Haunhorst, Simon, Dudziak, Diana, Scheibenbogen, Carmen et al. · Infection · 2025 · DOI
This review examines why people with ME/CFS and long COVID feel much worse after physical activity—a condition called post-exertional malaise. The researchers found that when these patients exercise, their bodies struggle to use oxygen properly and produce energy efficiently, likely due to problems with tiny blood vessels and lingering immune activation. This causes a buildup of harmful substances like lactate and triggers further inflammation and exhaustion.
Understanding the biological mechanisms behind post-exertional malaise is crucial because it affects most ME/CFS patients profoundly and remains poorly understood. This comprehensive review connects multiple organ systems—circulation, energy production, and immunity—suggesting that PEM is not simply deconditioning or psychological, which validates patient experiences. The findings may guide development of targeted treatments and inform safer activity management strategies for affected patients.
This review does not prove causation or establish which mechanism is primary versus secondary; the relationships described may be bidirectional or interdependent. It does not validate any specific treatment or provide clinical trial evidence for interventions. The review synthesizes existing evidence but does not introduce new experimental data that definitively confirms the proposed mechanistic model in human subjects.
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
Haunhorst, Simon, Dudziak, Diana, Scheibenbogen, Carmen, Seifert, Martina, Sotzny, Franziska, Finke, Carsten, et al. (2025). Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.. Infection. https://doi.org/10.1007/s15010-024-02386-8
BibTeX
@article{mecfsatlas-haunhorst-2025-towards-understanding,
author = {Haunhorst, Simon and Dudziak, Diana and Scheibenbogen, Carmen and Seifert, Martina and Sotzny, Franziska and Finke, Carsten and Behrends, Uta and Aden, Konrad and Schreiber, Stefan and Brockmann, Dirk and Burggraf, Paul and Bloch, Wilhelm and Ellert, Claudia and Ramoji, Anuradha and Popp, Juergen and Reuken, Philipp and Walter, Martin and Stallmach, Andreas and Puta, Christian},
title = {Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Infection},
year = {2025},
doi = {10.1007/s15010-024-02386-8},
note = {PubMed: 39240417},
url = {https://www.mecfsatlas.com/evidence/haunhorst-2025-towards-understanding},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/haunhorst-2025-towards-understanding
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