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

Background and objective: A variety of neurological disorders has been reported as presentations or complications of 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 multicentre, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurological 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 to June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms or death. Results: Among 52759 hospitalized COVID patients, 1865 patients presenting 2881 new neurological disorders associated with COVID-19 infection (neuro-COVID) were recruited. Incidence of neuro-COVID cases significantly declined over time, comparing the first three 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 neurological disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%) and cognitive impairment (13.7%). The onset of neurological 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 the majority of neuro-COVID patients (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 pre-vaccination phase of the pandemic. Long-term functional outcome was favourable in most neuro-COVID disorders, although mild symptoms commonly lasted over 6 months after infection.