Long-term safety of the Pfizer-BioNTech COVID-19 vaccine: Results from the HERO-together study

BACKGROUND: COVID-19 vaccines were initially authorized based on short-term data from Phase 3 clinical trials in a highly selected population. OBJECTIVES: This study assessed the long-term safety of the Pfizer-BioNTech COVID-19 vaccine BNT162b2 and variation in adverse event rates across clinically important subgroups. METHODS: This 24-month prospective safety surveillance study was conducted using a participant-facing portal with centralized event adjudication. Participants included 19,858 adults receiving a COVID-19 vaccine in the US from any manufacturer in the 60 days before enrollment. The main outcome measures were adverse events of special interest (AESIs) and all-cause hospitalizations, with event rate ratios evaluated using the self-controlled risk interval method. RESULTS: Of the 9518 participants (median age 36.6 years) in the primary safety population (vaccinated with BNT162b2 within 10 days of enrollment), most were female (69.0%), White (66.1%), and non-Hispanic (75.2%). The most frequent baseline health conditions were obesity/overweight (24.4%), hypertension (11.9%), and asthma (11.6%). The overall AESI rate was 13.65 per 1000 person-years. Most AESIs did not result in hospitalization (67.4%). The most common AESIs per 1000 person-years were arthritis/arthralgia (3.32), non-anaphylactic allergic reactions (2.84), and spontaneous abortion/stillbirth (3.10). The rate of all other AESIs was <1.0 per 1000 person-years. Unadjusted AESI rates (IRR; 95% CI) were higher in risk intervals than control intervals (2.32; 1.54-3.51) but were attenuated following adjustment for age (0.95; 0.53-1.72). CONCLUSIONS: AESI risk was low; the most common AESIs were arthritis/arthralgia and non-severe allergic reactions, with no increased incidence of a composite AESI or all-cause hospitalization post-vaccination. BNT162b2 has a favorable long-term safety profile in real-world settings.