OBJECTIVES: Historical incidence rates (IRs) for Adverse Events of Special Interest (AESIs) are important for vaccine impact assessment and safety monitoring. A source covering a comprehensive list of AESIs from the general population is needed to provide representative historical IRs of AESIs, as well as quantify the impact of the COVID-19 pandemic on the IRs of AESIs.

METHODS: The IRs of 43 AESIs were assessed in a cohort study of the US general population using patient-level claims data aggregated by HealthVerity for the pre-COVID period (01 January 2019 – 29 February 2020) and active-COVID period before vaccines were available (01 March 2020 – 30 November 2020). The IRs per 100,000 person-years were calculated among individuals without a diagnosis of the applicable AESI during the AESI-specific washout period (up to one-year before cohort entry). The age- and sex-specific IRs were also assessed in the pre-COVID and active-COVID periods.

RESULTS: A total of 21.3 and 19.6 million individuals were included in the pre-COVID and active-COVID periods. Demographic characteristics were similar for the pre-COVID and active-COVID populations (with the same median ages [43 years] and sex distribution [47% for males], and similar insurance coverage patterns). IRs of all AESIs increased substantially with age, except for anaphylaxis, appendicitis, and Kawasaki disease, where IRs decreased with advancing age. Females had lower IRs in 13 AESIs and higher IRs in 14 AESIs compared to males by > 15%.

Compared to the pre-COVID period, IRs of 22 (51%) AESIs decreased by > 15% in the active-COVID period (capillary leak syndrome had the highest decrease by 61.54%), and IRs for 4 AESIs increased by >15% (cardiac arrest had the highest increase by 142.57%).

CONCLUSIONS: This study assessed the largest number of AESIs to date, providing reliable IRs from a representative population of the US for disease burden assessment and safety surveillance.