Appelman, Brent, Charlton, Braeden T, Goulding, Richie P et al. · Nature communications · 2024 · DOI
This study looked at muscle tissue changes in long COVID patients, particularly focusing on post-exertional malaise (PEM)—the worsening of fatigue and pain after activity. Researchers found that muscles in long COVID patients showed structural damage, metabolic problems, and unusual deposits that got worse after activity triggered PEM. These findings help explain why exertion makes symptoms worse in some long COVID patients.
This research provides biological evidence for post-exertional malaise, a hallmark symptom of ME/CFS and long COVID that many patients experience but has lacked clear mechanistic explanation. Understanding muscle-level pathology could inform future diagnostic tests and targeted treatments. The findings validate patient experiences of symptom worsening after exertion with measurable physiological changes.
This study does not prove that muscle pathology is the sole cause of PEM—other systems (neurological, immune, mitochondrial) may also contribute. The case-control design cannot establish whether the observed muscle changes are a cause or consequence of reduced exercise capacity. The findings are correlational and require validation in larger, prospective studies before clinical application.
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
Appelman, Brent, Charlton, Braeden T, Goulding, Richie P, Kerkhoff, Tom J, Breedveld, Ellen A, Noort, Wendy, et al. (2024). Muscle abnormalities worsen after post-exertional malaise in long COVID.. Nature communications. https://doi.org/10.1038/s41467-023-44432-3
BibTeX
@article{mecfsatlas-appelman-2024-muscle-abnormalities,
author = {Appelman, Brent and Charlton, Braeden T and Goulding, Richie P and Kerkhoff, Tom J and Breedveld, Ellen A and Noort, Wendy and Offringa, Carla and Bloemers, Frank W and van Weeghel, Michel and Schomakers, Bauke V and Coelho, Pedro and Posthuma, Jelle J and Aronica, Eleonora and Joost Wiersinga, W and van Vugt, Michèle and Wüst, Rob C I},
title = {Muscle abnormalities worsen after post-exertional malaise in long COVID.},
journal = {Nature communications},
year = {2024},
doi = {10.1038/s41467-023-44432-3},
note = {PubMed: 38177128},
url = {https://www.mecfsatlas.com/evidence/appelman-2024-muscle-abnormalities},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/appelman-2024-muscle-abnormalities
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