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

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 s...

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Detalles Bibliográficos
Autores: de Moura, MC, Davalos, V, Planas-Serra, L, Alvarez-Errico, D, Arribas, C, Ruiz, M, Aguilera-Albesa, S, Troya, J, Valencia-Ramos, J, Velez-Santamaria, V, Rodriguez-Palmero, A, Villar-Garcia, J, Horcajada, JP, Albu, S, Casasnovas, C, Rull, A, Reverte, L, Dietl, B, Dalmau, D, Arranz, MJ, Llucia-Carol, L, Planas, AM, Perez-Tur, J, Fernandez-Cadenas, I, Villares, P, Tenorio, J, Colobran, R, Martin-Nalda, A, Soler-Palacin, P, Vidal, F, Pujol, A, Esteller, M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4823
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4823
Access Level:acceso abierto
Palabra clave:Coronavirus
SARS-CoV-2
COVID-19
Epigenetics
DNA methylation
Descripción
Sumario: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.

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