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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • 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
  • 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.

Datos de la publicación

ISSN/ISSNe:
2352-3964, 2352-3964

Ebiomedicine  ELSEVIER SCIENCE BV

Tipo:
Article
Páginas:
103339-103339
Factor de Impacto:
2,663 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 81

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Keywords

  • Coronavirus; SARS-CoV-2; COVID-19; Epigenetics; DNA methylation

Proyectos asociados

COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014

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