Epigenome-wide association study of COVID-19 severity with respiratory failure

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• dc.contributor.author Castro de Moura, Manuel
• dc.contributor.author Villar García, Judit
• dc.contributor.author Horcajada Gallego, Juan Pablo
• dc.contributor.author Esteller, Manel
• dc.date.accessioned 2021-09-13T07:37:25Z
• dc.date.available 2021-09-13T07:37:25Z
• dc.date.issued 2021
• dc.description.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. Funding: The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Castro de Moura M, Davalos V, Planas-Serra L, Alvarez-Errico D, Arribas C, Ruiz M et al. Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine. 2021;66:103339. DOI: 10.1016/j.ebiom.2021.103339
• dc.identifier.doi http://dx.doi.org/10.1016/j.ebiom.2021.103339
• dc.identifier.issn 2352-3964
• dc.identifier.uri http://hdl.handle.net/10230/48436
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof EBioMedicine. 2021;66:103339
• dc.rights © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword COVID-19
• dc.subject.keyword Coronavirus
• dc.subject.keyword DNA methylation
• dc.subject.keyword Epigenetics
• dc.subject.keyword SARS-CoV-2
• dc.title Epigenome-wide association study of COVID-19 severity with respiratory failure
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion