Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis
BACKGROUND AND OBJECTIVES There is accumulating evidence supporting an association between the "thrombosis and thrombocytopenia syndrome" (TTS) and adenovirus vector-based vaccines against SARS-CoV-2. Yet, TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS We performed a systematic review and meta-analysis of clinical trials, cohorts, case series and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with post-vaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were further included in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95%CI:36-66%; I(2)=61%). TTS was independently associated with a higher likelihood of CVST, when compared to non-TTS patients with thrombotic events after vaccination (OR:13.8; 95%CI:2.0-97.3; I(2)=78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95%CI:21-36%) and 38% (95%CI:27-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval:10 days; 95%CI:8-12) and affected predominantly women (69%, 95%CI:60-77%), under the age of 45, even in the absence of pro-thrombotic risk factors. DISCUSSION Approximately one half of TTS cases present with CVST, while almost one third of TTS patients do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION The pre-specified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).