E0 ConsensusPreliminaryPEM unclearSystematic-ReviewPeer-reviewedReviewed
Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.
Shekhar Patil, Madhura, Richter, Emma, Fanning, Lara et al. · Expert reviews in molecular medicine · 2024 · DOI
Quick Summary
This review examined research on how long-COVID changes the way genes are turned on and off in the body—a process called epigenetics. Researchers found that these changes may affect the immune system, nervous system, and how cells use energy. While the findings are interesting and promise better treatments in the future, current research is still limited in size and quality.
Why It Matters
Understanding epigenetic changes in post-viral conditions like long-COVID may illuminate shared mechanisms with ME/CFS, potentially leading to biomarker-driven subgrouping and targeted therapies for both conditions. This research bridges molecular mechanisms with clinical heterogeneity, offering hope for personalized treatment approaches in prolonged post-infectious illnesses.
Observed Findings
- Six studies identified DNA methylation changes in patients with PACS/long-COVID
- Epigenetic alterations involved immune system, autonomic nervous system, and cellular metabolism pathways
- Two studies examined miRNA expression specifically in long-COVID patients with lung complications
- Most included studies had small sample sizes and poor characterization of patient populations
- No homogeneous synthesis was possible due to heterogeneity in study design and patient definitions
Inferred Conclusions
- Epigenetic mechanisms—particularly DNA methylation—may help explain the heterogeneity and underlying pathophysiology of long-COVID and potentially ME/CFS
- Epigenetic profiling could support patient subgrouping and identification of tailored treatment strategies
- Preliminary evidence is promising but scarce and requires higher-quality, longitudinal studies with well-characterized cohorts
Remaining Questions
- Do epigenetic changes represent causal mechanisms or secondary consequences of long-COVID pathology?
- Can epigenetic signatures reliably distinguish long-COVID patient subgroups and predict treatment response?
What This Study Does Not Prove
This review does not establish causation—epigenetic changes may be consequences rather than drivers of long-COVID symptoms. The small sample sizes and heterogeneous patient populations mean findings cannot yet be generalized to broader patient groups. The review provides evidence mapping rather than definitive proof of specific mechanisms.
Tags
Symptom:Fatigue
Biomarker:Gene ExpressionBlood Biomarker
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:Weak Case DefinitionSmall SampleExploratory OnlyMixed Cohort
Metadata
- DOI
- 10.1017/erm.2024.32
- PMID
- 39435694
- Review status
- Editor reviewed
- Evidence level
- Established evidence from major reviews, guidelines, or evidence maps
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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