ZusammenfassungThis project aims to investigate whether SARS-CoV-2 infection has a persistent impact on the DNA methylation (DNAm) profile of infected individuals up to 4 months after infection, and to assess whether such epigenetic changes correlate to severity of disease and associated negative outcomes in the general population. DNAm is to be measured using whole blood samples collected up to 4 months after a COVID-19 first positive test from participants from the NAKO study. Due to the study design of the NAKO study, the selected sample should capture varying degrees of disease severity (asymptomatic, mild to moderate cases of COVID-19), as well as exposed individuals who did not acquire the infection (controls). Data from NAKO participants will be jointly analyzed with methylation and clinical data from other participating cohorts in the ORCHESTRA Consortium, where severe cases will be selected from hospital-based cohorts (e.g. NAPKON). This study design and the conduction of epigenome-wide association analyses (EWAS) will allow us to investigate epigenetic DNA methylation signatures associated with varying severity degrees of symptomatic disease in a population-based in comparison to a hospital-based setting. Genomic sites identified to be differentially methylated will be brought forward to follow-up analyses, including pathway and gene ontology enrichment. Cell-deconvolution methods will also be applied in order to investigate associated changes in blood cell composition and identify the cell populations driving the epigenetic signature identified. Whether and how the pervasive changes identified in this study are similar to those changes captured in the recently developed EPICOVID, a DNAm signature of disease severity in COVID-19 patients with no comorbidities, will be also assessed. Epigenetic age acceleration, or the difference between an individual’s chronological age and DNAm-estimated biological age, will also be evaluated and compared across disease severity groups.

Schlüsselwörter COVID-19 DNA-methylation SARS-CoV-2 epigenetics

EinrichtungenHelmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Helmholtz Zentrum München