Risk of adverse events after Omicron XBB-adapted BNT162b2 COVID-19 vaccination in the United States

Limited data exists regarding the safety of the COVID-19 2023-2024 vaccine formulations and whether the safety profiles differ from the original formulations. We evaluated the association between the BNT162b2 XBB COVID-19 vaccine and the risk of 20 pre-specified adverse events of special interest (AESIs).

We identified commercially-insured individuals in the US age ≥ 6 months who received the BNT162b2 XBB COVID-19 vaccine between September 11, 2023 and January 15, 2024 within the Optum pre-adjudicated database. The self-controlled risk interval design was used to compare the incidence of 20 pre-specified AESIs during a risk period following vaccination to a control period. Relative incidence and 95 % confidence intervals (CI) were estimated using exact conditional Poisson regression.

The analysis included 113,459 individuals who received the BNT162b2 XBB COVID-19 vaccine (median [interquartile range] age: 47.1 [33.0-59.1] years). Relative incidence was calculated when ≥1 event occurred in either the risk or control period. For these 10 AESIs, there was no significant association between receipt of the BNT162b2 XBB COVID-19 vaccine and the incidence of any of these AESIs. Point estimates were higher in the risk period compared to the control period for ischemic stroke (relative incidence: 1.52; 95 % CI: 0.44-5.94), myocarditis/pericarditis (relative incidence: 1.50; 95 % CI: 0.22-12.61), immune-mediated myositis (relative incidence: 1.44; 95 % CI: 0.83-2.52), herpes zoster (relative incidence: 1.24; 95 % CI: 0.69-2.28), and non-febrile convulsions/seizures (relative incidence: 1.22; 95 % CI: 0.86-1.73). These estimates were not statistically significant, though most were based on few events. Results were generally similar in subgroup analyses of individuals administered a concomitant seasonal influenza vaccine.

There was no increased risk of 20 pre-specified AESIs following receipt of the BNT162b2 XBB COVID-19 vaccine among US commercially insured individuals aged ≥6 months. Findings are consistent with the current evidence on the safety of BNT162b2 COVID-19 vaccines. Public registration: EUPAS108135.