Acta Neuropathologica Communications (Dec 2023)
Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles
- Tom Aschman,
- Emanuel Wyler,
- Oliver Baum,
- Andreas Hentschel,
- Rebekka Rust,
- Franziska Legler,
- Corinna Preusse,
- Lil Meyer-Arndt,
- Ivana Büttnerova,
- Alexandra Förster,
- Derya Cengiz,
- Luiz Gustavo Teixeira Alves,
- Julia Schneider,
- Claudia Kedor,
- Judith Bellmann-Strobl,
- Aminaa Sanchin,
- Hans-Hilmar Goebel,
- Markus Landthaler,
- Victor Corman,
- Andreas Roos,
- Frank L. Heppner,
- Helena Radbruch,
- Friedemann Paul,
- Carmen Scheibenbogen,
- Nora F. Dengler,
- Werner Stenzel
Affiliations
- Tom Aschman
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Emanuel Wyler
- Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology
- Oliver Baum
- Institute of Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Andreas Hentschel
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V
- Rebekka Rust
- Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Franziska Legler
- Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Corinna Preusse
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Lil Meyer-Arndt
- Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Ivana Büttnerova
- Department of Autoimmune Diagnostics, Labor Berlin-Charité Vivantes GmbH
- Alexandra Förster
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Derya Cengiz
- Department of Neurology, Medical Faculty, Heinrich-Heine-University
- Luiz Gustavo Teixeira Alves
- Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology
- Julia Schneider
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Claudia Kedor
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Judith Bellmann-Strobl
- Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Aminaa Sanchin
- Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Hans-Hilmar Goebel
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Markus Landthaler
- Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology
- Victor Corman
- Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Andreas Roos
- Department of Pediatric Neurology, Faculty of Medicine, University Children’s Hospital, University of Duisburg-Essen
- Frank L. Heppner
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Helena Radbruch
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Friedemann Paul
- Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Carmen Scheibenbogen
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Nora F. Dengler
- Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- Werner Stenzel
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health
- DOI
- https://doi.org/10.1186/s40478-023-01662-2
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 20
Abstract
Abstract 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. Graphical Abstract
Keywords
- SARS-CoV-2
- Post-COVID syndrome
- Post-acute sequelae of COVID-19 (PASC)
- Post-infectious syndrome
- Microangiopathy
- Basement membrane thickening
