ABSTRACT
Objective: To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningo-encephalitis) among patients hospitalized with coronavirus disease 2019 (COVID-19). Background: Though case series abound, limited prospective multi-center data exists describing neurologic manifestations of COVID-19 Design/Methods: Prospective observational study of hospitalized adults in 179 hospitals in 24 countries with laboratory-confirmed SARS-CoV-2 infection within the SCCM Discovery Viral Infection and Respiratory Illness University Study (VIRUS) COVID-19 Registry Results: Of 16,225 patients enrolled in the registry with discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations were older with median (IQR) age 72 (61.0-81.0) vs. 61 (48.0-72.0) years and had higher prevalence of chronic medical conditions, including vascular risk factors. Systemic viral symptoms (fever, dyspnea, and cough) were less commonly reported in patients with severe neurologic manifestations as were milder neurologic symptoms including anosmia, dysgeusia, and headache. Adjusting for sex and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (OR 1.82, p<0.001) as defined by the WHO ordinal disease severity scale. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR 1.45, p<0.001) and ICU interventions (ECMO: OR 1.78, p=0.009 and RRT: OR 1.99, p<0.001). Hospital and 28-day mortality for patients with neurologic manifestations was higher (OR 1.51 and 1.58, p<0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (OR -0.84, -1.34, and -0.84, p<0.001). Conclusions: Encephalopathy at admission is common in COVID-19 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.