tetano
Editor, Senior Moderator
EBioMedicine
. 2021 Apr 14;103339.
doi: 10.1016/j.ebiom.2021.103339. Online ahead of print.
Epigenome-wide association study of COVID-19 severity with respiratory failure
Manuel Castro de Moura[SUP] 1 [/SUP], Veronica Davalos[SUP] 1 [/SUP], Laura Planas-Serra[SUP] 2 [/SUP], Damiana Alvarez-Errico[SUP] 1 [/SUP], Carles Arribas[SUP] 1 [/SUP], Montserrat Ruiz[SUP] 2 [/SUP], Sergio Aguilera-Albesa[SUP] 3 [/SUP], Jes?s Troya[SUP] 4 [/SUP], Juan Valencia-Ramos[SUP] 5 [/SUP], Valentina V?lez-Santamaria[SUP] 6 [/SUP], Agust? Rodr?guez-Palmero[SUP] 7 [/SUP], Judit Villar-Garcia[SUP] 8 [/SUP], Juan P Horcajada[SUP] 8 [/SUP], Sergiu Albu[SUP] 9 [/SUP], Carlos Casasnovas[SUP] 6 [/SUP], Anna Rull[SUP] 10 [/SUP], Laia Reverte[SUP] 10 [/SUP], Beatriz Dietl[SUP] 11 [/SUP], David Dalmau[SUP] 12 [/SUP], Maria J Arranz[SUP] 13 [/SUP], Laia Lluci?-Carol[SUP] 14 [/SUP], Anna M Planas[SUP] 15 [/SUP], Jordi P?rez-Tur[SUP] 16 [/SUP], Israel Fernandez-Cadenas[SUP] 14 [/SUP], Paula Villares[SUP] 17 [/SUP], Jair Tenorio[SUP] 18 [/SUP], Roger Colobran[SUP] 19 [/SUP], Andrea Martin-Nalda[SUP] 20 [/SUP], Pere Soler-Palacin[SUP] 20 [/SUP], Francesc Vidal[SUP] 10 [/SUP], Aurora Pujol[SUP] 21 [/SUP], Manel Esteller[SUP] 22 [/SUP]
Affiliations
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.
Keywords: COVID-19; Coronavirus; DNA methylation; Epigenetics; SARS-CoV-2.
. 2021 Apr 14;103339.
doi: 10.1016/j.ebiom.2021.103339. Online ahead of print.
Epigenome-wide association study of COVID-19 severity with respiratory failure
Manuel Castro de Moura[SUP] 1 [/SUP], Veronica Davalos[SUP] 1 [/SUP], Laura Planas-Serra[SUP] 2 [/SUP], Damiana Alvarez-Errico[SUP] 1 [/SUP], Carles Arribas[SUP] 1 [/SUP], Montserrat Ruiz[SUP] 2 [/SUP], Sergio Aguilera-Albesa[SUP] 3 [/SUP], Jes?s Troya[SUP] 4 [/SUP], Juan Valencia-Ramos[SUP] 5 [/SUP], Valentina V?lez-Santamaria[SUP] 6 [/SUP], Agust? Rodr?guez-Palmero[SUP] 7 [/SUP], Judit Villar-Garcia[SUP] 8 [/SUP], Juan P Horcajada[SUP] 8 [/SUP], Sergiu Albu[SUP] 9 [/SUP], Carlos Casasnovas[SUP] 6 [/SUP], Anna Rull[SUP] 10 [/SUP], Laia Reverte[SUP] 10 [/SUP], Beatriz Dietl[SUP] 11 [/SUP], David Dalmau[SUP] 12 [/SUP], Maria J Arranz[SUP] 13 [/SUP], Laia Lluci?-Carol[SUP] 14 [/SUP], Anna M Planas[SUP] 15 [/SUP], Jordi P?rez-Tur[SUP] 16 [/SUP], Israel Fernandez-Cadenas[SUP] 14 [/SUP], Paula Villares[SUP] 17 [/SUP], Jair Tenorio[SUP] 18 [/SUP], Roger Colobran[SUP] 19 [/SUP], Andrea Martin-Nalda[SUP] 20 [/SUP], Pere Soler-Palacin[SUP] 20 [/SUP], Francesc Vidal[SUP] 10 [/SUP], Aurora Pujol[SUP] 21 [/SUP], Manel Esteller[SUP] 22 [/SUP]
Affiliations
- PMID: 33867313
- DOI: 10.1016/j.ebiom.2021.103339
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.
Keywords: COVID-19; Coronavirus; DNA methylation; Epigenetics; SARS-CoV-2.