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

  1. Ping Yuan
  2. Pu Ai
  3. Yihan Liu
  4. Zisheng Ai
  5. Yi Wang
  6. Weijun Cao
  7. Xiaohuan Xia
  8. Jialin C. Zheng

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Abstract

We aimed 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 coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% CI : 1.90-4.29) or high ( CI : 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 ( P = 0.0004 and P = 0.0003, respectively) and day 28/35 ( P < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All P < 0.001). In conclusion, 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.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.03.20224998: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationStudy selection: We included randomized, double-blind, placebo-controlled studies.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Study inclusion criteria were: healthy adults (18 years and older) without history of SARS-CoV (via on-site inquiry) or SARS-CoV-2 infection (via serological and nucleic acid test); Before vaccination or placebo and at days 14, 21, 28 or 35 after injections, subjects were asked to record any injection local adverse reactions (e.g. pain, itching, redness, swelling and induration) and systemic adverse reactions (e.g. coughing, diarrhea, fatigue, fever and headache), and subjects received routine laboratory blood tests and antibody tests included the neutralizing antibody and the specific IgG-binding antibody titers.
    specific IgG-binding
    suggested: None
    Similarly, immunogenicity outcomes were evaluated by abnormal hemoglobin, alanine aminotransferase and total bilirubin, IgG or other specific antibody responses to the receptor binding domain, and neutralizing antibodies to live SARS-CoV-2.
    total bilirubin, IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    We searched systematically in PubMed, Embase, the Cochrane Library, and medRxiv using the key words “COVID-19” or “SARS-CoV-2” and “vaccination” or “vaccine” to identify all published and pre-publication studies from the database inception to October 20, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Risk of bias was assessed for the domains suggested by the Cochrane Handbook of Systematic Reviews [11], specifically emphasizing sequence generation, allocation concealment, blinding, outcomes assessment, and selective reporting for the 5 included trials.
    Cochrane Handbook of Systematic Reviews
    suggested: None
    Analyses were performed using the Cochrane Collaboration Review Manager (version 5.2, Cochrane Collaboration, Copenhagen, Denmark).
    Cochrane Collaboration Review Manager
    suggested: None
    Cochrane Collaboration
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, this review has several limitations. In summary, our study is the first meta-analysis summarizing the current progress in the SARS-CoV-2 vaccine development. The results from our analysis implicate excellent safety, tolerability, and immunogenicity of all included COVID-19 vaccine candidates, providing great confidence for the following development and clinical application of COVID-19 vaccines. Therefore, our study suggests that, although there are limitations in current studies such as the short follow-up time and small sizes of subjects, with the conduction of large-scale clinical efficacy trials, the successful development of safe, effective, durable, and deployable to large populations COVID-19 vaccines to end the global SARS-CoV-2 pandemic will be a near possibility.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.11.03.20224998v1 on medRxiv