Blood DNA methylation and COVID-19 outcomes

• Published in: Clinical epigenetics Vol. 13; no. 1; p. 118
• Main Authors: Balnis, Joseph, Madrid, Andy, Hogan, Kirk J, Drake, Lisa A, Chieng, Hau C, Tiwari, Anupama, Vincent, Catherine E, Chopra, Amit, Vincent, Peter A, Robek, Michael D, Singer, Harold A, Alisch, Reid S, Jaitovich, Ariel
• Format: Journal Article
• Language: English
• Published: Germany BioMed Central Ltd 25.05.2021; BioMed Central
• Subjects: Acute respiratory distress syndrome; Age; Aged; Aged, 80 and over; Autoimmune diseases; Cell activation; Comparative analysis; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - mortality; CpG islands; Deoxyribonucleic acid; Disease; DNA; DNA methylation; DNA Methylation - physiology; Epidemics; Epigenetics; Female; Gene expression; Genes; Genetic research; Genomes; Genomics; Health aspects; Humans; Immune response; Infections; Intensive care; Male; Methylation; Middle Aged; Mortality; New York - epidemiology; Ontology; Pandemics; Patients; Prospective Studies; Regression analysis; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Ventilators; Viral infections; Virus diseases; New York; COVID-19; DNA methylation; Gene expression; Acute respiratory distress syndrome (ARDS); Mortality; Outcomes
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-021-01102-9

There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data. Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score. Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.