Sex Differences on Cerebrovascular Complications in Hospitalized COVID-19 Patients: A Meta-analysis
Bradley Ong1, Lea Elora Conda 2, Ken Uchino3, Tereynz Mendoza4, Adrian Hernandez-Diaz5, Sung Cho6
1Cleveland Clinic Main Campus - Neurological Institute, 2Ateneo School of Medicine and Public Health, 3Cleveland Clinic Foundation, 4Waseda University, 5University of Connecticut School of Pharmacy, 6Johns Hopkins Hospital
Objective:
We aimed to investigate whether sex differences impact risk of development of ischemic(IS) and hemorrhagic stroke(HS) among hospitalized COVID-19 patients.
Background:
Risk of vascular events is associated with Coronavirus Disease 19(COVID-19) with variable rate of acute stroke. Data indicate that COVID-19-related stroke disproportionately affects males. Pre-pandemic studies show that stroke is higher among females. Whether these data reflect underlying sex-specific biological differences, recruitment biases, or confounding factors is unclear.
Design/Methods:
Systematic search of MEDLINE(PubMed) and six other databases was done from inception to April 2023. Studies were included if they enrolled both hospitalized adult males and females with active COVID-19 disease and reported prevalence of stroke with sex stratification. Composite stroke included earliest hospital admission with stroke occurrence or death with stroke as underlying cause. We define risk ratio as the cumulative incidence of type of stroke in males over the cumulative incidence of the same stroke in females.
Results:
We included 19 studies encompassing 135,892 patients(median age=63 years,48.7% males), of which 1,585(1.2%) had a stroke with IS being the most common(53.4%,n=841/1,585), followed by unspecified stroke(29.7%,n=471/1,585), and HS(17.3%,n=274/1,585).
We found that there is higher proportion of males(17%;95%CI = 15%-19%) than females(8%;CI=7%-10%) who developed composite stroke. There was also two-fold greater proportion of males(18%; 95%CI=15%-20%) having IS than females(9%;CI=7%-11%). Males(5%;CI=3%-7%) also had higher risk of HS compared to females(1%;CI=0%-2%). Lastly, we find that males(2%;95%CI=0%-3%) and females(2%;95%CI=0%-3%) have equal proportions of having unspecified stroke.
Overall, males had an increased risk of developing composite stroke compared to females(RR=1.26;95%CI=1.07-1.48). Males also had a higher risk of HS compared to female(RR=1.65;95%CI=1.232.21). The risk of developing IS was similar between the groups(RR=1.15;95%CI=0.98-1.35).
Conclusions:
Males had higher proportion of developing stroke. Males also had increased risk of acute stroke during COVID-19 hospitalization, especially hemorrhagic strokes. Further studies are needed on the mechanism of male sex and stroke among hospitalized COVID-19 individuals.