Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies

Abstract

Background: We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke.

Methods: We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods.

Results: Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75-.90]) and HS (IRR, 0.75 [95% CI, .67-.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70-1.98]). SCCS identified increased risks 1-21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00-1.10]; IRRHS, 1.16 [95% CI, 1.06-1.26]) or 1-28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00-1.08]; IRRHS, 1.37 [95% CI, 1.15-1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08-2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1-7.2]).

Conclusions: Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.

Keywords: COVID-19; meta-analysis; real-world study; stroke; vaccination.