Komaroff, Anthony L, Dantzer, Robert · Cell reports. Medicine · 2025 · DOI
This review examines why long COVID and ME/CFS cause such severe, lasting symptoms. Researchers found that both conditions share similar biological problems, including immune system misbehavior, problems with blood vessel function, and issues with how cells produce energy. The study suggests that symptoms may come from both these biological problems and from ancient survival responses in the brain that were meant to protect us during serious illness.
This comprehensive framework helps explain why ME/CFS symptoms persist for years and suggests specific biological targets for treatment. By identifying shared mechanisms between long COVID and ME/CFS, it could accelerate development of therapies and improve recognition that these are biomedical conditions, not psychological ones. Understanding that ancient protective brain circuits may be causing symptoms opens new therapeutic avenues that could potentially reduce suffering for millions of patients.
This review does not prove that any single mechanism causes all symptoms in all patients—ME/CFS and long COVID are likely heterogeneous conditions with multiple contributing factors. It does not establish causation through new experimental evidence, but rather synthesizes existing findings, and therefore cannot confirm which mechanisms are primary versus secondary. The article also does not demonstrate that targeting neuroinflammation will successfully treat these conditions in clinical practice.
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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Primary citation
Komaroff, Anthony L & Dantzer, Robert (2025). Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.. Cell reports. Medicine. https://doi.org/10.1016/j.xcrm.2025.102259
BibTeX
@article{mecfsatlas-komaroff-2025-causes-symptoms,
author = {Komaroff, Anthony L and Dantzer, Robert},
title = {Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Cell reports. Medicine},
year = {2025},
doi = {10.1016/j.xcrm.2025.102259},
note = {PubMed: 40744021},
url = {https://www.mecfsatlas.com/evidence/komaroff-2025-causes-symptoms},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/komaroff-2025-causes-symptoms
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