An objective systematic comparison of the most common adverse events of COVID-19 vaccines

  1. C. Behrens
  2. T. Gasperazzo
  3. M. Samii-Moghadam
  4. J.B. Lampe

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Abstract

Background

Vaccination is an important tool in the fight against pandemics. However, the associated adverse events (AEs) may negatively impact the public perception of vaccines, therefore leading to decreased vaccination willingness. Interestingly, pharmacovigilance data of the three COVID-19 vaccines with a two-dose schedule approved in the EU (AstraZeneca, BioNTech and Moderna) already revealed country-specific differences in their safety profile early on (as of February 2021), at a time when the accumulated occurrence of specific AEs was not yet known. In the safety outcome assessment presented here, we aimed to establish whether these country-specific differences in pharmacovigilance data could be explained by differences in the frequency of AEs as reported in the respective approval studies of each vaccine.

Methods

A systematic search was performed to identify all publications regarding the randomized controlled trials (RCTs) of two-dose vaccines approved in the EU (AstraZeneca, BioNTech and Moderna), including regulatory reports and journal articles. All obtained safety data was manually entered into an SQL database. In order to enable the comparability among the data, the solicited AEs for all vaccines (i.e. those AEs actively sought after vaccination) were investigated. The data was standardized to promote comparability and overcome data heterogeneity and complexity.

Findings

Twelve documents regarding the RCTs for the three COVID-19 vaccines with a two-dose schedule approved in the EU (AstraZeneca, BioNTech and Moderna) were included in the safety outcome analysis. The entire safety data compiled in the SQL database amounted to 66 different study arms. The data structure revealed 13 different age thresholds or ranges and three different data sets regarding doses (first dose vs. second dose vs. all doses). After standardization and identification of subgroups, the analyses demonstrated that the highest rates of AEs occur after the first dose with the AstraZeneca vaccine, whereas with Moderna and BioNTech most AEs occur after the second dose. Astonishingly, the absolute frequencies of each AE after the first AstraZeneca dose correspond to those of the second dose of the mRNA vaccines (BioNTech and Moderna). Reversely, the absolute frequencies of the same AEs after the second AstraZeneca dose correspond to those of the first dose with the mRNA vaccines. The most common AEs with any vaccine were fatigue, headache and myalgia. Moreover, middle-aged subjects (18 to 55 years) had more side effects than older individuals (> 55 years), an observation that persisted among vaccines.

Interpretation

This is the first indirect comparison of these vaccines that uses all available RCT data. The absolute frequency of each AE is similar between the first AstraZeneca dose and the second dose of BioNTech or Moderna; their occurrence was thus independent of platform (vector or mRNA) or the vaccine itself. This assessment demonstrates that the varying frequencies of AEs reported in early pharmacovigilance data for the vaccines in distinct countries, at a time when the accumulated occurrence of specific AEs with certain vaccines was not yet known, cannot be explained by different frequencies being reported in the respective RCTs.

Conclusion

The approach presented here could help to objectify future discussions on vaccine preferences. Therefore, it may serve as basis for future public awareness campaigns and may also allow the comparison of vaccine performance in different subgroups (e.g. virus variants, high-risk patients). This approach may also be applied to a broad range of other challenges across the R&D process and various disease categories.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.11.21264830: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A systematic search was performed to identify journal articles and regulatory documents regarding the RCTs of the COVID-19 vaccines with a two-dose schedule approved in the EU: the mRNA vaccines BNT162b2 (Comirnaty) by BioNTech/Pfizer and mRNA-1273 (Spikevax) by Moderna; and AZD1222/ChAdOx1 (Vaxzevria), developed by AstraZeneca/Oxford University.
    BioNTech/Pfizer
    suggested: None
    The data was analyzed and visualized with the software Spotfire (version 10.10.0).
    Spotfire
    suggested: (Spotfire, RRID:SCR_008858)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.10.11.21264830 on medRxiv