Course: Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died
CME Credits: 1.00
Released: 2021-06-11
Key Points
Question Is there a COVID-19–associated myopathy, and is it a viral or postviral phenomenon?Findings In this case-control autopsy study, 26 of 43 individuals (60%) who had died with a diagnosis of COVID-19 showed signs of muscle inflammation, ranging from mild to severe inflammatory myopathy. Inflammation was more pronounced in patients who were chronically ill and those who had seroconverted to SARS-CoV-2 than those who died after acute or subacute courses of COVID-19 and those who died of other illnesses, and no evidence was found for a direct infection of muscle tissue.
Meaning In this study, SARS-CoV-2 was associated with an immune-mediated myopathy.
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.
Educational Objective
To identify the key insights or developments described in this article
View Full Course