Dr. Rob Wüst, physiology professor at the Vrije de Universiteit (Netherlands) and winner of a Solve Ramsay Research Grant, studies how diseases like Long Covid and ME/CFS affect muscle physiology. Recently, he studied how Long Covid– and ME/CFS-related muscle changes relate to deconditioning, the physiological effects of prolonged inactivity.
People sometimes assume that individuals with Long Covid or ME/CFS are weaker because they have become deconditioned and their muscular and cardiovascular systems have atrophied. According to this view, doing more cardiovascular exercises should restore physical conditioning and reduce symptoms.
In this study, Dr. Wüst’s team tested whether deconditioning-associated physiological changes could explain the reduced ability to exercise seen in many people with Long Covid or ME/CFS. The researchers compared muscle physiologies and exercise performance among four groups: healthy people, people with Long Covid, people with ME/CFS, and people with physical inactivity–induced deconditioning. (For the deconditioned group, the team used data from an earlier European Space Agency study on how spaceflight-associated deconditioning may affect astronaut physiologies. Participants in that study underwent deconditioning by remaining on strict bed rest for a full two months!)
As expected, people who underwent inactivity-induced deconditioning performed worse on exercise tests than healthy people. They were weaker and consumed less oxygen during a cycling test. Deconditioning atrophied their muscle fiber muscles, affecting both type I fibers (which contract slowly but resist fatigue) and type II (which contract quickly but fatigue more easily). In these deconditioned participants, poorer exercise performance significantly associated with reduced oxidative phosphorylation by muscle mitochondria. This suggested that for these people, impaired muscle mitochondrial function substantially explained the exercise problems.
People with either Long Covid or ME/CFS performed about as poorly on the exercise tests as those who had undergone deconditioning. But their muscles had changed in different ways. In people with Long Covid or ME/CFS, muscle atrophy primarily affected type I fibers, not type II. And capillaries no longer properly sustained muscle tissues. These changes were especially pronounced in people with ME/CFS. Furthermore, for people with Long Covid or ME/CFS, exercise performance no longer associated with muscle mitochondrial oxidative phosphorylation, suggesting that impaired mitochondrial function alone could not fully explain the exercise problems.
Overall, these results suggest that the physiological changes that make exercise difficult for people with Long Covid or ME/CFS differ from those caused by deconditioning. For people who become deconditioned through physical inactivity, muscle mitochondria dysfunction substantially accounts for poorer physical performance. In contrast, people with Long Covid or ME/CFS appear to be affected by other factors, like atrophied type 1 muscle fibers and poor muscle vascularization.
This work is important because it challenges the common assumption that people with Long Covid or ME/CFS struggle to exercise simply because they are less physically active. Thus, rehabilitation programs designed to reverse deconditioning-induced changes would be inadequate, and maybe even inappropriate, for addressing the muscle changes associated with these diseases. More effective rehabilitation programs may need to account for the unique ways that Long Covid and ME/CFS affect muscles.
Dr. Wüst’s team noted some limitations to the study. First, although Long Covid and ME/CFS may affect muscle tissue differently from deconditioning, people with these illnesses are often less physically active than healthy people and therefore may experience some deconditioning too. More work is needed to understand how the combination of disease and deconditioning affect muscles. Second, these results may not apply to people with severe symptoms of Long Covid or ME/CFS because people with severe symptoms could not easily take part in this study, which involved demanding cycling tests. Finally, some physiological changes were more pronounced for people with ME/CFS than for people with Long Covid, perhaps because the people with ME/CFS had been sick for much longer. Thus, more work is needed to understand the relevant similarities and differences between these conditions.
Dr. Wüst’s team thanked Solve for funding this study, which was published in Nature Communications.
Why This Study Matters:
- Speaks Against a Common Misbelief: Shows how physical inactivity–associated deconditioning cannot fully explain Long Covid– and ME/CFS–associated problems with exercise.
- Lays the Groundwork for Better Treatments: Calls for designing rehabilitation programs that account for unique physiological changes among people with Long Covid or ME/CFS.
- Advances Basic Understanding: Shows how Long Covid and ME/CFS atrophy type I muscle fibers and dysregulate muscle capillaries and mitochondria, thereby informing new ways to diagnose and treat people with these diseases.
Read other study summaries in our Solve Science Spotlight archive here.