelas F, Geller R, Navarro D, Valencian Vaccine Research Program (ProVaVac) Study Group . Clin Infect Dis. 2022; 75 (1)
Editorial: COVID-19 in CNS and PNS: Basic and Clinical Focus on the Mechanisms of Infection and New Tools for the Therapeutic Approach.
Matias-Guiu J, Matias-Guiu JA, Garrido C, Pimienta G, [...], Gomez-Pinedo U.
Front Neurol. 2022; 13
DOI: 10.3389/fneur.2022.838227
2022-03-03 2022 other Editorial 10.3389/fneur.2022.838227 Editorial: COVID-19 in CNS and PNS: Basic and Clinical Focus on the Mechanisms of Infection and New Tools for the Therapeutic Approach. Matias-Guiu J, Matias-Guiu JA, Garrido C, Pimienta G, Reyes PF, Baig AM, Gomez-Pinedo U. Front Neurol. 2022; 13
Point-of-care detection of SARS-CoV-2 antigen among symptomatic vs. asymptomatic persons: Testing for COVID-19 vs. infectivity.
Neukam K, Lucero A, Gutiérrez-Valencia A, Amaya L, [...], Martínez AP.
Front Public Health. 2022; 10
DOI: 10.3389/fpubh.2022.995249

Background

Management of the coronavirus disease 2019 (COVID-19) pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requires rapid and simple methods to detect COVID-19 patients and identify potential infectors. This study aimed to evaluate the utility of a point-of-care (PoC) rapid antigen diagnostic test (Ag-RDT) in these settings.

Patients and methods

Individuals who consecutively presented for SARS-CoV-2 testing at a tertiary care center in Buenos Aires, Argentina, underwent PoC Ag-RDT testing and real-time RT-PCR (qRT-PCR) on the same day during June 2021.

Results

Of 584 included subjects, 108 (18.5%) were symptomatic for COVID-19 while the remaining presented for miscellaneous reasons unrelated to possible or confirmed contact with a SARS-CoV-2-infected individual. A positive Ag-RDT result was obtained in 26 (24.1%) symptomatic and 7 (1.5%) asymptomatic persons (p < 0.001), which was concordant with qRT-PCR in 105/108 [97.2%, Cohen's kappa coefficient (κ) = 0.927] symptomatic and 467/476 (98.1% κ = 0.563) asymptomatic participants, with a positive percentage agreement (PPA; 95% confidence interval) of 89.7% (71.5-97.3%) and 42.9% (18.8-70.4%), respectively. None of the 11 false-negative diagnoses showed a Ct-value ≤20. Considering only failures with a Ct-value below 31 as hypothetical infectivity threshold of 105 SARS-CoV-2 RNA copies/mL, concordance was observed in 98.1% (κ = 0.746) in the asymptomatic population, accounting for a PPA of 66.7% (30.9-91%).

Conclusions

PoC Ag-RDT accurately detected active SARS-CoV-2 infection and showed acceptable diagnostic performance in asymptomatic persons potentially spreading infectious virus. Ag-RDT may therefore be useful to slow down or stop transmission by enabling adequate decisions on isolation at a public health level.
2022-10-17 2022 other Journal Article abstract-available 10.3389/fpubh.2022.995249 Point-of-care detection of SARS-CoV-2 antigen among symptomatic vs. asymptomatic persons: Testing for COVID-19 vs. infectivity. Neukam K, Lucero A, Gutiérrez-Valencia A, Amaya L, Echegoyen N, Martelli A, Videla C, Di Lello FA, Martínez AP. Front Public Health. 2022; 10
Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity.
Cano-Muñoz M, Polo-Megías D, Cámara-Artigas A, Gavira JA, [...], Conejero-Lara F.
Int J Biol Macromol. 2022; 222 (Pt B)
DOI: 10.1016/j.ijbiomac.2022.10.031
SARS-CoV-2 spike (S) protein mediates virus attachment to the cells and fusion between viral and cell membranes. Membrane fusion is driven by mutual interaction between the highly conserved heptad-repeat regions 1 and 2 (HR1 and HR2) of the S2 subunit of the spike. For this reason, these S2 regions are interesting therapeutic targets for COVID-19. Although HR1 and HR2 have been described as transiently exposed during the fusion process, no significant antibody responses against these S2 regions have been reported. Here we designed chimeric proteins that imitate highly stable HR1 helical trimers and strongly bind to HR2. The proteins have broad inhibitory activity against WT B.1 and BA.1 viruses. Sera from COVID-19 convalescent donors showed significant levels of reactive antibodies (IgG and IgA) against the HR1 mimetic proteins, whereas these antibody responses were absent in sera from uninfected donors. Moreover, both inhibitory activity and antigenicity of the proteins correlate positively with their structural stability but not with the number of amino acid changes in their HR1 sequences, indicating a conformational and conserved nature of the involved epitopes. Our results reveal previously undetected spike epitopes that may guide the design of new robust COVID-19 vaccines and therapies.
2022-10-08 2022 other research-article; Journal Article abstract-available 10.1016/j.ijbiomac.2022.10.031 Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity. Cano-Muñoz M, Polo-Megías D, Cámara-Artigas A, Gavira JA, López-Rodríguez MJ, Laumond G, Schmidt S, Demiselle J, Bahram S, Moog C, Conejero-Lara F. Int J Biol Macromol. 2022; 222 (Pt B)
COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences.
Martínez-Salazar B, Holwerda M, Stüdle C, Piragyte I, [...], Döring Y.
Front Cell Dev Biol. 2022; 10
DOI: 10.3389/fcell.2022.824851
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as "Long-COVID-syndrome". Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.
2022-02-15 2022 other review-article; Review; Journal Article abstract-available 10.3389/fcell.2022.824851 COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences. Martínez-Salazar B, Holwerda M, Stüdle C, Piragyte I, Mercader N, Engelhardt B, Rieben R, Döring Y. Front Cell Dev Biol. 2022; 10
Mountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study.
Gvozdjáková A, Sumbalová Z, Kucharská J, Rausová Z, [...], Palacka P.
Environ Sci Pollut Res Int. 2022;
DOI: 10.1007/s11356-022-22949-2
European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR - mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16-18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome.
2022-09-23 2022 other research-article; Journal Article abstract-available 10.1007/s11356-022-22949-2 Mountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study. Gvozdjáková A, Sumbalová Z, Kucharská J, Rausová Z, Kovalčíková E, Takácsová T, Navas P, López-Lluch G, Mojto V, Palacka P. Environ Sci Pollut Res Int. 2022;
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)
Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells.
Icho S, Rujas E, Muthuraman K, Tam J, [...], Melnyk RA.
Antimicrob Agents Chemother. 2022; 66 (7)
DOI: 10.1128/aac.00439-22
An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using nonspecific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high-throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS-CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways.
2022-06-15 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/aac.00439-22 Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells. Icho S, Rujas E, Muthuraman K, Tam J, Liang H, Landreth S, Liao M, Falzarano D, Julien JP, Melnyk RA. Antimicrob Agents Chemother. 2022; 66 (7)
Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.
Kim MS, Seong D, Li H, Chung SK, [...], Smith L.
Rev Med Virol. 2022; 32 (5)
DOI: 10.1002/rmv.2336
The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
2022-02-26 2022 other Meta-Analysis; Systematic Review; review-article; Review; Journal Article abstract-available 10.1002/rmv.2336 Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis. Kim MS, Seong D, Li H, Chung SK, Park Y, Lee M, Lee SW, Yon DK, Kim JH, Lee KH, Solmi M, Dragioti E, Koyanagi A, Jacob L, Kronbichler A, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Radua J, Oh H, Kostev K, Ogino S, Lee IM, Giovannucci E, Barnett Y, Butler L, McDermott D, Ilie PC, Shin JI, Smith L. Rev Med Virol. 2022; 32 (5)
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 IM; 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)
[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)
Fuzzy-Based PROMETHEE Method for Performance Ranking of SARS-CoV-2 IgM Antibody Tests
Arikan A, Sanlidag T, Sayan M, Uzun B, [...], Uzun Ozsahin D.
Diagnostics (Basel). 2022; 12 (11)
DOI:
Antibody tests, widely used as a complementary approach to reverse transcriptase–polymerase chain reaction testing in identifying COVID-19 cases, are used to measure antibodies developed for COVID-19. This study aimed to evaluate the different parameters of the FDA-authorized SARS-CoV-2 IgM antibody tests and to rank them according to their performance levels. In the study, we involved 27 antibody tests, and the analyzes were performed using the fuzzy preference ranking organization method for the enrichment evaluation model, a multi-criteria decision-making model. While criteria such as analytical sensitivity, specificity, positive predictive value, and negative predictive value were evaluated in the study, the ranking was reported by determining the importance levels of the criteria. According to our evaluation, Innovita 2019-nCoV Ab Test (colloidal gold) was at the top of the ranking. While Cellex qSARS-CoV-2 IgG/IgM Rapid Test and Assure COVID-19 IgG/IgM Rapid Tester ranked second and third on the list, the InBios-SCoV 2 Detect Ig M ELISA Rapid Test Kit was determined as the least preferable. The fuzzy preference ranking organization method for enrichment evaluation, which has been applied to many fields, can help decision-makers choose the appropriate antibody test for managing COVID-19 in controlling the global pandemic.
2022-11-01 2022 other research-article; Journal Article abstract-available Fuzzy-Based PROMETHEE Method for Performance Ranking of SARS-CoV-2 IgM Antibody Tests Arikan A, Sanlidag T, Sayan M, Uzun B, Uzun Ozsahin D. Diagnostics (Basel). 2022; 12 (11)
Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition.
Fernández-de-Las-Peñas C, Nijs J, Neblett R, Polli A, [...], Arendt-Nielsen L.
Biomedicines. 2022; 10 (10)
DOI: 10.3390/biomedicines10102562
Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.
2022-10-13 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10102562 Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition. Fernández-de-Las-Peñas C, Nijs J, Neblett R, Polli A, Moens M, Goudman L, Shekhar Patil M, Knaggs RD, Pickering G, Arendt-Nielsen L. Biomedicines. 2022; 10 (10)
A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.
Pérez P, Lázaro-Frías A, Zamora C, Sánchez-Cordón PJ, [...], García-Arriaza J.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.824728
We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.
2022-01-27 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2021.824728 A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection. Pérez P, Lázaro-Frías A, Zamora C, Sánchez-Cordón PJ, Astorgano D, Luczkowiak J, Delgado R, Casasnovas JM, Esteban M, García-Arriaza J. Front Immunol. 2021; 12
Persistent COVID-19 symptoms 1 year after hospital discharge: A prospective multicenter study.
Aranda J, Oriol I, Feria L, Abelenda G, [...], Carratalà J.
PLoS One. 2022; 17 (10)
DOI: 10.1371/journal.pone.0275615

Objective

To determine the health status and exercise capacity of COVID-19 survivors one year after hospital discharge.

Methods

This multicenter prospective study included COVID-19 survivors 12 months after hospital discharge. Participants were randomly selected from a large cohort of COVID-19 patients who had been hospitalized until 15th April 2020. They were interviewed about persistent symptoms, underwent a physical examination, chest X-ray, and a 6-minute walk test (6MWT). A multivariate analysis was performed to determine the risk factors for persistent dyspnea.

Results

Of the 150 patients included, 58% were male and the median age was 63 (IQR 54-72) years. About 82% reported ≥1 symptoms and 45% had not recovered their physical health. The multivariate regression analysis revealed that the female sex, chronic obstructive pulmonary disease, and smoking were independent risk factors for persistent dyspnea. Approximately 50% completed less than 80% of the theoretical distance on the 6MWT. Only 14% had an abnormal X-ray, showing mainly interstitial infiltrates. A third of them had been followed up in outpatient clinics and 6% had undergone physical rehabilitation.

Conclusion

Despite the high rate of survivors of the first wave of the COVID-19 pandemic with persistent symptomatology at 12 months, the follow-up and rehabilitation of these patients has been really poor. Studies focusing on the role of smoking in the persistence of COVID-19 symptoms are lacking.
2022-10-10 2022 other research-article; Multicenter Study; Journal Article abstract-available 10.1371/journal.pone.0275615 Persistent COVID-19 symptoms 1 year after hospital discharge: A prospective multicenter study. Aranda J, Oriol I, Feria L, Abelenda G, Rombauts A, Simonetti AF, Catalano C, Pallarès N, Martín M, Vàzquez N, Vall-Llosera E, Rhyman N, Suárez RC, Nogué M, Loureiro-Amigo J, Coloma A, Ceresuela L, Carratalà J. PLoS One. 2022; 17 (10)
Case report: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion.
Daviña-Nuñez C, Pérez-Castro S, Martínez-Lamas L, Cabrera-Alvargonzález JJ, [...], Regueiro-García B.
Virol J. 2022; 19 (1)
DOI: 10.1186/s12985-022-01883-2

Background

SARS-CoV-2 variant tracking is key to the genomic surveillance of the COVID-19 pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification.

Case presentation

A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike amino acids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation.

Conclusions

To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the probe target area of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.
2022-10-27 2022 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report abstract-available 10.1186/s12985-022-01883-2 Case report: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion. Daviña-Nuñez C, Pérez-Castro S, Martínez-Lamas L, Cabrera-Alvargonzález JJ, Rey-Cao S, Carballo-Fernandez R, Godoy-Diz M, López-Bóveda L, Del Campo-Pérez V, Suárez-Luque S, Regueiro-García B. Virol J. 2022; 19 (1)
Myocardial Injuries in COVID-19: More Questions Than Answers.
Bardaji A.
J Clin Med. 2022; 11 (15)
DOI: 10.3390/jcm11154527
At the end of 2019, the SARS-CoV-2 virus was reported to be responsible for the cases of pneumonia that had begun to appear a few months earlier in the Wuhan province of China [...].
2022-08-03 2022 other Editorial abstract-available 10.3390/jcm11154527 Myocardial Injuries in COVID-19: More Questions Than Answers. Bardaji A. J Clin Med. 2022; 11 (15)
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 IM; 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)
Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment.
Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, [...], Rodriguez-Perez AI.
Biomedicines. 2022; 10 (2)
DOI: 10.3390/biomedicines10020502
A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.
2022-02-21 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10020502 Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment. Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, Quijano A, Rodriguez-Perez AI. Biomedicines. 2022; 10 (2)
Acute bronchiolitis during the COVID-19 pandemic Bronquiolitis aguda durante la pandemia de COVID-19
Flores-Pérez P, Gerig N, Cabrera-López M, de Unzueta-Roch J, [...], Calvo C.
Enferm Infecc Microbiol Clin (Engl Ed). 2022; 40 (10)
DOI:

Introduction

The autumn and winter bronchiolitis epidemics have virtually disappeared in the first year of the COVID-19 pandemic. Our objectives were characterised bronchiolitis during fourth quarter of 2020 and the role played by SARS-CoV-2.

Methods

Prospective multi-centre study performed in Madrid (Spain) between October and December 2020 including all children admitted with acute bronchiolitis. Clinical data were collected and multiplex PCR for respiratory viruses were performed.

Results

Thirty-three patients were hospitalised with bronchiolitis during the study period: 28 corresponded to rhinovirus (RV), 4 to SARS-CoV-2, and 1 had both types of infection. SAR-CoV-2 bronchiolitis were comparable to RV bronchiolitis except for a shorter hospital stay. A significant decrease in the admission rate for bronchiolitis was found and no RSV was isolated.

Conclusion

SARS-CoV-2 infection rarely causes acute bronchiolitis and it is not associated with a severe clinical course. During COVID-19 pandemic period there was a marked decrease in bronchiolitis cases.
2022-12-01 2022 other research-article; Journal Article abstract-available Acute bronchiolitis during the COVID-19 pandemic Bronquiolitis aguda durante la pandemia de COVID-19 Flores-Pérez P, Gerig N, Cabrera-López M, de Unzueta-Roch J, del Rosal T, Calvo C. Enferm Infecc Microbiol Clin (Engl Ed). 2022; 40 (10)
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)
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)
Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination.
Esparcia-Pinedo L, Yarci-Carrión A, Mateo-Jiménez G, Ropero N, [...], Alfranca A.
Clin Infect Dis. 2022;
DOI: 10.1093/cid/ciac590

Background

Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to COVID-19 and may impair the generation of protective immunity after vaccine administration.

Methods

The cellular and humoral responses of 55 DS patients who received a complete SARS-CoV-2 vaccination regime at one to three (V1) and six (V2) months were characterized.

Results

SARS-CoV-2-reactive CD4 + and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase of SARS-CoV-2-specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes were already observed at V1 after vaccine administration. Specific IgG antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, though IgG titers decreased significantly between both timepoints.

Conclusions

Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination.
2022-07-23 2022 other research-article; Journal Article abstract-available 10.1093/cid/ciac590 Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination. Esparcia-Pinedo L, Yarci-Carrión A, Mateo-Jiménez G, Ropero N, Gómez-Cabañas L, Lancho-Sánchez Á, Almendro-Vázquez P, Martín-Gayo E, Paz-Artal E, Sanchez-Madrid F, Moldenhauer F, Gutiérrez-Cobos A, de Asúa DR, Alfranca A. Clin Infect Dis. 2022;
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;
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
Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants
Wirnsberger G, Monteil V, Eaton B, Postnikova E, [...], Penninger JM.
bioRxiv; 2021.
DOI: 10.1101/2021.09.10.459744
The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is therefore paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, and Delta, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by multiple VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.
2021-09-10 2021 other Preprint abstract-available 10.1101/2021.09.10.459744 Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants Wirnsberger G, Monteil V, Eaton B, Postnikova E, Murphy M, Braunsfeld B, Crozier I, Kricek F, Niederhöfer J, Schwarzböck A, Breid H, Sanchez Jimenez A, Bugajska-Schretter A, Dohnal A, Ruf C, Gugenberger R, Hagelkruys A, Montserrat N, Holbrook MR, Oostenbrink C, Shoemaker RH, Mirazimi A, Penninger JM. bioRxiv; 2021.
Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.
García-García I, Seco-Meseguer E, Ruiz-Seco P, Navarro-Jimenez G, [...], Borobia AM.
J Clin Med. 2022; 11 (4)
DOI: 10.3390/jcm11041139
We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.
2022-02-21 2022 other research-article; Journal Article abstract-available 10.3390/jcm11041139 Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial. García-García I, Seco-Meseguer E, Ruiz-Seco P, Navarro-Jimenez G, Martínez-Porqueras R, Espinosa-Díaz M, Ortega-Albás JJ, Sagastagoitia I, García-Morales MT, Jiménez-González M, Martínez de Soto L, Bajo-Martínez AI, Del Palacio-Tamarit M, López-García R, Díaz-García L, Queiruga-Parada J, Giesen C, Pérez-Villena A, de Castro-Martínez M, González-García JJ, Rodriguez-Rubio M, de la Oliva P, Arribas JR, Carcas AJ, Borobia AM. J Clin Med. 2022; 11 (4)
Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review.
Saegeman V, Cohen MC, Abasolo L, Rello J, [...], Fernandez-Rodriguez A.
Ann Transl Med. 2022; 10 (11)
DOI: 10.21037/atm-22-605

Background and objective

A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings.

Methods

A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021.

Key content and findings

Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage-including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48-19.62), fibrosis (OR =3.88, 95% CI: 1.25-12.08), vascular damage (OR =5.49, 95% CI: 1.78-16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04-23.97).

Conclusions

We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation.
2022-06-01 2022 other review-article; Review; Journal Article abstract-available 10.21037/atm-22-605 Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review. Saegeman V, Cohen MC, Abasolo L, Rello J, Fernandez-Gutierrez B, Fernandez-Rodriguez A. Ann Transl Med. 2022; 10 (11)
Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms.
Toledano JM, Moreno-Fernandez J, Puche-Juarez M, Ochoa JJ, [...], Diaz-Castro J.
Antioxidants (Basel). 2021; 11 (1)
DOI: 10.3390/antiox11010005
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 10.3390/antiox11010005 Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms. Toledano JM, Moreno-Fernandez J, Puche-Juarez M, Ochoa JJ, Diaz-Castro J. Antioxidants (Basel). 2021; 11 (1)
Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor.
Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso AM, Revenga-Parra M, [...], Lorenzo E.
Talanta. 2022; 247
DOI: 10.1016/j.talanta.2022.123543
Given the great utility that having fast, efficient and cost-effective methods for the detection of SARS-CoV-2 in wastewater can have in controlling the pandemic caused by this virus, the development of new dependable and specific SARS-CoV-2 coronavirus sensing devices to be applied to wastewater is essential to promote public health interventions. Therefore, herein we propose a new method to detect SARS-CoV-2 in wastewater based on a carbon nanodots-amplified electrochemiluminescence immunosensor for the determination of the SARS-CoV-2 Spike S1 protein. For the construction of the immunosensor, N-rich carbon nanodots have been synthetized with a double function: to contribute as amplifiers of the electrochemiluminescent signal in presence of [Ru(bpy)3]2+ and as antibody supports by providing functional groups capable of covalently interacting with the SARS-CoV-2 Spike S1 antibody. The proposed ECL immunosensor has demonstrated a high specificity in presence of other virus-related proteins and responded linearly to SARS-CoV-2 Spike S1 concentration over a wide range with a limit of detection of 1.2 pg/mL. The immunosensor has an excellent stability and achieved the detection of SARS-CoV-2 Spike S1 in river and urban wastewater, which supplies a feasible and reliable sensing platform for early virus detection and therefore to protect the population. The detection of SARS-CoV-2 Spike S1 in urban wastewater can be used as a tool to measure the circulation of the virus in the population and to detect a possible resurgence of COVID-19.
2022-05-13 2022 other research-article; Journal Article abstract-available 10.1016/j.talanta.2022.123543 Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor. Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso AM, Revenga-Parra M, Pariente F, Lorenzo E. Talanta. 2022; 247
Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID.
Goh D, Lim JCT, Fernaíndez SB, Joseph CR, [...], Yeong JPS.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.939989
The World Health Organization has defined long COVID-19 (LC) as a condition that occurs in individuals with a history of SARS-CoV-2 infection who exhibit persistent symptoms after its acute phase that last for at least two months and cannot be explained by an alternative diagnosis. Since we had previously reported residual viral antigens in tissues of convalescent patients, we aimed to assess the presence of such antigens in long COVID tissues. Here, we established the presence of the residual virus in the appendix, skin, and breast tissues of 2 patients who exhibited LC symptoms 163 and 426 days after symptom onset. With multiplex immunohistochemistry, we detected viral nucleocapsid protein in all three tissues. The nucleocapsid protein was further observed to colocalize with macrophage marker CD68, suggesting that immune cells were direct targets of SARS-CoV-2. Additionally, using RNAscope, the presence of viral RNA was also detected. Our positive finding in the breast tissue is corroborated by the recent reports of immunocompromised patients experiencing LC symptoms and persistent viral replication. Overall, our findings and emerging LC studies raise the possibility that the gastrointestinal tract may function as a reservoir for SARS-CoV-2.
2022-09-05 2022 other Research Support, Non-U.S. Gov't; Case Reports; case-report abstract-available 10.3389/fimmu.2022.939989 Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID. Goh D, Lim JCT, Fernaíndez SB, Joseph CR, Edwards SG, Neo ZW, Lee JN, Caballero SG, Lau MC, Yeong JPS. Front Immunol. 2022; 13
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
New insights into antibody levels against SARS-CoV-2 for healthcare personnel vaccinated with tozinameran (Comirnaty).
Fernández-Suárez A, Jiménez Coronado R, Clavijo Aroca C, Navarro Martín E, [...], Díaz-Iglesias JM.
PLoS One. 2022; 17 (11)
DOI: 10.1371/journal.pone.0276968

Aim

The aim of this study is to determine the levels of spike protein IgG and total antibodies in subjects vaccinated against SARS-CoV-2 (both infected and non-infected) and the titer evolution over time. In addition, we also addressed the performance of each of the included platforms in the study, as they are intended to measure antibody levels in naturally infected patients.

Materials and methods

An observational study including 288 volunteer healthcare professionals vaccinated against SARS-CoV-2 (Comirnaty™) at the Andújar Alto Guadalquivir Hospital. Serum samples were obtained in September 2020 and 14 and 90 days after administration of the second dose. The following in vitro methods were used: Elecsys Anti-SARS-CoV-2 N and Elecsys Anti-SARS-CoV-2 S (Roche, Germany) and EliA SARS-CoV-2-Sp1 IgG (Thermo Fisher Scientific, Germany).

Results

For the Elecsys S method at 1/10 dilution and for the EliA Sp1 IgG method at 1/5 dilution, 54% and 19% of samples were out of range, respectively. The vaccine activated a high humoral response- 0 to 3000 BAU/mL being the "normal titer range" in all volunteers. Patients vaccinated after COVID-19 exhibited higher total S antibody load values than non-vaccinated volunteers while showing the same response for S IgG isotype. Titers decreased up to 86% in the case of S IgG neutralizing antibodies.

Conclusions

The characterization of human response to SARS-CoV-2 vaccines is still far from being completely elucidated. It is important to increase the methods dynamic range to study humoral response evolution in depth and decide whether booster doses or seasonal vaccination plans will be necessary to definitively control the pandemic.
2022-11-03 2022 other research-article; Journal Article; Observational Study abstract-available 10.1371/journal.pone.0276968 New insights into antibody levels against SARS-CoV-2 for healthcare personnel vaccinated with tozinameran (Comirnaty). Fernández-Suárez A, Jiménez Coronado R, Clavijo Aroca C, Navarro Martín E, Qmega Qmega A, Díaz-Iglesias JM. PLoS One. 2022; 17 (11)
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)
MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters.
Boudewijns R, Pérez P, Lázaro-Frías A, Van Looveren D, [...], García-Arriaza J.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.845969
To control the coronavirus disease 2019 (COVID-19) pandemic and the emergence of different variants of concern (VoCs), novel vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed. In this study, we report the potent immunogenicity and efficacy induced in hamsters by a vaccine candidate based on a modified vaccinia virus Ankara (MVA) vector expressing a human codon optimized full-length SARS-CoV-2 spike (S) protein (MVA-S). Immunization with one or two doses of MVA-S elicited high titers of S- and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against parental SARS-CoV-2 and VoC alpha, beta, gamma, delta, and omicron. After SARS-CoV-2 challenge, MVA-S-vaccinated hamsters showed a significantly strong reduction of viral RNA and infectious virus in the lungs compared to the MVA-WT control group. Moreover, a marked reduction in lung histopathology was also observed in MVA-S-vaccinated hamsters. These results favor the use of MVA-S as a potential vaccine candidate for SARS-CoV-2 in clinical trials.
2022-03-16 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.845969 MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters. Boudewijns R, Pérez P, Lázaro-Frías A, Van Looveren D, Vercruysse T, Thibaut HJ, Weynand B, Coelmont L, Neyts J, Astorgano D, Montenegro D, Puentes E, Rodríguez E, Dallmeier K, Esteban M, García-Arriaza J. Front Immunol. 2022; 13
Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis
Lind M, Robertson A, Silva J, Warner F, [...], Schulz W.
PLoS Med. 2022; 19 (12)
DOI:

Background

The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co