BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults

ImportanceData describing the early additional protection afforded by recently recommended XBB1.5- adapted COVID-19 vaccines are limited. ObjectiveWe estimated the association between receipt of BNT162b2 XBB1.5-adapted vaccine (Pfizer- BioNTech 2023-2024 formulation) and medically attended COVID-19 outcomes among adults [≥]18 years of age. Design, Setting, and ParticipantsWe performed a test-negative case-control study to compare the odds of BNT162b2 XBB1.5- adapted vaccine receipt between COVID-19 cases and test-negative controls among adults in the Kaiser Permanente Southern California health system between October 11 and December 10, 2023. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. ExposureThe primary exposure was receipt of BNT162b2 XBB1.5-adapted vaccine compared to not receiving an XBB1.5-adapted vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. We also compared receipt of prior (non-XBB1.5-adapted) versions of COVID-19 vaccines to the unvaccinated to estimate remaining protection from older vaccines. Main Outcomes and MeasuresCases were those with a positive SARS-CoV-2 polymerase chain reaction test, and controls tested negative. Analyses were done separately for COVID-19 hospital admissions, emergency department (ED) and urgent care (UC) encounters, and outpatient visits. ResultsAmong 4232 cases and 19,775 controls with median age of 54 years, adjusted ORs for testing positive for SARS-CoV-2 among those who received BNT162b2 XBB1.5-adapted vaccine a median of 30 days ago (vs not having received an XBB1.5-adapted vaccine of any kind) were 0.37 (95% CI: 0.20-0.67) for COVID-19 hospitalization, 0.42 (0.34-0.53) for ED/UC visits, and 0.42 (0.27-0.66) for outpatient visits. Compared to the unvaccinated, those who had received only older versions of COVID-19 vaccines did not show significantly reduced risk of COVID-19 outcomes, including hospital admission. Conclusions and RelevanceOur findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) XBB1.5-adapted vaccines provided significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, additional protection, including against hospital admission, regardless of the number or type of prior doses received. KEY POINTS QuestionsDoes receiving the BNT162b2 XBB1.5-adapted vaccine offer additional protection against COVID-19 hospital admission and ambulatory visits in US adults [≥]18 years of age compared to not receiving an XBB1.5-adapted vaccine of any kind? Do older versions of COVID-19 vaccine still provide any protection compared to the unvaccinated? FindingsThe BNT162b2 XBB1.5-adapted vaccine (Pfizer-BioNTech 2023-2024 formulation) provided significant additional protection against a range of COVID-19 outcomes during a period when XBB sub-lineages were predominant but JN.1 was also co-circulating and rapidly increasing in prevalence. Older versions of COVID-19 vaccines offered little, if any, additional protection compared to the unvaccinated, including against COVID-19 hospital admission, regardless of the number or type of prior doses received. MeaningOur findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines.