Rethinking seasonal COVID-19 vaccination in the endemic era: summer timing, eligibility, and frequency in the United States

Importance: With a recent shift towards summer seasonal predominance of COVID-19 across much of the US, debate continues over optimal COVID-19 vaccination strategies regarding timing (including summer vaccination), eligibility, and dosing frequency. We evaluated the population-level impact of alternative vaccine strategies to inform US and state vaccine policy. Objective: To compare reductions in COVID-19 hospitalizations under different vaccination timing, eligibility, and dosing frequency. Design: Decision analytical model using a stochastic individual-based model of SARS-CoV-2 transmission, calibrated to US COVID-19 hospitalization incidence from May 2024-April 2025. Setting: Simulated US national population, with additional scenarios representing state-level seasonal patterns. Participants: Simulated population of 5 million individuals with US age structure, stratified by risk group (immunocompetent, high risk with comorbid conditions, or immunocompromised). Exposures: Vaccination timing, universal or age- and risk-based eligibility, and dosing frequency, including a hybrid strategy of universal annual vaccination with a second dose for adults [≥]65 years and immunocompromised adults (US vaccine policy during the study period). Main Outcomes and Measures: COVID-19 hospitalization risk per 100,000 persons by age-risk group, measured among vaccinated individuals and in the total population. Results: If summer COVID-19 vaccination timing is feasible, annual universal vaccination in July minimized risk (441 [95% UI: 423-463] COVID-19 hospitalizations per 100,000 persons among adults [≥]65 years) compared to a counterfactual scenario with no additional vaccination given during the study period (578 [553-601]). If timing does not change, hybrid vaccination minimized risk, followed by semiannual risk-based vaccination (460 [440-487] and 477 [454-499] hospitalizations per 100,000 in adults [≥]65 years, respectively). The advantage of summer timing diminished if vaccine coverage decreased by 5-10 absolute percentage points (25-50% relative decrease). The magnitude of benefit from summer-timed vaccination and semiannual doses in the highest-risk groups varied regionally. Conclusions and Relevance: Although annual COVID-19 vaccination has historically been timed for winter transmission, summer vaccination may avert more hospitalizations if coverage is maintained, especially in states with predominantly summer transmission including Western and Southern states. The comparative impact of vaccination strategies, especially the benefit of a semiannual dose in the highest-risk groups, may vary regionally. COVID-19 vaccination timing and eligibility may warrant reconsideration.