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

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 anaphylactoid reactions deriving from mRNA vaccines is of a significant public health importance. Objective: To estimate the relative Reporting Odds Ratio of anaphylactic and anaphylactoid 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 did not reveal inhomogeneity by gender or age band strata, suggesting that these factors have no impact on the likelihood to report an anaphylactic event as opposed to a non-anaphylactic event following mRNA vaccination. 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. Previous reactions to vaccines do not appear to correlate statistically significantly with a higher risk of reporting an anaphylactic adverse effect after mRNA vaccination. Limitations: As a reporting study using data from VAERS, our analysis is subject to under- 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.