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
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.