Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Background: Despite the importance of the COVID-19 vaccine, little is known about the effectiveness and side effects on available vaccines. The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in phase I, II and III randomized clinical trials (RCT) to provide a better estimate of their efficacy, side effects and immunogenicity. Methods: All relevant publications were systematically searched and collected from major databases up to 12 March 2021. The total vaccine’s efficacy, sub-group antigen-specific efficacy, odds ratios (ORs) for side effects, and sub-group OR based on adjuvants for each vaccine pooled by random-effects model. Findings: A total of 25 RCTs (123 datasets), 58889 cases that received the COVID-19 vaccine and 46638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.96.4-0.92.7) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first 97.6% (95% CI 0.939-0.997) and second 98.2% (95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for the diarrhea and arthralgia that displayed the highest OR for the adenovirus-vectored vaccine. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines’ adjuvant or without adjuvant, except for the injection site redness. Interpretation: The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. None experienced adverse effects and all stimulated robust immune responses. All RCTs followed up the vaccine and placebo groups after one month after both first and second doses, therefore all reports are related to short-term impacts. Due to the timeline, all the vaccines are missing longer-term assessments. Funding Statement: The author(s) received no specific funding for this work. Declaration of Interests: The authors declare no competing interests.