Peppercorn, Katie, Sharma, Sayan, Edgar, Christina D et al. · International journal of molecular sciences · 2025 · DOI
This study examined chemical markers called DNA methylation in blood cells from people with ME/CFS, Long COVID, and healthy individuals. Researchers found that while the overall patterns were similar between ME/CFS and Long COVID patients, there were specific differences in which genes were chemically marked, suggesting these two conditions may have related but distinct biological changes. The findings lay groundwork for understanding what makes these post-viral conditions work at a molecular level.
This is the first direct epigenetic comparison between ME/CFS and Long COVID, two conditions that share >95% of symptoms but may have different underlying mechanisms. Understanding these molecular differences could help explain why patients respond differently to treatments and may guide development of condition-specific therapies. These findings open new avenues for biomarker research in post-viral illnesses.
This study does not establish whether methylation changes cause the symptoms of ME/CFS or Long COVID, nor does it prove the conditions are the same or fundamentally different—it only reveals that some epigenetic patterns differ. The small sample size and cross-sectional design cannot determine whether methylation changes precede symptoms, result from the disease process, or correlate with disease severity. The confounding effect of disease duration (12 years vs. 1 year) makes it unclear whether observed differences reflect disease stage or inherent differences between conditions.
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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