Data on effectiveness of 2024–2025 COVID-19 vaccines remain limited. This study estimated real-world effectiveness of the 2024–2025 formulation BNT162b2 (KP.2) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits over the 2024–2025 respiratory virus season. The analysis focused on non-immunocompromised adults living in two US states and aimed to evaluate protection overall and within clinically relevant subgroups.
Investigators conducted a retrospective cohort study using vaccine registries linked to administrative claims in the HealthVerity database. Eligible participants were non-immunocompromised adults residing in California or Louisiana with at least one year of continuous insurance enrollment beginning 22 August 2024. The analytic cohort comprised 6,256,421 individuals, of whom 330,565 (5%) received the KP.2 formulation of BNT162b2 during the observation period.
Vaccination status with BNT162b2 KP.2 was modeled as a time-varying exposure. COVID-19-associated encounters were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1. Outcomes included hospital admissions, ED visits, and UC visits attributed to COVID-19; analyses considered each outcome separately and in combination.
Effectiveness was estimated as 1 minus the adjusted hazard ratio derived from Cox proportional hazards models. Models adjusted for age group, sex, state (California or Louisiana), insurance payer, presence or absence of underlying medical conditions (UMCs), and pre-index healthcare utilization. Stratified analyses were prespecified for adults aged 65 years and older, adults aged 18–64 years with UMCs, and adults aged 18–64 years without UMCs.
Of the full cohort, 93% resided in California and 7% in Louisiana. Vaccinated individuals were described as older and having higher prevalence of comorbidities, more wellness visits, and greater uptake of prior influenza vaccination compared with unvaccinated individuals. Overall, 66% of study participants had at least one UMC. The most prevalent UMCs reported in the abstract were obesity (25%), a history of immunocompromising conditions (23%; note that the cohort was described as non-immunocompromised—this likely refers to history documented in claims), and mental health conditions (19%).
Observed COVID-19-related encounter rates (ED, UC, or hospitalization) were lower among vaccinated versus unvaccinated participants: 25.1 versus 36.3 per 100,000 person-months. In adjusted analyses across all adults, vaccine effectiveness was reported as:
These estimates represent VE for the KP.2 BNT162b2 formulation over the course of the 2024–2025 respiratory virus season as measured in this claims- and registry-linked cohort.
Stratified results were reported as similar across the examined groups: adults aged 65 years and older; adults aged 18–64 years with UMCs; and adults aged 18–64 years without UMCs. The abstract reports no meaningful divergence in VE estimates by these stratifications, indicating consistent direction of protection across age and comorbidity categories.
In this large retrospective cohort of non-immunocompromised adults in two US states, receipt of the 2024–2025 BNT162b2 KP.2 vaccine was associated with reduced rates of COVID-19-associated ED, UC, and hospitalization encounters. The authors conclude that KP.2 provided measurable protection during the 2024–2025 respiratory season, including among adults with underlying medical conditions, and state that these findings support continued vaccine recommendations.
The study was posted on ClinicalTrials.gov prior to analyses (NCT06923137). The abstract provides key design elements, cohort size, outcome definitions, incidence rates, and adjusted VE estimates. Details not reported in the abstract include exact follow-up duration, calendar time windows for outcomes, variant-specific circulation during the study period, absolute numbers of outcome events for each group, confidence intervals or measures of statistical precision for VE estimates, and results of any sensitivity analyses; those details would need to be obtained from the full text.