Identifying DNA Methylation Patterns in Post COVID-19 Condition: Insights from a One-Year Prospective Cohort Study
Christoffer Granvik, Jelena Smiljanic, Alicia Lind, David Martinez-Enguita, Shumaila Sayyab, Clas Ahlm, Mattias N E Forsell, Sara Cajander, Mika Gustafsson, Martin Rosvall, Johan Normark, Maria Lerm
doi:10.1101/2025.02.28.25323075
The mechanisms underlying Post COVID-19 condition (PCC), with its range of long-lasting symptoms, remain unclear. This study investigates DNA methylation patterns over one year in a subset of nonhospitalized COVID-19 patients with persistent symptoms and reduced quality of life, termed PCC+ (Post COVID-19 condition plus). In a cohort of 22 PCC+ individuals and 22 matched COVID-19 convalescents (PCC-), we identified distinct DNA methylation differences between the groups that diminish over time. Methylation changes in the TXNRD1 gene were significantly associated with cognitive symptoms and fatigue, implicating redox imbalance in PCC pathology. Pathway analysis revealed enrichment in PI3K-Akt and AMPK signaling pathways, potentially underlying the observed efficacy of metformin in reducing PCC incidence. While we found no differences in epigenetic age acceleration between the groups, we observed longitudinal changes in the methylation of the RAS and RAP1 signaling pathways. These findings provide crucial insights into PCC+ mechanisms and suggest oxidative stress pathways as promising targets for therapeutic interventions.
Ethical considerations The study was approved by the Swedish Ethical Review Authority (approval number: 2020-01557) and was carried out according to the declaration of Helsinki.
Data Availability Statement The datasets presented in this article are not readily available because ethical approval does not support publication of the entire dataset of the study cohort. Requests to access the datasets should be directed to johan.normark@umu.se.
Funding The study was supported by grants from SciLifeLab, National COVID-19 Research Program (VC-2020-0015), financed by the Knut and Alice Wallenberg Foundation, Swedish Heart-Lung Foundation (20200325, 202100789 and 20220325).
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