Thrombotic and cerebrovascular events following SARS-CoV-2 vaccination: an umbrella review of systematic reviews and meta-analyses

Abstract

Rare thrombotic and cerebrovascular events have been reported after SARS-CoV-2 vaccination, raising safety concerns. This umbrella review synthesizes evidence from 19 systematic reviews and meta-analyses examining thrombotic outcomes, including acute ischemic stroke and cerebral venous sinus thrombosis, across different vaccine platforms. Methodological quality was assessed using AMSTAR-2, and findings were synthesized by outcome and platform. Evidence consistently shows that thrombotic and cerebrovascular events following vaccination are rare. mRNA vaccines (BNT162b2, mRNA-1273) were not associated with increased risk beyond background population rates. Adenoviral vector vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S) were linked to a rare syndrome of vaccine-induced immune thrombotic thrombocytopenia, most commonly presenting as cerebral venous sinus thrombosis in younger adults. Evidence for whole-virus vaccines was limited but did not indicate consistent safety concerns. Across all platforms, thrombotic risk was substantially lower than that from SARS-CoV-2 infection. Overall, vaccination benefits outweigh risks, highlighting the importance of ongoing surveillance and transparent communication.