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Compared with patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, skeletal muscle characteristics differ between patients and healthy individuals after bed rest, physical inactivity cannot solely explain the lower exercise capacity and skeletal muscle adaptations in long COVID and ME/CFS patients.
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Abstract Patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from a reduced exercise capacity, skeletal muscle abnormalities and post-exertional malaise (PEM), where symptoms worsen with cognitive or physical exertion. PEM often results in avoidance of physical activity, resulting in a lower aerobic fitness, which may contribute to skeletal muscle abnormalities. Here, we compared whole-body exercise responses and skeletal muscle adaptations after strict 60-day bed rest in healthy people with those in patients with long COVID and ME/CFS, and healthy age- and sex-matched controls. Bed rest altered the respiratory and cardiovascular responses to (sub)maximal exercise, while patients exhibited respiratory alterations only at submaximal exercise. Bed rest caused muscle atrophy, and the reduced oxidative phosphorylation related to reductions in maximal oxygen uptake. Patients with long COVID and ME/CFS did not have muscle atrophy, but had less capillaries and a more glycolytic fibers, none of which were associated with maximal oxygen uptake. While the whole-body aerobic capacity is similar following bed rest compared to patients, the skeletal muscle characteristics differed, suggesting that physical inactivity alone does not explain the lower exercise capacity in long COVID and ME/CFS.
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@article{Charlton2026Skeletal,
title = {Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest},
author = {Braeden T. Charlton and Anouk Slaghekke and Brent Appelman and Moritz Eggelbusch and Jelle Y Huijts and Wendy Noort and Paul W. Hendrickse and Frank W. Bloemers and Jelle J Posthuma and Paul van Amstel and Richie P. Goulding and Hans Degens and Richard T. Jaspers and Michèle van Vugt and Rob C. I. Wüst},
journal = {Nature Communications},
year = {2026},
doi = {10.1038/s41467-026-75725-y},
url = {https://doi.org/10.1038/s41467-026-75725-y}
}
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