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. Questions Does 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? Findings The 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. Meaning Our findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines. ### Competing Interest Statement LJ, LP, and JMM are employees of and hold stock and/or stock options in Pfizer Inc. SYT, TF, JMS, VH, SS, JAS and BA received research support from Pfizer during the conduct of this study that was paid directly to KPSC. BA received research support for work unrelated to this study provided by Pfizer, Moderna, Dynavax, Seqirus, GlaxoSmithKline and Genentech. JMS received research support from ALK, Inc., Dynavax, and Novavax for work unrelated to this study. TBF previously owned stock in Pfizer Inc. SYT received research support from GSK and Genentech for work unrelated to this study. ### Funding Statement This study was sponsored by Pfizer. The study design was jointly developed by KPSC and Pfizer. KPSC collected and analyzed the data. Pfizer did not participate in the collection or analysis of data. KPSC and Pfizer participated in the interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Kaiser Permanente Southern California Institutional Review Board which waived the requirement for informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymized data that support the findings of this study may be made available from the investigative team in the following conditions: (1) agreement to collaborate with the study team on all publications, (2) provision of external funding for administrative and investigator time necessary for this collaboration, (3) demonstration that the external investigative team is qualified and has documented evidence of training for human subjects protections, and (4) agreement to abide by the terms outlined in data use agreements between institutions.