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.