Approximately 13% of hospitalized COVID patients have serious neurologic symptoms


It has been established that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes dysfunction throughout the body, including the nervous system. Even in patients with moderate acute disease, neurologic symptoms may be encountered. In some cases, these manifestations may persist due to long-haul coronavirus disease, also known as long-COVID.

Case series, single health system studies, and administrative database studies have shown more serious neurologic symptoms in hospitalized patients, including stroke. In a recent study in the journal Critical Care Explorations, the Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry was used to record significant neurologic signs of SARS-CoV-2 infection, as well as prehospital risk factors and outcomes.

OBSERVATIONAL STUDY Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic. Image Credit: Donkeyworx / Shutterstock

What did they do?

The VIRUS: COVID-19 Registry holds de-identified, Health Insurance Portability and Accountability Act (HIPAA) compliant data on patients who have been hospitalized with SARS-CoV-2 infection. Research Electronic Data Capture, a secure web-based program and operational technique for electronic collection and processing of research data, was used by study sites to enter the data.

Between March 25, 2020, and March 9, 2021, a multi-national prospective, cross-sectional, observational study of hospitalized adult patients with SARS-CoV-2 infection was conducted. Patients were included if they had PCR-confirmed SARS-CoV-2 within 21 days of admission to hospital.  Information from the registry was used to identify patients who were suffering from encephalopathy at the time of their admission.

Encephalopathy during hospitalization was not recorded due to concerns about several confounders that are common in hospitalized patients, as well as the possibility of inaccurate data collection. As admission diagnoses or hospital complications, seizure, stroke, and meningitis/encephalitis were evaluated. Registry data was used to collect patient demographics, comorbidities, medication use, critical care interventions, hospital problems, and clinical outcomes.

What did they find?

From March 25, 2020, to March 9, 2021, the VIRUS registry enrolled 65,850 hospitalized adult patients. There were 16,225 participants included in the analysis because they had information on 28-day outcomes or hospital discharge mortality. A total of 2,092 individuals had severe neurologic symptoms, with 1,840 being diagnosed at the time of admission. At admission, 1,656 patients had been found to have encephalopathy. At the time of admission or while in the hospital, 414 patients had a stroke, a seizure, or meningitis/encephalitis. Stroke was recorded in 331 individuals, seizures in 243 patients, and meningitis/encephalitis in 73 patients.

Neurologic symptoms were more common in older patients. Men and women both experienced neurological symptoms. When compared to White patients, Black patients had a higher likelihood of acquiring neurologic symptoms, while South Asian patients had a lower likelihood. Medical comorbidities were more common in those with neurologic symptoms.

Patients with neurologic symptoms had increased odds of undergoing extracorporeal membrane oxygenation (ECMO) and renal replacement treatment (RRT) and were less likely to undergo prone position after adjusting for age, sex, and time since the pandemic began. Patients suffering a stroke had a 3.20 chance of needing ECMO and a 3.23 chance of needing RRT, but there was no difference in proning. Patients who suffered seizures were 2.78 times more likely to require ECMO. In patients with encephalopathy at admission, RRT was more likely to be required, but proning was less likely.

Patients with neurologic symptoms were more likely to require ICU admission, had a higher mortality rate, and had fewer ICU, hospital, and ventilator-free days. Encephalopathy patients were more likely to be admitted to the ICU and had a higher fatality rate.

Meningitis/encephalitis was linked to a higher risk of ICU admission and fewer hospital, ICU, and ventilator-free days, but not to a higher risk of death.

A proportional odds regression analysis adjusted for age, sex, and time since the pandemic began revealed that disease severity increased for patients with neurologic signs. The highest risk of more severe disease was associated with patients with meningitis/encephalitis, while encephalopathy and seizures also increased the risk.


Patients with SARS-CoV-2 infection frequently develop encephalopathy upon admission to the hospital, although more significant neurologic signs are uncommon. All severe neurologic symptoms are linked to poorer outcomes, including a higher risk of mortality. There is still a need for more research to understand which people are most at risk for neurologic manifestations, the underlying pathophysiology of these manifestations, and how to prevent and treat these manifestations.