The Changes in COVID-Related Neurologic Symptoms, Outcomes Across First 3 Waves

Long-term functional outcome was favorable in most COVID-related neurologic disorders, but mild symptoms typically lasted more than 6 months after infection.

Incidence of COVID-related neurologic manifestations decreased during the first 3 waves of the COVID-19 pandemic with positive long-term functional outcomes observed after 6 months in most patients with neurologic symptoms, according to study findings published in Neurology.

Researchers in Italy conducted a multicenter, observational, cohort study in 38 centers across Italy and the Republic of San Marino to determine the incidence of neurologic disorders among individuals hospitalized with COVID-19 between March 2020 and June 2021 and their long-term functional outcomes after 6 months.

During the first 70 weeks of the prevaccination phase of the pandemic, 52,759 patients were hospitalized with confirmed COVID-19 infection and 1865 of these patients developed 2881 new neurologic disorders due to COVID-19 infection.

Neurologic disorders included acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), cognitive impairment (13.7%), headaches (11.8%), Guillain Barré syndrome (GBS; 7.2%), seizures or status epilepticus (7.2%), hemorrhagic stroke (3%), dizziness (2.6%), and encephalitis (1.9%).

Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic.

The majority of these neurologic disorders developed during the prodromic phase (44.3%) or acute respiratory illness phase (40.9%) of COVID-19 infection. In contrast, cognitive impairment manifested during the recovery phase (48.4%).

Incidence of neurologic manifestations of COVID-19 infection declined during the various waves of the pandemic, peaking at 8.4% during the first wave with significant reductions during the second and third waves (5.0% and 3.3% incidences, respectively; P =.027)

Long-term function outcomes for 1601 (85.8%) of these 1865 patients were subdivided into 4 categories — full recovery, mild residual symptoms, disabling symptoms, or death after 6 months.

The vast majority (64.6%) of hospitalized patients with neurologic symptoms progressed with good functional outcomes — either making a full recovery or reporting only mild residual symptoms after 6 months. Approximately 28.1% patients reported continuing mild symptoms, usually related to cognitive impairment (56.2%) and dizziness (42.8%).

A small fraction of individuals (5.7%) continued to report long-term, disabling symptoms — most frequently manifesting among patients who survived stroke (47.6%), but also among those who had encephalitis, acute encephalopathy, and GBS.

Good functional outcomes improved during the study period (r=0.29; 95% CI, 0.05-0.50; P =.019). Age and severe respiratory failure independently predicted poor functional outcomes, whereas treatment of COVID-19 infection with remdesivir predicted good functional outcomes.

“Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic,” the researchers wrote. “Long-term functional outcome was favourable in most neuro-COVID disorders, although mild symptoms commonly lasted over 6 months after infection,” they added.

Study limitations included potential missed diagnosis of mild neurologic symptoms, including transient headache or mild confusion, that did not warrant examination by a neurologist.

This article originally appeared on Neurology Advisor


Beretta S, Cristillo V, Camera G, et al. Incidence and long-term functional outcome of neurologic disorders in hospitalized COVID-19 patients infected with preomicron variants. Neurology. Published online July 6, 2023:10.1212/WNL.0000000000207534. doi:10.1212/WNL.0000000000207534