Risk-based prediction for optimal timing of booster vaccination for COVID-19 to prevent severe disease

There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.