Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants

Abstract

Background and objectives: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome.

Methods: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death.

Results: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%).

Discussion: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

Figure 1. Incidence Dynamics of Neuro-COVID Disorders

Intrapandemic incidence of neuro-COVID cases (A) and their proportion relative to all hospitalized COVID cases (B; each dot represents a recruiting center). Incidence is represented separately for selected self-reported neurologic symptoms (C) and clinical neurologic syndromes (D). COVID = coronavirus disease.

Figure 2. COVID-Related Severe Respiratory Failure and Incidence of Neuro-COVID Disorders

LOWESS was used to represent graphically the proportion of patients with severe respiratory failure, per week (colored area). Incident neuro-COVID cases are represented shaded in gray. COVID = coronavirus disease; LOWESS = locally weighted scatterplot smoothing.

Figure 3. Frequency, Onset, and Long-term Functional Outcome of Neuro-COVID Disorders

Frequency and onset are represented as absolute number of cases (A) while functional outcome categories are represented as % of cases (B). ADL = activities of daily living; COVID = coronavirus disease.

Figure 4. Recovery and Survival Curves of Selected Neuro-COVID Disorders

Recovery curves of cognitive impairment and hyposmia-hypogeusia (A) and survival curves of acute encephalopathy and acute ischemic stroke (B). Dynamics of good functional outcome is shown for all recruited cases (C). COVID = coronavirus disease.