Early effectiveness of the BNT162b2 KP.2 vaccine against COVID-19 in the US Veterans Affairs Healthcare System

This test-negative case-control study within the US Veterans Affairs Healthcare System aims to estimate early vaccine effectiveness (VE) of the BNT162b2 KP.2 vaccine (2024-2025 formulation) compared to not receiving the KP.2 vaccine against COVID-19 outcomes. The study includes adult patients (age ≥18 years) with an acute respiratory infection (ARI) in hospital, emergency department and urgent care (ED/UC), or outpatient settings between September 5 and November 30, 2024. Separate multivariable logistic regression models compare the odds of receiving BNT162b2 KP.2 vaccine among SARS-CoV-2 positive cases and test-negative controls within each ARI outcome category, while adjusting for potentially confounding variables. Among 44,598 ARI episodes, VE is 68% (42-82%), 57% (46-65%), and 56% (36-69%) against COVID-19-associated hospitalizations, emergency department and urgent care visits, and outpatient visits, respectively. Uptake of updated COVID-19 vaccines is low (3.7%).