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Neuromuscular complications have been reported in patients with COVID-19, but the effect of SARS-CoV-2 (the virus that causes COVID-19) on nerves and muscles is unclear. To address this question, two research groups examined nerve and muscle biopsies from autopsies of patients with COVID-19.
Aschman and colleagues performed a case–control study in which they obtained quadriceps, deltoid, heart, and lung tissue from 43 patients who died with COVID-19 and 11 patients without COVID-19 who died from critical illness. Compared with controls, COVID-19 patients had significantly more degenerating muscle fibers and inflammation on immunohistochemical analysis and a higher average creatine kinase level. Of the COVID-19 muscle samples, 55% showed upregulation of major histocompatibility complex class 1 (MHC-1) antigens, compared with no control samples. COVID-19 muscle biopsies also had natural killer cells near muscle fibers and myxovirus resistance protein A (MxA) staining in capillaries. Among the COVID-19 samples, RT-PCR detected SARS-CoV-2 in 16% of quadriceps muscle and 5% of deltoid muscle tested; however, antibodies for spike protein and analysis with electron microscopy failed to detect SARS-CoV-2 in these samples.
Suh and colleagues performed a case–control study comparing psoas muscle and femoral nerve histopathology between 35 patients who died after SARS-CoV-2 infection and 10 controls without SARS-CoV-2 infection. Muscle biopsies from infected patients showed more necrosis and inflammation and increased of MHC upregulation compared with control biopsies. Among femoral nerve biopsies from infected patients, 25.7% had inflammation and 20% had MxA staining in capillaries; no control nerves showed these features. Immunohistochemistry for SARS-CoV-2 was negative in all muscle and nerve samples.
Aschman T et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurol 2021 Jun 11; [e-pub]. (https://doi.org/10.1001/jamaneurol.2021.2004)
Suh J et al. Skeletal muscle and peripheral nerve histopathology in COVID-19. Neurology 2021 Jun 7; [e-pub]. (https://doi.org/10.1212/WNL.0000000000012344)
Comment
In people with COVID-19, the presence of neuromuscular conditions such as myositis, rhabdomyolysis, and Guillain-Barré syndrome has led to speculation that direct viral invasion of muscles, nerves, or both may underly neuromuscular complications of COVID-19. However, these two histopathology studies did not show direct viral invasion of muscles or nerves. Inflammation was seen in a portion of COVID-19 muscle and nerve biopsies, which was likely due to circulating cytokines. Muscle inflammation and necrosis are known features of viral myositis, which has been associated with many viruses. Future studies to examine which of these muscle biopsy features are specific to SARS-CoV-2 as opposed to other severe viral infections will be useful.