Risk of Appendicitis After mRNA COVID-19 Vaccination: A Population-based Cohort Study

Background: Appendicitis has been reported as a potential adverse event following immunization with mRNA-based vaccines against coronavirus disease 2019 (COVID-19).

Objectives: To evaluate the risk of appendicitis following mRNA vaccination against COVID-19.

Methods: Using Danish nationwide registries, we conducted a population-based cohort study of all recipients of the BNT162b2 (Comirnaty ®, Pfizer-BioNTech) and mRNA-1273 (Spikevax ®, Moderna) vaccine and all individuals with PCR-test confirmed severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection aged 12 years or more in Denmark until November 30, 2021. For comparison, we sampled an unvaccinated reference cohort among all Danish individuals aged 12 years or more tested for SARS-CoV-2. Individuals hospitalized with appendicitis or with a surgical procedure code of appendectomy were identified in the Danish National Patient Registry. Using propensity score derived standardized morbidity ratio weights, we estimated the risk ratio for the combined outcome of appendicitis or appendectomy 21 days after immunization against COVID-19 with the first or second dose, and 21 days after SARS-CoV-2 infection, adjusted for age, sex, municipality, immigration status, history of inflammatory bowel disease, diabetes, and history of antibiotic prescription fills.

Results: Among 4,048,883 individuals aged 12 years or more immunized with a mRNA vaccine against COVID-19, there were 330 episodes of appendicitis within 21 days of the first dose, and 340 episodes within 21 days of the second dose. When compared to the unvaccinated reference cohort, the adjusted risk ratio for appendicitis was 0.93 (95% confidence interval (CI), 0.79-1.11) and 0.99 (95% CI, 0.84-1.18) 21 days after the first and second dose, respectively. This null-association was stable across age groups, sex and vaccine type. The corresponding risk ratio for appendicitis 21 days following SARS-CoV-2 infection was 1.25 (95% CI, 0.79-1.99; N=20/159,115).

Conclusions: In this nationwide study, the BNT162b2 and mRNA-1273 vaccine was not associated with an excess risk of appendicitis when compared to an unvaccinated reference cohort. Likewise, we found no increased risk of appendicitis 21 days following SARS-CoV-2 infection.