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Title

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

AuthorsCastro de Moura, Manuel; Davalos, Veronica; Planas-Serra, Laura; Álvarez-Errico, Damiana; Arribas, Carles; Ruiz, Montserrat; Aguilera-Albesa, Sergio; Troya, Jesús; Valencia-Ramos, Juan; Vélez-Santamaría, Valentina; Rodríguez-Palmero, Agustí; Villar-García, Judit; Horcajada, Juan Pablo; Albu, Sergiu; Casasnovas, Carlos; Rull, Anna; Reverté, Laia; Dietl, Beatriz; Dalmau, David; Arranz, Maria J.; Llucià-Carol, Laia; Planas, Anna M. CSIC ORCID; Pérez-Tur, Jordi CSIC ORCID CVN ; Fernández-Cadenas, Israel; Villares, Paula; Tenorio, Jair; Colobran, Roger; Martin-Nalda, Andrea; Soler-Palacín, Pere; Vidal, Francesc; Pujol, Aurora; Esteller, Manel
KeywordsCoronavirus
SARS-CoV-2
COVID-19
Epigenetics
DNA methylation
Issue Date17-Apr-2021
PublisherElsevier BV
CitationEBioMedicine 103339 (2021)
AbstractBackground: 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.
Publisher version (URL)https://doi.org/10.1016/j.ebiom.2021.103339
URIhttp://hdl.handle.net/10261/239354
DOI10.1016/j.ebiom.2021.103339
E-ISSN2352-3964
Appears in Collections:(VICYT) Colección Especial COVID-19
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(IBV) Artículos

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