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

Importance Data describing the early additional protection afforded by recently recommended XBB1.5-adapted COVID-19 vaccines are limited. Objective We 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 Participants We 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. Exposure The 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 Measures Cases 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. Results Among 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 Relevance Our 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.