Shankar, Vishnu, Wilhelmy, Julie, Curtis, Ellis J et al. · Proceedings of the National Academy of Sciences of the United States of America · 2025 · DOI
Researchers found that both ME/CFS and Long COVID patients have higher levels of oxidative stress—a harmful buildup of unstable molecules—in their immune cells, particularly in a type of white blood cell called memory T cells. The study identified specific problems with how the body clears this oxidative stress and showed that the existing medication metformin might help reduce overgrowth of these immune cells. Importantly, they discovered these problems show different patterns in men and women, suggesting that sex-specific treatment approaches may be needed.
This study provides the first molecular evidence that ME/CFS and Long COVID share an underlying oxidative stress mechanism, validating the clinical observation that these conditions are similar. Identifying metformin as a potential treatment with sex-specific efficacy offers a concrete lead for clinical trials and suggests a path toward precision medicine approaches. Understanding these mechanisms could enable development of better diagnostic blood tests and more targeted therapies for both conditions.
This study does not prove that oxidative stress is the primary cause of ME/CFS or Long COVID—it may be secondary to other pathological processes. The findings are from isolated blood cells stimulated in the laboratory, so they may not fully reflect what happens in the patient's living body. The sex-specific differences observed require larger studies to confirm and do not yet establish whether metformin will be effective in actual patients, only that it works in laboratory assays.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Shankar, Vishnu, Wilhelmy, Julie, Curtis, Ellis J, Michael, Basil, Cervantes, Layla, Mallajosyula, Vamsee, et al. (2025). Oxidative stress is a shared characteristic of ME/CFS and Long COVID.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2426564122
BibTeX
@article{mecfsatlas-shankar-2025-oxidative-stress,
author = {Shankar, Vishnu and Wilhelmy, Julie and Curtis, Ellis J and Michael, Basil and Cervantes, Layla and Mallajosyula, Vamsee and Davis, Ronald W and Snyder, Michael and Younis, Shady and Robinson, William H and Shankar, Sadasivan and Mischel, Paul S and Bonilla, Hector and Davis, Mark M},
title = {Oxidative stress is a shared characteristic of ME/CFS and Long COVID.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2025},
doi = {10.1073/pnas.2426564122},
note = {PubMed: 40627396},
url = {https://www.mecfsatlas.com/evidence/shankar-2025-oxidative-stress},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/shankar-2025-oxidative-stress
Contribute
Private, reviewed by a human. Not a public comment thread.