Epigenome-wide association study of COVID-19 severity with respiratory failure
Castro de Moura, Manuel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Davalos, Veronica (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Planas-Serra, Laura (Institut d'Investigació Biomèdica de Bellvitge)
Álvarez-Errico, Damiana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Arribas, Carles (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ruiz, Montserrat (Institut d'Investigació Biomèdica de Bellvitge)
Aguilera-Albesa, Sergio (Complejo Hospitalario de Navarra)
Troya, Jesús (Hospital Universitario Infanta Leonor)
Valencia Ramos, Juan (Hospital Universitario de Burgos)
Vélez Santamaria, Valentina (Hospital Universitari de Bellvitge)
Rodríguez-Palmero, Agustí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Villar Garcia, Judit (Institut Hospital del Mar d'Investigacions Mèdiques)
Horcajada, Juan Pablo (Institut Hospital del Mar d'Investigacions Mèdiques)
Albu, Sergiu (Institut Guttmann Foundation. Badalona)
Casasnovas, Carlos (Hospital Universitari de Bellvitge)
Rull, Anna (Hospital Universitari Joan XXIII de Tarragona)
Reverté Calvet, Laia (Hospital Universitari Joan XXIII de Tarragona)
Dietl, Beatriz (Servei de malalties infeccioses Hospital Universitari MutuaTerrassa. Universitat de Barcelona)
Dalmau, David (Universitat de Barcelona. Hospital Mútua de Terrassa)
Arranz, María Jesús (Fundació Docència i Recerca Mútua Terrassa)
Llucià-Carol, Laia (Stroke Pharmacogenomics and Genetics Group. Sant Pau Institute of Research. Sant Pau Hospital)
Planas, Anna Maria (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Pérez-Tur, Jordi (Institut de Biomedicina de València-CSIC. CIBERNED. Unitat Mixta de Neurologia i Genètica)
Fernandez-Cadenas, Israel (Stroke Pharmacogenomics and Genetics Group. Sant Pau Institute of Research. Sant Pau Hospital)
Villares, Paula (Hospital Universitario HM Sanchinarro (Madrid))
Tenorio, Jair (Center for Biomedical Research on Rare Diseases (CIBERER). ISCIII)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martín-Nalda, Andrea (Hospital Universitari Vall d'Hebron)
Soler-Palacín, Pere (Hospital Universitari Vall d'Hebron)
Vidal, Francesc (Hospital Universitari Joan XXIII de Tarragona)
Pujol, Aurora 1968- (Institució Catalana de Recerca i Estudis Avançats)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2021
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.
Note:	Fundació Carreras
Note:	We thank the Health Department and Centres de Recerca de Catalunya (CERCA) Programme of the Generalitat de Catalunya, the Josep Carreras Leukaemia Foundation and the Cellex Foundation for institutional support.
Note:	Dr. Esteller reports grants from Ferrer International, personal fees from Quimatryx, outside the submitted work. The other authors declare no conflicts of interest.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Coronavirus ; SARS-CoV-2 ; COVID-19 ; Epigenetics ; DNA methylation
Published in:	EBioMedicine, Vol. 66 (april 2021) , p. 103339, ISSN 2352-3964

DOI: 10.1016/j.ebiom.2021.103339
PMID: 33867313

10 p, 1.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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