Safety, reactogenicity, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for a living systematic review and meta-analysis

Abstract

Abstract Background Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding safety of these vaccines for the pregnant persons and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, efficacy or effectiveness, reactogenicity, and immunogenicity of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review (LSR) of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide information necessary to help guide vaccine policy decisions. Methods We aim to conduct a LSR based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety (i.e., impacts on obstetric and neonatal outcomes), efficacy or effectiveness of COVID-19 vaccines in pregnant persons. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including pre-specified subgroup and sensitivity analyses, and will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to evaluate the certainty of evidence. Conclusion This will be the first living systematic review (LSR) and meta-analysis assessing the safety, reactogenicity, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons. An online interactive dashboard for data visualization using Microsoft Power BI will be developed to regularly update and disseminate the latest findings (an in-progress version is available at https://safeinpregnancy.org/lsr/). In addition, the findings will be disseminated through publications and presentations.