Early effectiveness of the BNT162b2 LP.8.1 vaccine against COVID-19 emergency department, urgent care, and outpatient visits in the US Veterans Affairs Healthcare System

ABSTRACT This study estimated early vaccine effectiveness (VE) of the BNT162b2 LP.8.1-adapted vaccine against emergency department/urgent care (ED/UC) and outpatient visits using a test-negative case-control design. Patients from the US Veterans Affairs Healthcare System with an acute respiratory infection (ARI) who underwent SARS-CoV-2 testing from September 10 – November 30, 2025 were included. VE was estimated using multivariable logistic regression adjusted for patient demographics and clinical characteristics. Among 34,455 ARI episodes, 10.7% were COVID-19 cases and 2.4% were vaccinated. BNT162b2 LP.8.1 vaccine was effective during the early 2025–2026 respiratory virus season. VE was 57% (95% confidence interval [CI] 39%–70%) against ED/UC visits and 54% (95% CI 15%–75%) against outpatient visits at approximately 4 weeks post-vaccination. These findings inform shared decision-making in clinical practice and support the continued importance of COVID-19 vaccination in populations for whom it is recommended.