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

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.

Young Adults’ Intentions and Rationales for COVID-19 Vaccination Participation: Evidence from a Student Survey in Ho Chi Minh City, Vietnam

“…To compare the decisions on vaccines of both genders, we assume that those who are willing to pay for vaccines and wait for free vaccines are Group 1, named as getting vaccines, while those who hesitate and reject vaccines belong to Group 0, named as no vaccination. Notably, a comparison of median values of vaccine decisions in both genders using the Mann–Whitney U test showed that there are no differences in the correlation within each gender ( p -value = 0.536) (see the last row of Table 3 ) [ 62 ].…”

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors

“…In addition, SARS-CoV-2 has been found to induce changes in DNA methylation, which affect the expression of immune response inhibitory genes that could, in part, contribute to the unfavorable progression of COVID-19 [ 46 ]. Finally, it is noteworthy that a recently identified signature made of 44 variably methylated CpGs has been predictive of subjects at risk of developing worse symptoms after SARS-CoV-2 infection [ 47 ]. Interestingly, none of these newly identified CpGs overlap with those involved in the DNAmAge prediction used in this [ 20 ] or other studies [ 26 ].…”

“…This information was correlated with TL shortening and the expression of ACE2 mRNA. It is too early to extrapolate whether relevant clinical indications may arise from this and other studies assessing the role of epigenetic changes in the COVID-19 syndrome [ 46 , 47 ]. However, a warning might be raised that sequelae of SARS-CoV-2 infection might rely on persistent epigenomic modifications, possibly underlying the presence of a COVID-19 epigenetic memory.…”

Blood DNA methylation and COVID-19 outcomes

“…A recent report comparing patients with and without sepsis of unspecified origin indicates differential methylation at genes that participate in interferon-gammamediated (IFNγ) signaling, MHCII antigen processing and presentation, immunoglobulin production, and cell adhesion pathways [47]. In a limited study of 6 patients with SARS-CoV-2 infection, 6 DMPs (not DMRs) were observed in genes that encode proteins that participate in granulopoiesis and B-lymphocyte-to-granulocyte trans-differentiation [10]; and a very recent report of a larger cohort identifies 44 CpGs in 39 genes that were differentially methylated, including genes related to interferon response to viral infections [48]. It has also been previously reported that viral infections induce aberrant methylation patterns in host cells [33,49].…”