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Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients

Our take —

In this case series of 509 patients hospitalized in Chicago with COVID-19, neurologic manifestations were common (e.g. myalgias, headache, dysgeusia, anosmia, encephalopathy): 42% of patients had at least one at symptom onset, and 82% experienced one at any time during COVID-19. The only neurologic manifestation associated with clinical outcomes was encephalopathy. More research into the causal relationship between neurologic symptoms and COVID-19 outcomes, and on the long-term effects of neurologic manifestations during COVID-19 are needed.

Study design

Case Series, Retrospective Cohort

Study population and setting

This study tested the association of neurologic manifestations of COVID-19 with clinical outcomes among 509 hospitalized patients with PCR-confirmed SARS-CoV-2 infection, who were consecutively admitted to one of the ten centers within the Northwestern Medicine Healthcare system in Chicago from March 5 to April 6, 2020. Data on demographics, comorbidities, disease course, and labs were extracted from electronic medical records. COVID-19 disease severity was defined as severe vs. non-severe, based on need for any mechanical ventilation during hospitalization. Neurologic manifestations were considered from symptom onset though 90 days. The main outcome of interest was functional outcome at hospital discharge, defined by the modified Rankin Scale (mRS) with a range from 0 (able to look after oneself without assistance) to 6 (death).

Summary of Main Findings

Among 509 patients hospitalized with COVID-19 (mean age 58.5 years, 55% male, 26% with severe disease), 42% had neurologic manifestations at COVID-19 onset, 63% at hospital admission, and 82% at any time during disease course. At COVID-19 onset, the most frequent neurologic manifestations were myalgia (body aches), headache, and dysgeusia (distortion of taste), experienced by 26%, 17%, and 5% of people, respectively. At any time during the clinical course, 45% of participants had myalgia, 38% had headache, 32% had encephalopathy (altered mental status, confusion, depressed level of consciousness), 30% experienced dizziness/vertigo, and 16% had dysgeusia. Other than encephalopathy, which was considerably more common among individuals with severe COVID-19 (84% vs. 13% in non-severe cases), the distribution of neurologic manifestations were similar between severe and non-severe patients. Encephalopathy was the only neurologic outcome associated with worse favorable outcome and greater mortality, after adjusting for a range of covariates including COVID-19 severity, sex, history of neurologic disorder, time from COVID-19 onset to hospitalization, academic medical center hospitalization, and race.

Study Strengths

Neurologic manifestations and functional outcomes were decided by consensus of two independent reviewers.


This study does not demonstrate that encephalopathy is a cause of poor clinical outcomes; for example, it is possible that clinical deterioration due to COVID-19, or therapies received during hospitalization, caused encephalopathy. A broad range of neurologic manifestations were considered, which have differing severity and role in clinical presentation and outcomes; considering them all together may hide heterogeneities in specific manifestations. Fewer than 6% of patients were evaluated by neurologists or neurosurgeons, so it is possible that neurologic manifestations were under- or mis-reported. Additionally, assessing temporality is limited by self-report of symptoms present at time of COVID-19 onset (i.e., it is unknown whether neurologic symptoms preceded COVID-19 diagnosis). The study included multiple sites in the Chicago area but only included hospitalized patients; thus, the degree to which the results are generalizable to other populations, including those with mild disease, is unclear. The study did not examine long-term consequences of these neurologic manifestations.

Value added

This relatively large and multi-site case series is one of the few studies to specifically examine neurologic symptoms as a predictor of disease severity.

This review was posted on: 29 October 2020