Post-emergency use authorization active safety surveillance study of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine in the Veterans Affairs health system: Findings from a three-year, comprehensive safety assessment program

This non-interventional, active safety surveillance study conducted signal detection/evaluation analyses for the primary series, monovalent booster doses, and Omicron BA.4/BA.5-adapted bivalent booster dose of the Pfizer-BioNTech COVID-19 vaccine among Veterans Health Administration (VHA) enrollees. Repeated longitudinal, cohort study analyses using data from the VHA Corporate Data Warehouse were conducted. Among individuals who received ≥1 Pfizer-BioNTech COVID-19 vaccination between 12/11/2020–06/30/2023, an active comparator design was used to monitor the occurrence of 48 safety events of interest in this population compared to individuals with seasonal influenza vaccines during the 2014/2015–2018/2019 influenza seasons. In addition, a self-controlled risk interval design was used to compare the occurrence of safety events of interest during post-vaccination risk versus control intervals among individuals experiencing the safety event of interest. The Pfizer-BioNTech COVID-19 vaccine sample comprised 1,652,514 individuals, the majority of whom were male (89.8%) with an average age of 64.0 years (median = 67.4); it included 59.7% White non-Hispanic and 22.0% Black individuals. The seasonal influenza vaccine sample included 4,104,220 individuals, and baseline demographic and clinical characteristics were generally similar between the Pfizer-BioNTech COVID-19 and seasonal influenza vaccine samples (standardized differences<10%). After signal detection analyses, further investigation was warranted for cerebrovascular non hemorrhagic stroke, other acute demyelinating disease, Guillain-Barré syndrome, anaphylaxis, acute myocardial infarction, arrhythmia, coronary artery disease, myocarditis, stress cardiomyopathy, microangiopathy, chilblain-like lesions, hemorrhagic disease, pulmonary embolism, optic neuritis, heart failure and cardiogenic shock, acute kidney injury, deep vein thrombosis, and severe COVID-19 disease. However, no safety events remained after signal evaluation analysis (including for myocarditis/pericarditis), regardless of the vaccine dose. There was no increased risk of any of the 48 safety events of interest evaluated following Pfizer-BioNTech COVID-19 vaccination in the VHA population.