Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles
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...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01662-2 |
| _version_ | 1797397698739961856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tom Aschman |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-09T01:14:56Z |
| format | Article |
| id | doaj.art-b65fc0fea9634e6a9d9eb0b43f7c5637 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-09T01:14:56Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-b65fc0fea9634e6a9d9eb0b43f7c56372023-12-10T12:35:17ZengBMCActa Neuropathologica Communications2051-59602023-12-0111112010.1186/s40478-023-01662-2Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal musclesTom Aschman0Emanuel Wyler1Oliver Baum2Andreas Hentschel3Rebekka Rust4Franziska Legler5Corinna Preusse6Lil Meyer-Arndt7Ivana Büttnerova8Alexandra Förster9Derya Cengiz10Luiz Gustavo Teixeira Alves11Julia Schneider12Claudia Kedor13Judith Bellmann-Strobl14Aminaa Sanchin15Hans-Hilmar Goebel16Markus Landthaler17Victor Corman18Andreas Roos19Frank L. Heppner20Helena Radbruch21Friedemann Paul22Carmen Scheibenbogen23Nora F. Dengler24Werner Stenzel25Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthMax Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems BiologyInstitute of Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthLeibniz-Institut Für Analytische Wissenschaften - ISAS - E.VExperimental 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 HealthExperimental 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 HealthDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthExperimental 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 HealthDepartment of Autoimmune Diagnostics, Labor Berlin-Charité Vivantes GmbHDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Neurology, Medical Faculty, Heinrich-Heine-UniversityMax Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems BiologyInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthInstitute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthExperimental 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 HealthDepartment of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthMax Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems BiologyInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Pediatric Neurology, Faculty of Medicine, University Children’s Hospital, University of Duisburg-EssenDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthExperimental 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 HealthInstitute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of HealthAbstract 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 Abstracthttps://doi.org/10.1186/s40478-023-01662-2SARS-CoV-2Post-COVID syndromePost-acute sequelae of COVID-19 (PASC)Post-infectious syndromeMicroangiopathyBasement membrane thickening |
| spellingShingle | 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 Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles Acta Neuropathologica Communications SARS-CoV-2 Post-COVID syndrome Post-acute sequelae of COVID-19 (PASC) Post-infectious syndrome Microangiopathy Basement membrane thickening |
| title | Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| title_full | Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| title_fullStr | Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| title_full_unstemmed | Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| title_short | Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| title_sort | post covid exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles |
| topic | SARS-CoV-2 Post-COVID syndrome Post-acute sequelae of COVID-19 (PASC) Post-infectious syndrome Microangiopathy Basement membrane thickening |
| url | https://doi.org/10.1186/s40478-023-01662-2 |
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