Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures.

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.

Objective: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID‐19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes.Methods: We identified 197 patients with COVID‐19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes.Results: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51,p= 0.01) and NCSE (27.3% vs 4.3%, OR 8.34,p= 0.01). A pre‐existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33,p= 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in‐hospital mortality (hazard ratio [HR] 4.07 [1.44–11.51],p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03–0.33] vs 0.43 [0.36–0.49]).Interpretation: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID‐19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872–883