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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Format: | Article |
Language: | English |
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Elsevier
2021-04-01
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Series: | EBioMedicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421001328 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Manuel Castro de Moura Veronica Davalos Laura Planas-Serra Damiana Alvarez-Errico Carles Arribas Montserrat Ruiz Sergio Aguilera-Albesa Jesús Troya Juan Valencia-Ramos Valentina Vélez-Santamaria Agustí Rodríguez-Palmero Judit Villar-Garcia Juan P. Horcajada Sergiu Albu Carlos Casasnovas Anna Rull Laia Reverte Beatriz Dietl David Dalmau Maria J. Arranz Laia Llucià-Carol Anna M. Planas Jordi Pérez-Tur Israel Fernandez-Cadenas Paula Villares Jair Tenorio Roger Colobran Andrea Martin-Nalda Pere Soler-Palacin Francesc Vidal Aurora Pujol Manel Esteller |
spellingShingle |
Manuel Castro de Moura Veronica Davalos Laura Planas-Serra Damiana Alvarez-Errico Carles Arribas Montserrat Ruiz Sergio Aguilera-Albesa Jesús Troya Juan Valencia-Ramos Valentina Vélez-Santamaria Agustí Rodríguez-Palmero Judit Villar-Garcia Juan P. Horcajada Sergiu Albu Carlos Casasnovas Anna Rull Laia Reverte Beatriz Dietl David Dalmau Maria J. Arranz Laia Llucià-Carol Anna M. Planas Jordi Pérez-Tur Israel Fernandez-Cadenas Paula Villares Jair Tenorio Roger Colobran Andrea Martin-Nalda Pere Soler-Palacin Francesc Vidal Aurora Pujol Manel Esteller Epigenome-wide association study of COVID-19 severity with respiratory failure EBioMedicine Coronavirus SARS-CoV-2 COVID-19 Epigenetics DNA methylation |
author_facet |
Manuel Castro de Moura Veronica Davalos Laura Planas-Serra Damiana Alvarez-Errico Carles Arribas Montserrat Ruiz Sergio Aguilera-Albesa Jesús Troya Juan Valencia-Ramos Valentina Vélez-Santamaria Agustí Rodríguez-Palmero Judit Villar-Garcia Juan P. Horcajada Sergiu Albu Carlos Casasnovas Anna Rull Laia Reverte Beatriz Dietl David Dalmau Maria J. Arranz Laia Llucià-Carol Anna M. Planas Jordi Pérez-Tur Israel Fernandez-Cadenas Paula Villares Jair Tenorio Roger Colobran Andrea Martin-Nalda Pere Soler-Palacin Francesc Vidal Aurora Pujol Manel Esteller |
author_sort |
Manuel Castro de Moura |
title |
Epigenome-wide association study of COVID-19 severity with respiratory failure |
title_short |
Epigenome-wide association study of COVID-19 severity with respiratory failure |
title_full |
Epigenome-wide association study of COVID-19 severity with respiratory failure |
title_fullStr |
Epigenome-wide association study of COVID-19 severity with respiratory failure |
title_full_unstemmed |
Epigenome-wide association study of COVID-19 severity with respiratory failure |
title_sort |
epigenome-wide association study of covid-19 severity with respiratory failure |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-04-01 |
description |
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. |
topic |
Coronavirus SARS-CoV-2 COVID-19 Epigenetics DNA methylation |
url |
http://www.sciencedirect.com/science/article/pii/S2352396421001328 |
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doaj-b46e8f4e01864856b49fc6a4d33afe0f2021-04-30T07:22:56ZengElsevierEBioMedicine2352-39642021-04-0166103339Epigenome-wide association study of COVID-19 severity with respiratory failureManuel Castro de Moura0Veronica Davalos1Laura Planas-Serra2Damiana Alvarez-Errico3Carles Arribas4Montserrat Ruiz5Sergio Aguilera-Albesa6Jesús Troya7Juan Valencia-Ramos8Valentina Vélez-Santamaria9Agustí Rodríguez-Palmero10Judit Villar-Garcia11Juan P. Horcajada12Sergiu Albu13Carlos Casasnovas14Anna Rull15Laia Reverte16Beatriz Dietl17David Dalmau18Maria J. Arranz19Laia Llucià-Carol20Anna M. Planas21Jordi Pérez-Tur22Israel Fernandez-Cadenas23Paula Villares24Jair Tenorio25Roger Colobran26Andrea Martin-Nalda27Pere Soler-Palacin28Francesc Vidal29Aurora Pujol30Manel Esteller31Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, SpainJosep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, SpainJosep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, SpainJosep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, SpainNavarra Health Service Hospital, Pamplona, SpainInfanta Leonor University Hospital, Madrid, SpainUniversity Hospital of Burgos, Burgos, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Catalonia, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; University Hospital Germans Trias i Pujol, Badalona, Barcelona, Catalonia, SpainHospital del Mar - IMIM Biomedical Research Institute, Barcelona, Catalonia, SpainHospital del Mar - IMIM Biomedical Research Institute, Barcelona, Catalonia, SpainInstitut Guttmann Foundation, Badalona, Barcelona, Catalonia, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Catalonia, SpainHospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Catalonia, SpainHospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Catalonia, SpainServei de malalties infeccioses Hospital Universitari MutuaTerrassa, Universitat de Barcelona, Barcelona, Catalonia, SpainMutuaTerrassa Research and Innovation Foundation, HIV/AIDS Unit Hospital Universitari MutuaTerrassa, University of Barcelona, Barcelona, Catalonia, SpainFundaciò Docència i Recerca Mutua Terrassa i Hospital Universitari Mutua Terrassa, Barcelona, Catalonia, SpainStroke Pharmacogenomics and Genetics Group, Sant Pau Institute of Research, Sant Pau Hospital, Barcelona, Catalonia, SpainDepartment of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Area of Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, SpainInstitut de Biomedicina de València-CSIC, CIBERNED, Unitat Mixta de Neurologia i Genètica, IIS La Fe, Vallencia, SpainStroke Pharmacogenomics and Genetics Group, Sant Pau Institute of Research, Sant Pau Hospital, Barcelona, Catalonia, SpainInternal Medicine Department, Hospital HM Sanchinarro, HM Hospitales, Madrid, SpainINGEMM-Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain; Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, SpainImmunology Division, Genetics Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Vall d'Hebron Barcelona Hospital Campus, UAB, Barcelona, Catalonia, SpainPediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, SpainPediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, SpainHospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Catalonia, SpainNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain; Corresponding authors.Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Cancer (CIBERONC), Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Catalonia, Spain; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2352396421001328CoronavirusSARS-CoV-2COVID-19EpigeneticsDNA methylation |