Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

• Published in: Acta neuropathologica communications Vol. 11; no. 1; pp. 193 - 20
• Main Authors: Aschman, Tom, Wyler, Emanuel, Baum, Oliver, Hentschel, Andreas, Rust, Rebekka, Legler, Franziska, Preusse, Corinna, Meyer-Arndt, Lil, Büttnerova, Ivana, Förster, Alexandra, Cengiz, Derya, Alves, Luiz Gustavo Teixeira, Schneider, Julia, Kedor, Claudia, Bellmann-Strobl, Judith, Sanchin, Aminaa, Goebel, Hans-Hilmar, Landthaler, Markus, Corman, Victor, Roos, Andreas, Heppner, Frank L, Radbruch, Helena, Paul, Friedemann, Scheibenbogen, Carmen, Dengler, Nora F, Stenzel, Werner
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.12.2023; BioMed Central; BMC
• Subjects: Analysis; Antibodies; Atrophy; Basement membrane thickening; Biopsy; Capillaries; Chronic fatigue syndrome; COVID-19; Exercise; Fatigue; Health aspects; Humans; Infection; Infections; Kinases; Macrophages; Microangiopathy; Muscle, Skeletal; Muscles; Musculoskeletal system; Patients; Post-acute sequelae of COVID-19 (PASC); Post-COVID syndrome; Post-infectious syndrome; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Virus diseases; Germany; SARS-CoV-2; Microangiopathy; Post-COVID syndrome; Post-infectious syndrome; Post-acute sequelae of COVID-19 (PASC); Basement membrane thickening; ME/CFS
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-023-01662-2

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as "long COVID". Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169 macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.