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http://hdl.handle.net/2445/177779
Title: | Epigenome-wide association study of COVID-19 severity with respiratory failure |
Author: | Castro de Moura, Manuel Davalos, Veronica Planas Serra, Laura Alvarez Errico, Damiana Arribas, Carles Ruiz, Montserrat Aguilera Albesa, Sergio Troya, Jesús Valencia Ramos, Juan Vélez Santamaria, Valentina Rodríguez Palmero, Agustí Villar García, Judit Horcajada, Juan Pablo Albu, Sergiu Casasnovas Pons, Carlos Rull, Anna Reverte, Laia Dietl, Beatriz Dalmau, David Arranz, Maria J. Llucià-carol, Laia Planas, Anna M. Pérez Tur, Jordi Fernández Cadenas, Israel Villares, Paula Tenorio, Jair Colobran, Roger Martin Nalda, Andrea Soler Palacín, Pere Vidal, Francesc Pujol Onofre, Aurora Esteller, Manel |
Keywords: | COVID-19 SARS-CoV-2 Epigenètica Insuficiència respiratòria COVID-19 SARS-CoV-2 Epigenetics Respiratory insufficiency |
Issue Date: | 1-Apr-2021 |
Publisher: | Elsevier B. V. |
Abstract: | Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2021.103339 |
It is part of: | EBioMedicine, 2021, vol. 66 |
URI: | http://hdl.handle.net/2445/177779 |
Related resource: | https://doi.org/10.1016/j.ebiom.2021.103339 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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