Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Abstract

Objective:To explore the spectrum of skeletal muscle and nerve pathology of patients who died following SARS-CoV-2 infection and assess for direct viral invasion of these tissues.Methods:Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died following 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 1-49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74% (mean 959 U/L, range 29-8413 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 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. 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 non-necrotic/non-regenerating fibers in 3, MxA expression on capillaries in 2, and inflammatory cells in none, and nerves showed no inflammatory cells or MxA expression.Conclusion: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 pathological changes in patients dying with COVID-19.

May macroglossia in COVID-19 be related not only to angioedema?

“…In addition, we found numerous infiltrating macrophages, a critical component of muscle recovery from nerve injury [ 15 ]. Muscle fibers atrophy, inflammatory cells infiltration and nerve pathologic changes have very recently described in autoptic samples from patients dying of COVID-19, thus supporting our observations [ 16 ]. Neuronal damage has been recognized as a COVID-19 complication [ 17 ] and it has been suggested that the taste dysfunction arises from specific cranial nerve involvement, by direct invasion of the SARS-CoV-2 virus into the olfactory and trigeminal nerve cells, or by a demyelinating reaction in olfactory neurons [ 18 ].…”

Myopathy in acute and long-term COVID-19

“…In a recent study, Agergaard and colleagues showed that in patients with long-term muscular complains or fatigue after mild or moderate SARS-CoV-2 infection, myopathy was a common finding ( Agergaard et al, 2021 ). Their study could not provide definite evidence for a causal link between acute infection and long-term myalgia, fatigue and myopathy but it supports the findings from the two recent autopsy studies ( Aschman et al, 2021 , Suh et al, 2021 ).…”

“…Two recent studies investigated skeletal muscle in autopsy specimens from patients with COVID-19 ( Aschman et al, 2021 , Suh et al, 2021 ). Aschman and colleagues showed signs of muscle inflammation, ranging from mild to severe inflammatory myopathy in 60% of the patients who died with severe COVID-19, and the inflammation was more pronounced in skeletal muscle compared to cardiac muscle.…”

Post-COVID symptoms of potential peripheral nervous and muscular origin

“… 20 This finding is relevant in the light of the results of a recent autopsy study of muscle and nerve samples from 35 patients who died due to COVID-19. 21 The authors report evidence of inflammatory or immune-mediated myopathy in 24 patients (69%), with necrotic fibres, inflammatory infiltrates, and diffuse or multifocal expression of major histocompatibility complex class I (MHC-I) in non-necrotic/non-regenerating fibres. Nine patients (26%), seven of whom showed signs of necrotising myopathy or myositis, presented abnormal MxA immunostaining, mainly in muscle capillaries, suggesting overexpression of type 1 interferon in response to infection.…”

“…Nine patients (26%), seven of whom showed signs of necrotising myopathy or myositis, presented abnormal MxA immunostaining, mainly in muscle capillaries, suggesting overexpression of type 1 interferon in response to infection. 21 Another autopsy study analysed striated muscle tissue from 42 patients who died due to severe COVID-19, with most samples displaying signs of myositis of varying intensity. Twenty-three patients (55%) presented overexpression of MHC-I antigens, and seven (17%) presented MHC-II overexpression; neither of these findings were observed in the autopsies performed in any of the 11 controls.…”