Sex differences on cerebrovascular complications in hospitalized COVID-19 patients: a meta-analysis

Although pre-pandemic data suggest a higher stroke incidence in females, recent evidence suggests COVID-19-related strokes disproportionately affect males. Prior studies often analyzed stroke as a composite outcome without stratifying by biologically distinct subtypes. This systematic review and meta-analysis evaluated sex differences in the risk of ischemic and hemorrhagic stroke among hospitalized patients with COVID-19.

We searched MEDLINE and six additional databases from inception to December 2024. We included observational studies enrolling adults (≥18 years) with active COVID-19 infection, hospitalized, and reporting sex-stratified stroke outcomes. Pooled risk ratios (RRs) for each stroke subtype were calculated using random-effects models. We defined RR as the ratio of the cumulative incidence of type of stroke in males over the cumulative incidence of the same type of stroke in females.

Seventeen studies comprising 135,481 hospitalized COVID-19 patients (mean age 63.3 years; 48.7% male) met inclusion criteria. Stroke occurred in 1,509 patients (1.1%), with ischemic stroke accounting for 53.9% of cases, unspecified stroke for 30.1%, and hemorrhagic stroke for 16.1%. Males accounted for a greater proportion of stroke cases across all subtypes: 63.1% of ischemic, 69.0% of hemorrhagic, and 59.0% of unspecified strokes. The estimated prevalence of ischemic stroke was 17% in males (95% CI, 15%-20%) versus 9% in females (95% CI, 7%-11%), and hemorrhagic stroke occurred in 4% of males (95% CI, 2%-6%) versus 1% of females (95% CI, 0%-2%). Unspecified stroke occurred in 2% of both sexes (95% CI, 0%-3%). Pooled risk estimates showed that males had a significantly higher risk of any stroke (RR = 1.25; 95% CI,1.05-1.50), driven by an elevated risk of hemorrhagic stroke (RR = 1.64; 95% CI, 1.06-2.54). The increased risk of ischemic stroke in males did not reach statistical significance (RR = 1.18; 95% CI, 0.97-1.44).

This is the first meta-analysis to stratify stroke risk by sex and stroke subtype in hospitalized COVID-19 patients. Males were at significantly higher risk for hemorrhagic stroke, suggesting possible sex-specific vulnerability that warrants further studies.