Thrombotic and thromboembolic events, with or without thrombocytopenia, following viral vector-based COVID-19 vaccines administration: a systematic review protocol

Background Viral vector-based COVID-19 vaccines have proven to be effective and safe in clinical trials and post-authorization studies. Although infrequent, some serious thrombotic and thromboembolic events following immunization have emerged, and causality assessment committees must consider and critically assess different sources of evidence to inform their decisions about whether these events supposedly attributable to vaccination or immunization (ESAVI) are associated with the vaccine or are coincidental. Therefore, this systematic review aims to gather information on the association and biological mechanisms between thrombotic and thromboembolic events, with or without thrombocytopenia, and the administration of viral vector-based COVID-19 vaccines. Methods We will conduct a systematic review following the evidence synthesis framework proposed by the Pan American Health Organization to support the ESAVI causality assessment. We will search for primary clinical and preclinical studies in the Epistemonikos’ COVID-19 L.OVE (Living Overview of the Evidence) repository, a comprehensive and validated source of COVID-19 evidence. We will include studies reporting any thrombotic or thromboembolic event, with or without thrombocytopenia, after the administration of a viral vector-based COVID-19 vaccine. The screening and data extraction will be performed by two independent authors. We will assess the risk of bias by two reviewers using the appropriate tool for each study design. Discrepancies will be discussed or resolved by a third author. We will use GRADE to assess the certainty of evidence for clinical studies and prepare summary of findings tables. For individual-based (case series and case reports) and preclinical studies, we will summarize the results in descriptive tables. Expected results and implications This will be the first systematic review using the evidence synthesis framework for ESAVI causality assessment, currently under validation by the Pan American Health Organization and the Epistemonikos Foundation. By gathering clinical and preclinical evidence, it is expected to inform about the risks of thromboembolic events following vaccination with viral vector-based COVID-19 vaccines, and also the possible underlying biological mechanisms. Policymakers, such as safe vaccination committees, and other evidence synthesis authors could replicate this novel methodology to strengthen the evidence-based ESAVI causality assessment.