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

Dr. Stefanou et al. analyzed the risk of acute ischemic stroke (AIS) after COVID-19 vaccination and its potential association with thrombotic-thrombocytopenia syndrome (TTS) in a systematic review and meta-analysis of 2 randomized-controlled trials (RCTs), 3 cohort studies, and 11 registry-based studies. They found 17,481 AIS cases among 782,989,363 COVID-19 vaccinations, giving a pooled proportion of postvaccination AIS of 4.7 cases per 100,000 vaccinations, with no difference observed between mRNA-based and adenovirus-based vaccinations. The pooled proportion of TTS in AIS cases was 3.1%. In response, Dr. Du notes that the rate of AIS cases was lower than the age-standardized global AIS prevalence and incidence rates per 100,000 individuals per year, suggesting that the vaccinations may be associated with a lower risk of AIS. In this regard, Dr. Du cites a previous study that found a significant association between COVID-19 vaccination and lower risks of myocardial infarction and ischemic stroke. Responding to these comments, the authors caution that their crude estimate of new AIS events per 100,000 vaccination, without age standardization or annualization, was not directly comparable with age-standardized AIS estimates per 100,000 individuals per year in the general population. These exchange raises demonstrate relevant complexities when seeking to compare the risk of postvaccination AIS with the “background” risk in the general population while motivating additional studies to investigate whether COVID-19 vaccination might reduce AIS risk at a population level. Dr. Stefanou et al. analyzed the risk of acute ischemic stroke (AIS) after COVID-19 vaccination and its potential association with thrombotic-thrombocytopenia syndrome (TTS) in a systematic review and meta-analysis of 2 randomized-controlled trials (RCTs), 3 cohort studies, and 11 registry-based studies. They found 17,481 AIS cases among 782,989,363 COVID-19 vaccinations, giving a pooled proportion of postvaccination AIS of 4.7 cases per 100,000 vaccinations, with no difference observed between mRNA-based and adenovirus-based vaccinations. The pooled proportion of TTS in AIS cases was 3.1%. In response, Dr. Du notes that the rate of AIS cases was lower than the age-standardized global AIS prevalence and incidence rates per 100,000 individuals per year, suggesting that the vaccinations may be associated with a lower risk of AIS. In this regard, Dr. Du cites a previous study that found a significant association between COVID-19 vaccination and lower risks of myocardial infarction and ischemic stroke. Responding to these comments, the authors caution that their crude estimate of new AIS events per 100,000 vaccination, without age standardization or annualization, was not directly comparable with age-standardized AIS estimates per 100,000 individuals per year in the general population. These exchange raises demonstrate relevant complexities when seeking to compare the risk of postvaccination AIS with the “background” risk in the general population while motivating additional studies to investigate whether COVID-19 vaccination might reduce AIS risk at a population level.