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

Maria-Ioanna Stefanou; Lina Palaiodimou; Diana Aguiar de Sousa; Aikaterini Theodorou; Eleni Bakola; Dimitrios Eleftherios Katsaros; Panagiotis Halvatsiotis; Elias Tzavellas; Androniki Naska; Jonathan M Coutinho; Else Charlotte Sandset; Evangelos J Giamarellos-Bourboulis; Georgios Tsivgoulis

doi:10.1212/WNL.0000000000200996

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

Neurology. 2022 Oct 3;99(14):e1465-e1474. doi: 10.1212/WNL.0000000000200996.

Affiliations

¹ From the Second Department of Neurology (M.-I.S., L.P., A.T., E.B., D.E.K., G.T.), "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurosciences (Neurology) (D.A.d.S.), Hospital de Santa Maria, University of Lisbon, Portugal; Second Department of Internal Medicine-Propaedeutic and Diabetes Center (P.H.), Medical School, University General Hospital "Attikon," First Department of Psychiatry (E.T.), Aiginition Hospital, and Department of Hygiene (A.N.), Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurology (J.M.C.), Amsterdam University Medical Centers, the Netherlands; Department of Neurology (E.C.S.), Stroke Unit, Oslo University Hospital, Norway; 4th Department of Internal Medicine (E.J.G.-B.), Medical School, National and Kapodistrian University of Athens, Greece; and Department of Neurology (G.T.), University of Tennessee Health Science Center, Memphis.
² From the Second Department of Neurology (M.-I.S., L.P., A.T., E.B., D.E.K., G.T.), "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurosciences (Neurology) (D.A.d.S.), Hospital de Santa Maria, University of Lisbon, Portugal; Second Department of Internal Medicine-Propaedeutic and Diabetes Center (P.H.), Medical School, University General Hospital "Attikon," First Department of Psychiatry (E.T.), Aiginition Hospital, and Department of Hygiene (A.N.), Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurology (J.M.C.), Amsterdam University Medical Centers, the Netherlands; Department of Neurology (E.C.S.), Stroke Unit, Oslo University Hospital, Norway; 4th Department of Internal Medicine (E.J.G.-B.), Medical School, National and Kapodistrian University of Athens, Greece; and Department of Neurology (G.T.), University of Tennessee Health Science Center, Memphis. tsivgoulisgiorg@yahoo.gr.

PMID: 36002319
DOI: 10.1212/WNL.0000000000200996

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.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Arteries
COVID-19* / epidemiology
COVID-19* / prevention & control
Humans
Ischemic Stroke* / epidemiology
Ischemic Stroke* / etiology
RNA, Messenger
Syndrome
Vaccination / adverse effects

Substances

RNA, Messenger