Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis.

Background and Objectives: One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality. Methods: We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. Results: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91). Discussion: Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological 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.