Epigenetic Regulation in SARS-CoV-2 Infection
Summary
Epigenetic regulation comprises heritable alterations in gene expression without changes to the DNA sequence itself, encompassing DNA methylation, histone modifications and chromatin remodelling. During SARS-CoV-2 infection, the host epigenome is dynamically reprogrammed by both viral and immune stimuli, shaping antiviral defences, inflammatory responses and long-term sequelae. Patterns of DNA methylation at promoters and enhancers of immune genes can be hypo- or hypermethylated in response to infection, influencing cytokine production, interferon signalling and antigen presentation. Histone acetylation and methylation modulate chromatin accessibility to transcription factors, with several epigenetic enzymes emerging as potential therapeutic targets. Persistent epigenetic changes may underlie post-acute sequelae of COVID-19, including dysregulated airway epithelial function and accelerated biological ageing. Understanding these mechanisms offers routes to precision interventions that restore healthy epigenetic landscapes and mitigate long-term complications.
Research from Nature Portfolio
Recent studies have linked accelerated epigenetic ageing in blood to both susceptibility to SARS-CoV-2 infection and severity of COVID-19. Using high-density methylation arrays, investigators applied multiple epigenetic-clock algorithms alongside telomere length estimators to profile over 600 individuals’ methylomes before, during and after infection. They observed that greater age acceleration and telomere attrition correlate with more severe disease, while partial reversal of epigenetic age occurs in some survivors during convalescence. These findings highlight epigenetic age as a dynamic biomarker of viral impact and recovery trajectory, suggesting that interventions modulating the epigenetic clock could influence outcomes and long-term health after infection.
Epigenetic Regulation in SARS-CoV-2 Infection publication trend
The graph below shows the total number of articles in epigenetic regulation in sars-cov-2 infection across all publications each year (not limited to Nature Index journals).
Technical terms
Epigenetic regulation: Heritable changes in gene expression without alteration of DNA sequence.
DNA methylation: Addition of methyl groups to cytosine bases in DNA, often at CpG sites, modulating gene transcription.
Histone modification: Post-translational chemical alterations of histone proteins that affect chromatin structure and gene accessibility.
Chromatin remodelling: ATP-dependent reorganisation of nucleosome positioning, regulating DNA accessibility for transcription factors.
Epigenetic clock: Algorithmic estimation of biological age based on DNA methylation signatures.
Telomere attrition: Progressive shortening of chromosomal end regions with cell division, associated with cellular ageing and stress.
References
- A methylation clock model of mild SARS‐CoV‐2 infection provides insight into immune dysregulation. Molecular Systems Biology (2023).
- DNA methylation changes during acute COVID-19 are associated with long-term transcriptional dysregulation in patients’ airway epithelial cells. EMBO Molecular Medicine (2025).
- HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells. Frontiers in Cellular and Infection Microbiology (2023).
- Accelerated biological aging in COVID-19 patients. Nature Communications (2022).
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