Neuromuscular Complications of COVID-19: Evidence from the Third Year of the Global Pandemic.

Accumulating evidence in the third year of the global pandemic suggests that coronavirus disease 2019 (COVID-19) can cause neuromuscular complications during or after the acute phase of infection. Direct viral infection and immune-mediated mechanisms have been hypothesized. Furthermore, in patients with underlying autoimmune neuromuscular diseases, COVID-19 infection may trigger a disease flare. COVID-19 vaccines appear to be safe and effective at preventing severe illness from COVID-19. Certain vaccines are associated with an increased risk of Guillain-Barré syndrome and possibly Bell's palsy, but the absolute incidence is low, and benefits likely outweigh the risks. Newer prophylactic therapies and treatments are also becoming available for patients who may not mount a sufficient response to vaccination or have contraindications. In this article, we discuss the current available evidence on neuromuscular complications of COVID-19 and clinical considerations regarding vaccination.

Neuromuscular complications of coronavirus disease-19.

PURPOSE OF REVIEW: Since its outbreak in Wuhan, China in late 2019, coronavirus disease-19 (COVID-19) has become a global pandemic. The number of affected cases and deaths continues to rise. Primarily a respiratory illness, COVID-19 is now known to affect various organ systems including peripheral nerve and skeletal muscle. The purpose of this review is to discuss the scope of neuromuscular manifestations and complications of COVID-19. RECENT FINDINGS: Several neuromuscular conditions, including Guillain-Barré syndrome, rhabdomyolysis, and myositis, have been reported in patients infected with COVID-19, but even with a temporal association, a causal relationship remains unproven. Direct invasion of neurons or myocytes by the virus, and immune-mediated injury have been speculated but not consistently demonstrated. In addition to potentially causing the above conditions, COVID-19 can trigger exacerbations of preexisting neuromuscular conditions such as myasthenia gravis, and severe infections can lead to critical illness myopathy/polyneuropathy. SUMMARY: COVID-19 appears to be potentially associated with a wide range of neuromuscular manifestations and complications. Further studies are needed to examine these possible associations, understand the pathogenesis, and develop preventive and treatment strategies.

Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19.

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).