Identifying DNA Methylation Patterns in Post COVID-19 Condition: Insights from a One-Year Prospective Cohort Study
Abstract
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 non-hospitalized 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.
https://www.medrxiv.org/content/10.1101/2025.02.28.25323075v1.full
Abstract
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 non-hospitalized 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.
https://www.medrxiv.org/content/10.1101/2025.02.28.25323075v1.full
