Anaphylactic events in mRNA vaccines: a reporting case-control study

  1. Chris von Csefalvay

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Abstract

Background

mRNA vaccines are a novel method of eliciting immunity, and play a significant role in the global fight against COVID-19. Anaphylactic reactions are a widespread concern driving vaccine hesitancy due to the serious and potentially fatal nature of anaphylaxis. A quantitative estimation of the risk of anaphylactic and ana-phylactoid reactions deriving from mRNA vaccines is of a significant public health importance.

Objective

To estimate the relative Reporting Odds Ratio of anaphylactic and ana-phylactoid reactions following mRNA vaccination vis-a-vis other vaccinations.

Design

Reporting case-control study.

Setting

Persons reporting adverse events following vaccination to VAERS whose reports were received between 01 January 2000 and 02 July 2021, inclusive.

Patients

Each case of anaphylaxis or anaphylactoid reaction was matched with 2.7 unique controls on average, by gender and age rounded to the nearest integer.

Measurements

Overall and stratified Reporting Odds Ratios (ROR) were calculated. Stratified contingency tables were tested for homogeneity using the Breslow-Day procedure, and Cochran-Mantel-Haenszel statistics were calculated to test the hypothesis of a ROR of unity.

Results

2,665 cases of anaphylaxis or anaphylactoid reactions and 7,125 controls of non-anaphylactic/anaphylactoid reports were compared. The ROR of an anaphylactic or anaphylactoid reaction was 1.325 (95% CI: 1.212 – 1.448, p < 0.001). The matched set of cases and controls revealed an expected inhomogeneity by sex (with women slightly more likely to report anaphylactic presentations) and age band strata (with a bimodal distribution that reflects the common incidence of anaphylactic and allergic pathologies). No significant increase in the risk of anaphylactic adverse events was witnessed among persons who self-reported previous allergic reactions to vaccines. A slightly elevated ROR was observed with patients who reported a history of allergic reactions to NSAIDs and/or fluoroquinolone antibiotics. The precise meaning and relevance of this finding remains to be elucidated.

Limitations

As a reporting study using data from VAERS, our analysis is subject tunder- and overreporting, the extent of each of which is not known with any degree of precision. Since the Emergency Use Authorizations for both mRNA vaccines mandate reporting of all serious adverse events, reporting bias is likely in favour of non-mRNA vaccines, where such reporting is not mandatory in adults. Consequently, this analysis may exaggerate the ROR of anaphylactic and anaphylactoid events associated with mRNA vaccines, which may in reality be significantly lower.

Conclusions

mRNA vaccination is not associated with a statistically significant higher risk of reporting an anaphylactic adverse event to VAERS. Anaphylaxis is a serious but very rare complication of all immunisations. No significant increase in reporting odds was found in any age group or gender, nor in most cases of previously known allergic adverse events in relation to vaccines. This study contributes to the growing body of evidence proving the safety and tolerability of mRNA vaccines.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.19.21260714: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The data files from 2000 onwards were loaded and processed using Python
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    4.4 Limitations: This study relied strongly on reporting from VAERS. As all studies that utilise passive reporting data, it is limited by the biases inherent in reporting itself. These biases, by definition, are imperfectly understood.[20–22] Underreporting, in which an adverse effect is not reported, is a frequent confounder, as is overreporting, where the same event is reported multiple times, often due to an innocent lack of communication (e.g. the parent of a vaccinated child makes a report, unsure whether the physician will also make a report). To some extent, underreporting is mitigated for the mRNA-based vaccines currently approved. Both mRNA vaccines are administered under Emergency Use Authorizations that mandate reporting to VAERS of any serious adverse effects, whereas such mandatory reporting is typically only applicable for other vaccines if they fall within the scope ratione materiae of the National Childhood Vaccine Injury Act’s mandatory reporting provisions. Since anaphylaxis almost always necessitates treatment, frequently results in hospitalisation and is considered a serious, indeed life-threatening, medical emergency by providers, it is very likely that the rate of underreporting is quite low. Because non-mRNA vaccines, except for the Janssen COVID-19 vaccine, are not held to this standard, it is quite likely that there is a bias from differential underreporting. The likelihood of reporting an anaphylactic or anaphylactoid reaction to VAERS is higher for ...

    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.

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  2. Version published to 10.1101/2021.07.19.21260714 on medRxiv