Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Neurology. 2021 Aug 24;97(8):e849-e858. doi: 10.1212/WNL.0000000000012344. Epub 2021 Jun 7.

Abstract

Objective: To explore the spectrum of skeletal muscle and nerve pathology of patients who died after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to assess for direct viral invasion of these tissues.

Methods: Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died after SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review.

Results: In SARS-CoV-2-positive patients, mean age at death was 67.8 years (range 43-96 years), and the duration of symptom onset to death ranged from 1 to 49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74% (mean 959 U/L, range 29-8,413 U/L). Muscle showed type 2 atrophy in 32 patients, necrotizing myopathy in 9, and myositis in 7. Neuritis was seen in 9. Major histocompatibility complex-1 (MHC-1) expression was observed in all cases of necrotizing myopathy and myositis and in 8 additional patients. Abnormal expression of myxovirus resistance protein A (MxA) was present on capillaries in muscle in 9 patients and in nerve in 7 patients. SARS-CoV-2 immunohistochemistry was negative in muscle and nerve in all patients. In the 10 controls, muscle showed type 2 atrophy in all patients, necrotic muscle fibers in 1, MHC-1 expression in nonnecrotic/nonregenerating fibers in 3, MxA expression on capillaries in 2, and inflammatory cells in none, and nerves showed no inflammatory cells or MxA expression.

Conclusions: Muscle and nerve tissue demonstrated inflammatory/immune-mediated damage likely related to release of cytokines. There was no evidence of direct SARS-CoV-2 invasion of these tissues.

Classification of evidence: This study provides Class IV evidence that muscle and nerve biopsies document a variety of pathologic changes in patients dying of coronavirus disease 2019 (COVID-19).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • COVID-19 / immunology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / virology
  • Peripheral Nerves / immunology
  • Peripheral Nerves / pathology*
  • Peripheral Nerves / virology