Compared with patients who die without COVID-19 infection, patients who die with severe COVID-19 may present with signs of mild to severe myositis, suggesting that SARS-CoV-2 may be linked to postinfectious, immune-mediated myopathy, according to study results published in JAMA Neurology.
Mild to fatal events of myopathy had been associated with a number of viruses; however, muscle biopsies are not often performed in suspected viral-associated myositis. A team of researchers in Germany conducted a case-control autopsy series as a multidisciplinary postmortem analysis to investigate myocardial and skeletal muscle inflammation in patients with COVID-19 or other critical illnesses who died between March 2020 and February 2021.
The study investigators measured inflammation of skeletal muscle tissue via quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and II antigens on sarcolemma, and conducted a blinded evaluation on a visual analog scale from no detected pathology to significant pathology.
A total of 43 patients with COVID-19 (mean age, 72 years; men, 72%) and 11 patients with critical illnesses other than COVID-19 (mean age, 71 years; men, 64%) were included in the analysis.
Compared with patients with other critical illnesses, skeletal muscle samples from those who had COVID-19 at death had an overall higher pathology score (mean, 1.5 vs 3.4, respectively; P <.001) and a higher inflammation score (mean, 1.0 vs 3.5, respectively; P <.001).
Of the 42 samples from patients with COVID-19, relevant expressions of MHC class I antigens and MHC II antigens on sarcolemma were present in 55% and 17% of samples, respectively. Relevant expressions, however, were not found in any of the control samples.
Compared with control samples, the number of natural killer cells was elevated in samples from patients with COVID-19 (mean, 3 vs 8 cells per 10 high-power fields, respectively; P <.001). There were also more inflammatory features in skeletal muscles than in cardiac muscles, and inflammation was highlighted in patients with COVID-19 with chronic courses.
Although SARS-CoV-2 ribonucleic acid was found in some muscle specimens, direct viral infection of myofibers was not evident in either immunohistochemistry or electron microscopy analyses.
“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,” the study researchers noted.
“Whether these findings can be extrapolated to milder disease courses and potentially explain chronic muscle fatigue syndromes as described in postacute COVID-19 syndromes and whether autoimmune mechanisms are involved will need to be addressed in future studies,” the authors concluded.
Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Aschman T, Schneider J, Greuel S, et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurol. Published online June 11, 2021. doi:10.1001/jamaneurol.2021.2004