Many people with ME/CFS or post-COVID are still told that their symptoms are mainly caused by reduced physical activity and the resulting loss of fitness. This new NMCB study shows that this explanation is too simplistic.
Led by Dr Rob Wüst, movement scientist at Vrije Universiteit Amsterdam and researcher within the Dutch ME/CFS Cohort and Biobank (NMCB), researchers compared the muscles of people with ME/CFS and post-COVID with those of healthy individuals who had undergone 60 days of complete bed rest. The findings were recently published in the scientific journal Nature Communications. (Charlton, B.T., Slaghekke, A., Appelman, B. et al. Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest. Nat Commun (2026). https://doi.org/10.1038/s41467-026-75725-y)
Why is this study important?
Many people with ME/CFS and post-COVID have a severely reduced exercise capacity. Many patients also experience post-exertional malaise (PEM), meaning that their symptoms worsen following physical, cognitive, or emotional exertion.
Because people with ME/CFS and post-COVID often reduce their activity levels to avoid worsening their symptoms, it is sometimes assumed that their symptoms are primarily the result of deconditioning.
To investigate whether this assumption is correct, the researchers compared people with ME/CFS and post-COVID with healthy individuals who had remained on complete bed rest for 60 days. If prolonged physical inactivity were the main cause of the observed abnormalities, the muscles of both groups would be expected to look very similar.
This was not the case.
How was the study conducted?
The researchers compared four groups:
- Healthy individuals who completed 60 days of strict bed rest;
- People with post-COVID;
- People with ME/CFS;
- Healthy control participants matched for age and sex.
All participants performed a maximal exercise test. Participants in the bed rest group completed this test both before and after the 60-day bed rest period.
In addition, the researchers collected small muscle biopsies to examine muscle fibres, the small blood vessels (capillaries), and the mitochondria—the energy-producing structures within cells.
What did the researchers discover?
People with ME/CFS, people with post-COVID, and healthy participants after 60 days of bed rest all showed a lower exercise capacity than healthy controls. However, the muscles of patients differed clearly from those of healthy individuals following prolonged bed rest.
- No general muscle wasting
Healthy participants lost a substantial amount of muscle mass after 60 days of bed rest.
In contrast, researchers did not observe this general muscle wasting in people with ME/CFS or post-COVID.
If prolonged inactivity were the sole cause of patients’ symptoms, their muscles would be expected to resemble those of healthy individuals after prolonged bed rest. The study showed that this is not the case.
- Different muscle fibre composition
The researchers also identified differences in muscle fibre composition.
People with ME/CFS and post-COVID had fewer type I muscle fibres, which are essential for endurance activities, and a relatively higher proportion of type II muscle fibres, which fatigue more quickly.
In people with ME/CFS, the type I muscle fibres were also smaller than normal. This change was not observed in healthy participants after prolonged bed rest.
- Abnormalities in energy production
The researchers also found evidence that the mitochondria—the energy-producing structures within cells—function less efficiently in people with ME/CFS and post-COVID.
According to the researchers, these abnormalities cannot be explained by reduced physical activity alone. Other biological mechanisms are likely to contribute.
- Fewer capillaries in ME/CFS
People with ME/CFS also had fewer small blood vessels (capillaries) surrounding their muscle fibres. As a result, less oxygen may be delivered to the muscles during physical activity.
This abnormality was not found in healthy participants after prolonged bed rest.
What do these findings mean for patients and future research?
According to the researchers, these findings demonstrate that people with ME/CFS and post-COVID should not simply be regarded as individuals who have lost physical fitness due to inactivity.
This has important implications for the development of future treatments and rehabilitation programmes, which should be based on the biological changes occurring in patients’ muscles rather than on the assumption that deconditioning is the primary problem.
At the same time, this study does not answer all remaining questions. It is still unclear what causes the observed muscle abnormalities and whether they are a cause of the disease or a consequence of it.
The study also mainly included people with relatively mild symptoms, as participants had to visit the research centre several times and complete a maximal exercise test. Therefore, the findings cannot automatically be generalised to people with severe ME/CFS or post-COVID who are housebound or bedbound.
Future research will investigate how these muscle abnormalities contribute to symptoms such as post-exertional malaise (PEM) and how this knowledge can be translated into improved diagnostics and more effective treatments.