Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-Analysis

Abstract

Importance: To our knowledge, no comprehensive meta-analysis has been published focusing on the safety, tolerability, and immunogenicity of current coronavirus disease 2019 (COVID-19) vaccine candidates, although numbers of basic research and clinical trial results have been announced.Objective: To summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Data Sources: PubMed, the Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 9830 articles were identified initially and 43 were retrieved for more detailed evaluation.Study Selection: Five randomized, double-blind, placebo-controlled trials were selected.Data Extraction and Synthesis: Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a random-effects model if statistical heterogeneity was present.Main Outcomes and Measure: Main outcomes measures of our meta-analysis included safety and immunogenicity of the vaccine. The safety outcomes were evaluated as local adverse reactions and systemic adverse reactions. Immunogenicity outcomes were mainly evaluated by IgG or other specific antibody responses to the receptor binding domain, and neutralizing antibodies to live SARS-CoV-2.Results: According to the results, there is an increase in total adverse events for subjects with either low or high dose vaccination, compared with placebo controls (P P = 0.0002 and P P P Conclusion and Relevance: Our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.Funding: This work was supported in part by research grants from the Major Research plan of the National Natural Science Foundation of China (No. 91949204 to J.C.Z.), the State Key Program of the National Natural Science Foundation of China (No. 81830037 to J.C.Z.), the National Basic Research Program of China (973 Program Grant No. 2014CB965001 to J.C.Z.), the National Institutes of Health (1R01NS097195-01 to J.C.Z.), the National Natural Science Foundation of China (No. 81901333 to X.X.), Shanghai Sailing Program (No. 19YF1451700 to X.X.), and the National Natural Science Foundation of China (No. 81870042 to P.Y.). Conflict of Interest: The authors declare no conflict of interests regarding the publication of this paper.Ethical Approval: Not applicable.