Study reveals histopathological findings in muscles and nerves in patients with severe COVID-19

Abnormal inflammatory cell infiltrates and the expression of myxovirus resistance protein A (MxA) in endothelial cells in muscles and nerves, necrosis of muscle fibers, and abnormal expression of the Major Histocompatibility Complex-1 (MHC-1) are common findings published in Neurology in patients with COVID-19 to study.

Previous research has indicated high rates of myalgia and fatigue in patients with COVID-19. There have also been reports of myositis, rhabdomyolysis, and Guillain-Barré syndrome and variants.

The aim of the current study was to evaluate the histopathological findings of the skeletal muscles and the peripheral nerve from autopsies of patients with COVID-19.

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The slides were independently reviewed by a neuropathologist and a panel of neurologists certified in neuromuscular medicine and clinical neuromuscular pathology. Samples of the psoas muscle and femoral nerve were also obtained from each patient.

The study sample included 35 consecutive autopsies of patients with COVID-19 (mean age 67.8 years; 34.2% women) who died between April and June 2020. The study also included data from 10 patients who tested negative for COVID-19 (control group; mean age at death 71.3 years; 60% women).

Microscopic examination revealed evidence of type 2 fiber atrophy in 32 of 35 COVID-19 patients, necrotizing myopathy in 9 patients, and myositis in 7 patients who died from COVID-19. Diffuse or multifocal MHC-1 immunostaining of non-necrotic / non-regenerative muscle fibers was evident in all 16 patients with myositis or necrotizing myopathy and in 8 other patients.

Abnormal MxA expression was observed in endothelial cells in 9 of 35 muscle biopsies, including 4 of 9 patients with necrotizing myopathy, 3 of 7 patients with myositis and 2 patients without necrotizing myopathy or myositis. Abnormal MxA was observed only in the capillaries in all patients except 1 with evidence of MxA in both myocytes and capillaries. The expression of MxA was also reported in 7 out of 35 nerve biopsies.

Neuritis was observed on microscopic examination of the nerve in 9 patients, including 4 patients with evidence of myositis.

In the control group, muscle biopsies showed type 2 atrophy in all patients and necrotic muscle fibers in 1 patient. However, there was no evidence of myositis. MxA expression in capillaries was observed in 2 patients in the control group, with no evidence of abnormal MxA expression in nerve biopsies.

These results indicated that there may be evidence of inflammatory cell infiltration and MxA expression in endothelial cells in both muscles and nerves, as well as necrosis of muscle fibers and abnormal MHC-1 expression in muscle in patients with COVID-19.

The study had several limitations, including a selection bias in patients with the most severe infections who ultimately died from SARS-CoV-2 infection, and examining the psoas muscle and femoral nerve with no information as to whether they were clinically involved.

“Although we did not measure cytokine levels in the blood, the histopathological abnormalities observed in our patients suggest that these results are due to the storm of cytokine release rather than direct viral infection of these tissues,” the researchers write.

Disclosure: A study author stated links with biotech, pharmaceutical, and / or device companies. For a full list of specifications, see the original reference.


J. Suh, SS Mukerji, SI Collens, et al. Skeletal muscle and peripheral nerve histopathology in COVID-19. Neurology. Published online August 24, 2021. doi: 10.1212 / WNL.0000000000012344.

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