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Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died.
Aschman, Tom; Schneider, Julia; Greuel, Selina; Meinhardt, Jenny; Streit, Simon; Goebel, Hans-Hilmar; Büttnerova, Ivana; Elezkurtaj, Sefer; Scheibe, Franziska; Radke, Josefine; Meisel, Christian; Drosten, Christian; Radbruch, Helena; Heppner, Frank L; Corman, Victor Max; Stenzel, Werner.
  • Aschman T; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schneider J; Department of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Greuel S; Department of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Meinhardt J; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Streit S; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Goebel HH; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Büttnerova I; Department of Autoimmune Diagnostics, Labor Berlin-Charité Vivantes GmbH, Berlin, Germany.
  • Elezkurtaj S; Department of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Scheibe F; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Radke J; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Meisel C; Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Drosten C; Department of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Radbruch H; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Heppner FL; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Corman VM; Berlin Institute of Health, Berlin, Germany.
  • Stenzel W; Cluster of Excellence, NeuroCure, Berlin, Germany.
JAMA Neurol ; 78(8): 948-960, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1265359
Semantic information from SemMedBD (by NLM)
1. Myopathy PROCESS_OF Patients
Subject
Myopathy
Predicate
PROCESS_OF
Object
Patients
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. Paresis PROCESS_OF Patients
Subject
Paresis
Predicate
PROCESS_OF
Object
Patients
4. Myocarditis PROCESS_OF Patients
Subject
Myocarditis
Predicate
PROCESS_OF
Object
Patients
5. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
6. Negative Test Result PROCESS_OF Persons
Subject
Negative Test Result
Predicate
PROCESS_OF
Object
Persons
7. Sarcolemma LOCATION_OF Antigens
Subject
Sarcolemma
Predicate
LOCATION_OF
Object
Antigens
8. Sarcolemma LOCATION_OF Histocompatibility Antigens Class I
Subject
Sarcolemma
Predicate
LOCATION_OF
Object
Histocompatibility Antigens Class I
9. Disease PROCESS_OF Patients
Subject
Disease
Predicate
PROCESS_OF
Object
Patients
10. Inflammation PROCESS_OF Patients
Subject
Inflammation
Predicate
PROCESS_OF
Object
Patients
11. COVID-19 PROCESS_OF Persons
Subject
COVID-19
Predicate
PROCESS_OF
Object
Persons
12. Duration AFFECTS Skeletal muscle structure
Subject
Duration
Predicate
AFFECTS
Object
Skeletal muscle structure
13. Cell-Free RNA CAUSES Negative
Subject
Cell-Free RNA
Predicate
CAUSES
Object
Negative
14. Myopathy COEXISTS_WITH 2019 novel coronavirus
Subject
Myopathy
Predicate
COEXISTS_WITH
Object
2019 novel coronavirus
15. Myopathy PROCESS_OF Patients
Subject
Myopathy
Predicate
PROCESS_OF
Object
Patients
16. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
17. Paresis PROCESS_OF Patients
Subject
Paresis
Predicate
PROCESS_OF
Object
Patients
18. Myocarditis PROCESS_OF Patients
Subject
Myocarditis
Predicate
PROCESS_OF
Object
Patients
19. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
20. Negative Test Result PROCESS_OF Persons
Subject
Negative Test Result
Predicate
PROCESS_OF
Object
Persons
21. Sarcolemma LOCATION_OF Antigens
Subject
Sarcolemma
Predicate
LOCATION_OF
Object
Antigens
22. Sarcolemma LOCATION_OF Histocompatibility Antigens Class I
Subject
Sarcolemma
Predicate
LOCATION_OF
Object
Histocompatibility Antigens Class I
23. Disease PROCESS_OF Patients
Subject
Disease
Predicate
PROCESS_OF
Object
Patients
24. Inflammation PROCESS_OF Patients
Subject
Inflammation
Predicate
PROCESS_OF
Object
Patients
25. COVID-19 PROCESS_OF Persons
Subject
COVID-19
Predicate
PROCESS_OF
Object
Persons
26. Duration AFFECTS Skeletal muscle structure
Subject
Duration
Predicate
AFFECTS
Object
Skeletal muscle structure
27. Cell-Free RNA CAUSES Negative
Subject
Cell-Free RNA
Predicate
CAUSES
Object
Negative
28. Myopathy COEXISTS_WITH 2019 novel coronavirus
Subject
Myopathy
Predicate
COEXISTS_WITH
Object
2019 novel coronavirus
ABSTRACT
Importance Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19.

Objective:

To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. Design, Setting, and

Participants:

This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19. Main Outcomes and

Measures:

Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates.

Results:

Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy. Conclusions and Relevance In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Muscle, Skeletal / COVID-19 / Myocarditis / Myocardium / Myositis Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Neurol Year: 2021 Document Type: Article Affiliation country: Jamaneurol.2021.2004

Full text: Available Collection: International databases Database: MEDLINE Main subject: Muscle, Skeletal / COVID-19 / Myocarditis / Myocardium / Myositis Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Neurol Year: 2021 Document Type: Article Affiliation country: Jamaneurol.2021.2004