Epigenome-wide association study of COVID-19 severity with respiratory failure
Por:
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
Publicada:
1 abr 2021
Ahead of Print:
1 abr 2021
Resumen:
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.
Filiaciones:
de Moura, MC:
Josep Carreras Leukaemia Res Inst IJC, Barcelona 08916, Catalonia, Spain
Davalos, V:
Josep Carreras Leukaemia Res Inst IJC, Barcelona 08916, Catalonia, Spain
Planas-Serra, L:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
Alvarez-Errico, D:
Josep Carreras Leukaemia Res Inst IJC, Barcelona 08916, Catalonia, Spain
Arribas, C:
Josep Carreras Leukaemia Res Inst IJC, Barcelona 08916, Catalonia, Spain
Ruiz, M:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
Aguilera-Albesa, S:
Navarra Hlth Serv Hosp, Pamplona, Spain
Troya, J:
Infanta Leonor Univ Hosp, Madrid, Spain
Valencia-Ramos, J:
Univ Hosp Burgos, Burgos, Spain
Velez-Santamaria, V:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
Bellvitge Univ Hosp, Barcelona, Catalonia, Spain
Rodriguez-Palmero, A:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
Univ Hosp Germans Trias & Pujol, Barcelona, Catalonia, Spain
Villar-Garcia, J:
Hosp del Mar IMIM Biomed Res Inst, Barcelona, Catalonia, Spain
Horcajada, JP:
Hosp del Mar IMIM Biomed Res Inst, Barcelona, Catalonia, Spain
Albu, S:
Inst Guttmann Fdn, Barcelona, Catalonia, Spain
Casasnovas, C:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
Bellvitge Univ Hosp, Barcelona, Catalonia, Spain
Rull, A:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, Tarragona, Catalonia, Spain
Reverte, L:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, Tarragona, Catalonia, Spain
Dietl, B:
Univ Barcelona, Serv Malalties Infeccioses Hosp Univ MutuaTerrass, Barcelona, Catalonia, Spain
Dalmau, D:
Univ Barcelona, HIV AIDS Unit Hosp Univ MutuaTerrassa, MutuaTerrassa Res & Innovat Fdn, Barcelona, Catalonia, Spain
Arranz, MJ:
Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Catalonia, Spain
Hosp Univ Mutua Terrassa, Barcelona, Catalonia, Spain
Llucia-Carol, L:
St Pau Hosp, St Pau Inst Res, Stroke Pharmacogen & Genet Grp, Barcelona, Catalonia, Spain
Planas, AM:
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inst Invest Biomed Barcelona IIBB, Dept Brain Ischem & Neurodegenerat, CSIC,Area Neurosci, Barcelona, Catalonia, Spain
Perez-Tur, J:
IIS La Fe, Inst Biomed Valencia CSIC, Unitat Mixta Neurol & Genet, CIBERNED, Vallencia, Spain
Fernandez-Cadenas, I:
St Pau Hosp, St Pau Inst Res, Stroke Pharmacogen & Genet Grp, Barcelona, Catalonia, Spain
Villares, P:
Hosp HM Sanchinarro, HM Hosp, Internal Med Dept, Madrid, Spain
Tenorio, J:
Hosp Univ La Paz, INGEMM Inst Genet Med & Mol, Madrid, Spain
ISCIII, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Colobran, R:
UAB, Hosp Univ Vall dHebron, Immunol Div, Vall dHebron Res Inst,Genet Dept, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Martin-Nalda, A:
Hosp Univ Vall dHebron, Pediat Infect Dis & Immunodeficiencies Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Soler-Palacin, P:
Hosp Univ Vall dHebron, Pediat Infect Dis & Immunodeficiencies Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Vidal, F:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, Tarragona, Catalonia, Spain
Pujol, A:
Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain
ISCIII, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Catalonia, Spain
Esteller, M:
Josep Carreras Leukaemia Res Inst IJC, Barcelona 08916, Catalonia, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Catalonia, Spain
Univ Barcelona UB, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Catalonia, Spain
Green Published, gold
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