Jothi, Swathi, Insel, Michael, Claessen, Guido et al. · Physiological reports · 2025 · DOI
This study compared how bodies use oxygen during exercise in people with long COVID, ME/CFS, and healthy controls. Researchers found that both long COVID and ME/CFS patients had trouble getting oxygen into their muscles during exercise, which was the main reason they couldn't exercise as much as healthy people. If this muscle oxygen problem could be fixed, it might significantly improve exercise ability in both conditions.
This study identifies a shared physiologic mechanism between long COVID and ME/CFS that could explain exercise intolerance in both populations. By pinpointing skeletal muscle oxygen diffusion as a key problem, it opens potential therapeutic targets for improving exercise capacity. Understanding this mechanism is crucial for developing evidence-based treatments rather than relying on symptom management alone.
This study does not prove that fixing skeletal muscle oxygen diffusion will actually improve symptoms in patients—only that the mathematical model suggests potential benefit. The small sample size means findings may not apply to all ME/CFS or long COVID patients. The study identifies correlation between impaired oxygen diffusion and exercise limitation but cannot definitively establish causation or rule out other contributing mechanisms.
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
Jothi, Swathi, Insel, Michael, Claessen, Guido, Kubba, Saad, Howden, Erin J, Ruiz-Carmona, Sergio, et al. (2025). Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.. Physiological reports. https://doi.org/10.14814/phy2.70535
BibTeX
@article{mecfsatlas-jothi-2025-long-covid,
author = {Jothi, Swathi and Insel, Michael and Claessen, Guido and Kubba, Saad and Howden, Erin J and Ruiz-Carmona, Sergio and Levine, Todd and Rischard, Franz P},
title = {Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.},
journal = {Physiological reports},
year = {2025},
doi = {10.14814/phy2.70535},
note = {PubMed: 40892700},
url = {https://www.mecfsatlas.com/evidence/jothi-2025-long-covid},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/jothi-2025-long-covid
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