Study Reveals Histopathologic Findings in the Muscle and Nerve in Patients With Severe COVID-19

Abnormal inflammatory cell infiltrates and myxovirus resistance protein A (MxA) expression in endothelial cells in muscle and nerve, necrosis of muscle fibers, and abnormal major histocompatibility complex-1 (MHC-1) expression, are common in patients with COVID-19, according to study findings published in Neurology.

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

The objective of the current study was to assess the histopathologic findings in the skeletal muscle and peripheral nerve from autopsies of patients with COVID-19.

Slides were reviewed independently by a neuropathologist and a neurologist board-certified in neuromuscular medicine and clinical neuromuscular pathology. Samples of psoas muscle and femoral nerve were also collected for each patient.

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

Evidence of type 2 fiber atrophy was seen on microscopic examination in 32 of 35 patients with COVID-19, necrotizing myopathy was reported in 9 patients, and myositis in 7 patients who died from COVID-19. Diffuse or multifocal MHC-1 immunostaining of nonnecrotic/nonregenerating muscle fibers was evident in all 16 patients with myositis or necrotizing myopathy and in 8 additional 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 for 1 with evidence of MxA in both myocytes and capillaries. Expression of MxA was also reported in 7 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. Expression of MxA was observed on capillaries in 2 patients from the control group with no evidence of abnormal MxA expression on nerve biopsies.

These findings indicated that in patients with COVID-19, there may be evidence for inflammatory cells infiltrates and MxA expression in endothelial cells in both muscle and nerve, as well as necrosis of muscle fibers, and abnormal MHC-1 expression in muscle.

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

“Although we did not measure cytokine levels in blood, the histopathologic abnormalities seen in our patients suggest that these findings may be secondary to the storm of cytokine release rather than direct viral infection of these tissues,” the researchers wrote.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

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