Thread by @RobWust

After a long wait, our longitudinal long COVID study is finally published in @NatureComms: . We find a skeletal muscle alterations in patients with #longcovid, which worsen with exercise. 1/nnature.com/articles/s4146…

With @BraedenCharlton, and clinical colleagues (Brent Appelman and Michele van Vugt), we confirmed the lower exercise capacity in patients with #longcovid, which can partly be explained by changes in skeletal muscle structure and function 2/n

@BraedenCharlton We next wanted to find out if skeletal muscle abnormalities contribute to the feeling of muscle pain, and fatigue one day after an exercise test on a bike. We found that in some #longcovid patients there was extensive muscle damage, but also signs of repair 3/n

@BraedenCharlton Skeletal muscle mitochondrial function and metabolism were altered in patients with #longcovid, and this worsened after induction of post-exertional malaise (PEM). Intense exercise is not good for patients with long COVID! 4/n

@BraedenCharlton Blocking of capillaries by amyloid-containing deposits (or microclots) could reduced exercise capacity. We found these deposits in muscle tissue, but surprisingly not inside capillaries. They were located in between fibers, were higher in patients, and went up after exercise 5/n

@BraedenCharlton We tested whether viral persistence contribute, and screened muscle biopsies for the N-protein. We saw equal amounts in patients and healthy controls (who recovered after COVID). No viral particles were inside cells, so we assume remnants and not active viral particles 6/n

@BraedenCharlton This study contributed to our understanding of muscle pain, fatigue and weakness in patients, and provides a biological substrate for the disease. It doesn’t directly point to the cause of the disease, but highlights that exercise can worsen symptoms in patients 7/n

@BraedenCharlton To reduce the skeletal muscle abnormalities (reduction in mitochondrial function, muscle damage and more microclots), we can only recommend to avoid strenuous exercise for now. Every patient likely has a different threshold for induction of post-exertional malaise. 8/n

@BraedenCharlton We obviously have NOT sit still in the time that this publication has been reviewed. We hope that in the near future we can contribute more knowledge on how exercise links to the disease, and what can be done to reduce PEM. Stay tuned! 9/9

This collaboration between @amsterdamumc, @VUamsterdam, @VU_FGB, and @AMSmovement would not have been possible without the help of so many students, colleagues, and private funders. We also acknowledge the contribution of @PlzSolveCFS, @patientled, and @ZonMw for future work!2/m

@amsterdamumc @VUamsterdam @VU_FGB @AMSmovement @PlzSolveCFS @patientled @ZonMw Last but not least, we really want to thank all patients who participated, who stepped on that bike knowing that they will feel worse the next days/weeks. All the patient contacts online, via email, in person, everyone helped to put the 🧩 together! Together we make a difference