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Up to one-third of COVID-19 patients experienced at least 1 neurologic manifestation, and about 2% experienced stroke, according to a systematic review and meta-analysis published in Neurology.

Studies have showed COVID-19 impacts the central nervous, peripheral nervous and musculoskeletal systems of patients, and cases involving neurologic symptoms are increasing, according to the researchers. They sought to determine the manifestations’ association with COVID-19 severity and mortality.

They searched for observational studies published in 2020 in PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library, and ClinicalTrials.gov that reported at least 1 new onset neurologic manifestation due to confirmed and probable cases of COVID-19. They assessed the studies’ risk of bias utilizing the Joanna Briggs Institute (JBI) tool and controlled the false discovery rate (FDR) with the Benjamini-Hochberg procedure.

A total of 350 studies involving 55 countries were included in the systematic review. Of the 145,721 COVID-19 cases identified, 129,786 involved hospitalizations. Most (84.6%) of the studies had low risk of bias: 14% percent had moderate risk, and 1.4% had high risk.

The most common of 24 identified neurologic symptoms were fatigue (32%), myalgia (20%), myalgia or fatigue (31%), headache (13%), dizziness (7%), headache and dizziness together (12%), smell impairment (19%), taste impairment (21%), smell or taste impairment (18%), acute confusion/delirium (11%), disturbance of consciousness (7%), and agitation (45%).

Thirty-three studies involved 17 neurologic diagnoses. The most common neurologicdiagnosis was stroke (pooled prevalence across 29 studies 2%). This included 1% ischemic stroke or transient ischemic attack, 0.31% hemorrhagic stroke, and 0.12% cerebral venous thrombosis. Across 3 studies, 24% of cases involved neuropsychiatric disorders. In 4 studies, 5% of cases involved skeletal muscle injury.

Across 48 studies (2829 severe cases and 7493 non-severe cases), the researchers found that skeletal muscle injury/damage in 2 studies (OR 3.29), disturbance of consciousness (OR 5.68) in 4 studies, and fatigue (OR 1.27) in 33 studies were linked with severe COVID-19. They found that patients who had severe COVID-19 were less likely to have alterations in smell (OR 0.44, 8 studies) and taste (OR 0.62, 5 studies) compared with patients with mild cases.

Among COVID-19 patients aged at least 60 years (n=3176 hospitalized patients), the most common symptom was acute confusion/delirium (34%, 5 studies), followed by fatigue (20%, 9 studies), and myalgia (11%, 10 studies). In pediatric patients (3051 hospitalized, 20 studies), fatigue or myalgia (17%, 2 studies), smell or taste impairment (13%, 2 studies), and headache (10% 13 studies) were the most common.

Across 13 studies that identified neurologic symptoms in non-hospitalized cases, patients who were not hospitalized were more likely to experience smell impairment (50%), taste impairment (44%), headache (31%), and myalgia (31%). Hospitalized patients were more likely to experience fatigue (31%) and myalgia or fatigue (30%).

In 21 studies that assessed mortality, 770 of 2982 patients who at least 1 neurologic symptom died (pooled prevalence 27%). In patients aged at least 60 years, those with neurologic symptoms were more likely to die (OR 1.80, 13 studies).

Study limitations included little data from prospective studies, lack of uniformity of diagnostic criteria for neurologic manifestations, large inclusion (89%) of hospitalized cases, and confounding bias.

The researchers concluded, “In those over 60, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.