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

Identifier:  imarina:9216710

Handle: https://hdl.handle.net/20.500.11797/imarina9216710

Authors:  de Moura, MC; Davalos, V; Planas-Serra, L; Alvarez-Errico, D; Arribas, C; Ruiz, M; Aguilera-Albesa, S; Troya, J; Valencia-Ramos, J; Vélez-Santamaria, V; Rodríguez-Palmero, A; Villar-Garcia, J; Horcajada, JP; Albu, S; Casasnovas, C; Rull, A; Reverte, L; Dietl, B; Dalmau, D; Arranz, MJ; Llucià-Carol, L; Planas, AM; Pérez-Tur, J; Fernandez-Cadenas, I; Villares, P; Tenorio, J; Colobran, R; Martin-Nalda, A; Soler-Palacin, P; Vidal, F; Pujol, A; Esteller, M

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 hospitaliza-tion 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) candi-dates, 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. (C) 2021 The Authors. Published by Elsevier B.V.