Acute Arterial Ischemic Stroke Following COVID-19 Vaccination: A Systematic Review and Meta-analysis

Abstract

Background and objectives: Acute arterial ischemic stroke (AIS) has been reported as a rare adverse event following coronavirus disease 2019 (COVID-19) vaccination with messenger RNA (mRNA) or viral vector vaccines. However, data are sparse regarding the risk of postvaccination AIS and its potential association with thrombotic-thrombocytopenia syndrome (TTS).

Methods: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts, and case-series was performed with the aim to calculate the following: (1) the pooled proportion of patients presenting with AIS following COVID-19 vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; and (3) the proportion of TTS among postvaccination AIS cases. Patient characteristics were assessed as secondary outcomes.

Results: Two RCTs, 3 cohort studies, and 11 registry-based studies comprising 17,481 AIS cases among 782,989,363 COVID-19 vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19 vaccine type was 4.7 cases per 100,000 vaccinations (95% CI 2.2-8.1; I ² = 99.9%). The pooled proportion of AIS following mRNA vaccination (9.2 cases per 100,000 vaccinations; 95% CI 2.5-19.3; I ² = 99.9%) did not differ compared with adenovirus-based vaccination (2.9 cases per 100,000 vaccinations; 95% CI 0.3-7.8; I ² = 99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA-based or vector-based vaccination. The pooled proportion of TTS among postvaccination AIS cases was 3.1% (95% CI 0.7%-7.2%; I ² = 78.8%).

Discussion: The pooled proportion of AIS following COVID-19 vaccination is comparable with the prevalence of AIS in the general population and much lower than the AIS prevalence among severe acute respiratory syndrome coronavirus 2-infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.