Dr. Rob Wüst is a professor at the Vrije de Universiteit (Amsterdam, Netherlands) who specializes in muscle-tissue metabolism and functioning, especially how diseases like Long Covid and ME/CFS damage muscle tissues. In 2022, Dr. Wüst won a Solve Ramsay Research Grant to study muscle dysregulation and post-exertional malaise in patients with infection-associated chronic conditions. Since then, he has published several papers on this important subject. As part of his Solve-funded research, he has now published a review article, in the journal Trends in Endocrinology and Metabolism, about how changes in the muscles of patients with Long Covid relate to post-exertional malaise (PEM). Follow this link to read his review, “Skeletal muscle adaptations and post-exertional malaise in long COVID.”
Research on Long Covid symptoms often relates to the dysregulated immune system or dysregulated nervous system. But in this paper, Dr. Wüst explained how dysregulated muscle tissues may reduce patients’ ability to exercise and increase their post-exertional malaise. (As an exercise physiologist, Dr. Wüst has long studied how PEM relates to exercise.) Mitochondria of patients with Long Covid can become unusually sized and positioned in patients’ muscle cells, and cellular respiration in these mitochondria may decline. The muscle fibers themselves may atrophy, and their composition may change; for example, the fibers that help prevent fatigue (type 1 fibers, which are dense with mitochondria) may become less abundant. Finally, the walls of blood vessels in patients’ muscles may improperly thicken, improperly constrict and dilate, or become damaged. As a result, these blood vessels may bring in too little oxygen and nutrients and inadequately remove harmful metabolites. Importantly, all these changes worsen when patients with Long Covid experience PEM.
Dr. Wüst also reviewed leading hypotheses for why Long Covid changes muscle tissues. For example, the immune system may improperly target important parts of muscle tissues or blood vessels (e.g., β-adrenergic receptors, which are critical for forming new mitochondria and for regulating blood circulation). Another possibility is central fatigue, a condition in which the central nervous system regulates muscle contractions improperly. A third possibility is that patients with Long Covid have weakened musculature because the patients are more sedentary. However, changes in muscles of patients with Long Covid differ from changes in purely sedentary people; so, whether physical inactivity fully accounts for muscle fatigue and PEM in patients is questionable.
Although Dr. Wüst focused on muscle fatigue and PEM in patients with Long Covid, he emphasized that many of these observations apply to patients with ME/CFS too. PEM is typical for patients with ME/CFS, and this symptom is necessary for ME/CFS diagnosis. Also, in several ways, ME/CFS changes patients’ muscle tissues as does Long Covid.
Dr. Wüst noted that although we still lack FDA-approved medicines to reduce PEM in patients with Long Covid, several clinical trials are evaluating treatments like immunoadsorption, dietary supplements, hyperbaric oxygen therapy, anti-inflammatory drugs, and anti-viral drugs. Understanding at the physiological level how Long Covid changes muscle tissues will be critical for these clinical trials to succeed.