Articles producció científica> Medicina i Cirurgia

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

  • Identification data

    Identifier: imarina:9216710
    Authors:
    Castro de Moura, ManuelDavalos, VeronicaPlanas-Serra, LauraAlvarez-Errico, DamianaArribas, CarlesRuiz, MontserratAguilera-Albesa, SergioTroya, JesusValencia-Ramos, JuanVelez-Santamaria, ValentinaRodriguez-Palmero, AgustiVillar-Garcia, JuditHorcajada, Juan P.Albu, SergiuCasasnovas, CarlosRull, AnnaReverte, LaiaDietl, BeatrizDalmau, DavidArranz, Maria J.Llucia-Carol, LaiaPlanas, Anna M.Perez-Tur, JordiFernandez-Cadenas, IsraelVillares, PaulaTenorio, JairColobran, RogerMartin-Nalda, AndreaSoler-Palacin, PereVidal, FrancescPujol, AuroraEsteller, Manel
    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 stra
  • Others:

    Author, as appears in the article.: Castro de Moura, Manuel; Davalos, Veronica; Planas-Serra, Laura; Alvarez-Errico, Damiana; Arribas, Carles; Ruiz, Montserrat; Aguilera-Albesa, Sergio; Troya, Jesus; Valencia-Ramos, Juan; Velez-Santamaria, Valentina; Rodriguez-Palmero, Agusti; Villar-Garcia, Judit; Horcajada, Juan P.; Albu, Sergiu; Casasnovas, Carlos; Rull, Anna; Reverte, Laia; Dietl, Beatriz; Dalmau, David; Arranz, Maria J.; Llucia-Carol, Laia; Planas, Anna M.; Perez-Tur, Jordi; Fernandez-Cadenas, Israel; Villares, Paula; Tenorio, Jair; Colobran, Roger; Martin-Nalda, Andrea; Soler-Palacin, Pere; Vidal, Francesc; Pujol, Aurora; Esteller, Manel;
    Department: Medicina i Cirurgia
    URV's Author/s: RULL AIXA, ANNA / Vidal Marsal, Francisco
    Keywords: Young adult Virus infection Virology Validation study Spain Severity of illness index Severe acute respiratory syndrome coronavirus 2 Sars-cov-2 Respiratory insufficiency Respiratory failure Reproducibility of results Reproducibility Pyrosequencing Pneumonia Oxygen therapy Noninvasive ventilation Middle aged Mgmt Metabolism Melanoma Male Major histocompatibility antigen class 1 Major clinical study Interferons Interferon Intensive care unit Inflammasome Humans Human Hospitalization Heredity Genome-wide association study Genetics Female Extracorporeal oxygenation Etiology Epigenome Epigenetics Dna methylation Disease severity Cross validation Cpg islands Cpg island Covid-19 Coronavirus disease 2019 Coronavirus Cohort studies Cohort analysis Clinical outcome Chromosome Blood sampling Biological marker Bioinformatics Assisted ventilation Artificial ventilation Article Adult
    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.
    Thematic Areas: Saúde coletiva Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina iii Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Ciências biológicas ii Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all)
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2352-3964
    Author's mail: francesc.vidal@urv.cat
    Author identifier: 0000-0002-6692-6186
    Record's date: 2024-07-27
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.thelancet.com/journals/ebiom/article/PIIS2352-39642100132-8/fulltext
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Ebiomedicine. 66 (103339):
    APA: Castro de Moura, Manuel; Davalos, Veronica; Planas-Serra, Laura; Alvarez-Errico, Damiana; Arribas, Carles; Ruiz, Montserrat; Aguilera-Albesa, Sergio; (2021). Epigenome-wide association study of COVID-19 severity with respiratory failure. Ebiomedicine, 66(103339), -. DOI: 10.1016/j.ebiom.2021.103339
    Article's DOI: 10.1016/j.ebiom.2021.103339
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry, Genetics and Molecular Biology (Miscellaneous),Medicine (Miscellaneous),Medicine, Research & Experimental
    Young adult
    Virus infection
    Virology
    Validation study
    Spain
    Severity of illness index
    Severe acute respiratory syndrome coronavirus 2
    Sars-cov-2
    Respiratory insufficiency
    Respiratory failure
    Reproducibility of results
    Reproducibility
    Pyrosequencing
    Pneumonia
    Oxygen therapy
    Noninvasive ventilation
    Middle aged
    Mgmt
    Metabolism
    Melanoma
    Male
    Major histocompatibility antigen class 1
    Major clinical study
    Interferons
    Interferon
    Intensive care unit
    Inflammasome
    Humans
    Human
    Hospitalization
    Heredity
    Genome-wide association study
    Genetics
    Female
    Extracorporeal oxygenation
    Etiology
    Epigenome
    Epigenetics
    Dna methylation
    Disease severity
    Cross validation
    Cpg islands
    Cpg island
    Covid-19
    Coronavirus disease 2019
    Coronavirus
    Cohort studies
    Cohort analysis
    Clinical outcome
    Chromosome
    Blood sampling
    Biological marker
    Bioinformatics
    Assisted ventilation
    Artificial ventilation
    Article
    Adult
    Saúde coletiva
    Medicine, research & experimental
    Medicine (miscellaneous)
    Medicine (all)
    Medicina iii
    Medicina ii
    Medicina i
    General medicine
    General biochemistry,genetics and molecular biology
    Ciências biológicas ii
    Biotecnología
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
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