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

Abstract

Objective: Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19.

Methods: We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression.

Results: Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001).

Interpretation: Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

Figure 1

Parsimoniously Adjusted Models of Encephalopathy Occurrence and Favorable Discharge Functional Outcome (Modified Rankin Scale Score 0–2). (A) Parsimoniously adjusted model of encephalopathy occurrence. A priori variables included: severe COVID‐19 disease; age; history of any neurological disorder; time from COVID‐19 onset to hospitalization; serum white blood cell count; number of neurologic manifestations at COVID‐19 onset; occurrence of anosmia, dysgeusia, or headache at COVID‐19 onset; male sex; C‐reactive protein; and D‐dimer. In addition to the a priori variables, the following variables were univariately associated with encephalopathy at P ≤ 0.15 and were considered in the backward stepwise Akaike Information Criteria algorithm used to generate the parsimonious model: history of smoking, dyslipidemia, diabetes mellitus, hypertension, cerebrovascular disease, peripheral vascular disease, chronic kidney disease, heart failure, cancer, and organ transplantation; and procalcitonin level. Only those variables that satisfied the Akaike Information Criteria algorithm for parsimonious model inclusion are listed. (B) Parsimoniously adjusted model of favorable functional outcome at discharge (modified Rankin Scale Score 0 to 2). A priori variables included: age, severe COVID‐19 disease, occurrence of encephalopathy, male sex, history of any neurological disorder, academic medical center hospitalization, time from COVID‐19 onset to hospitalization, and race. In addition to the a priori variables, the following variables were univariately associated with encephalopathy at P ≤ 0.15 and were considered in the backward stepwise Akaike Information Criteria algorithm used to generate the parsimonious model: ethnicity; history of heart failure, organ transplantation, smoking, dyslipidemia, hypertension, cerebrovascular disease, peripheral vascular disease, coronary artery disease, chronic kidney disease, and cancer. Only those variables that satisfied the Akaike Information Criteria algorithm for parsimonious model inclusion are listed.