Understanding the effectiveness of the Comirnaty monovalent and bivalent vaccines during the Winter Coronavirus (COVID-19) Infection Study

Background: Understanding the effectiveness of SARS-CoV-2 vaccines over time is critical for informing booster strategies, vaccine types, and public health policies, particularly with the continued emergence of novel SARS-CoV-2 variants. Methods: The Winter Coronavirus (COVID-19) Infection Study (WCIS), conducted from November 2023 to March 2024, involved approximately 150,000 participants aged 3 years and older from England and Scotland. The WCIS tested participants at regular intervals for SARS-CoV-2 using lateral flow tests to estimate prevalence and incidence in near real-time. Survival analysis using Cox proportional hazards regression was conducted, using WCIS data linked to participant vaccination records, to evaluate the association between time since vaccination and the risk of SARS-CoV-2 infection and symptomatic infection. Vaccine effectiveness (VE) was evaluated for the Comirnaty Omicron XBB.1.5 and Comirnaty Omicron BA.5 vaccines for those aged 65 years old and over. The model incorporated time-varying covariates within the counting process framework, stratified baseline hazards by age group, region, and time, and included key covariates such as sex, clinical risk status, ethnicity, and socioeconomic indicators. VE was estimated from hazard ratios, and penalised cubic splines were used to capture the nonlinear effects of time since vaccination. Results: We estimated that the VE for the Comirnaty Omicron XBB.1.5 vaccine peaked at day 14 post-vaccination, reaching 70.63% (95% Confidence Intervals (CI): 43.33%, 84.78%) against infection and 63.62% (95% CI: 22.69%, 82.88%) against symptomatic infection. VE declined rapidly and by approximately weeks 9–12 post vaccination, the VE point estimates were close to zero with considerable uncertainty in the estimates from day 60 onwards. In contrast, the Comirnaty Omicron BA.5 bivalent vaccine showed little evidence of effectiveness within the study period, with VE estimates close to zero and wide confidence intervals crossing zero. Conclusions: These findings provide important insights into the effectiveness of targeted vaccine strategies in the context of an evolving pandemic. As SARS-CoV-2 continues to mutate, adaptive approaches in vaccine design and public health policy will be key to addressing emerging variants and protecting high-risk groups.