Skeletal Muscle in PASC and ME/CFS Patients

Rationale: A common feature in patients with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are skeletal muscle-related symptoms, such as muscle pain, weakness, fatigue and post-exertional malaise. Objective: The primary aim is to determine markers for skeletal muscle structure and function, and circulating factors, in patients with PASC and ME/CFS, and compare with controls. The secondary objective is to determine skeletal muscle structure and function before and after induction of post-exertional malaise, and assess the relationships between the measures obtained from muscle biopsies and parameters of exercise tolerance. Study design: Case-control observational study Study population: Patients with PASC, ME/CFS and healthy human volunteers, 18 - 65 yr old. Intervention (if applicable): none Main study parameters/endpoints: Primary outcome parameters are markers for local inflammation, viral infiltration, mitochondrial respiratory function and myokine concentrations in a muscle biopsy and venous blood before and after induction of post-exertional malaise. Heart rate variability and measures of exercise performance will also be determined. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will be asked to perform physical exercise tests, give muscle biopsies (2 samples), and various blood samples. There is some extent of burden and risk associated with harvesting muscle biopsies and blood samples, however this will be mitigated by the fact that these procedures will only be carried out by trained physicians. Moreover, the scientific gain from obtaining intracellular information outweighs these relatively quick procedures with minimal discomfort afterwards. The acute risks of the physical exercise measurements are negligible. The main risk for patients is that these patients often suffer from post-exertional malaise, which cause