Publication date: Jul 11, 2023

While waning protection from vaccination and natural infection against SARS-CoV-2 infection is well-documented, recent analyses have also found waning of protection against severe COVID-19. This highlights a broader need to understand the optimal timing of COVID-19 booster vaccines specific to an individual to mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age group and immune status. Here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively mitigate the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit. Analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, we estimated that in persons 75+ years, annual and semiannual bivalent boosters would reduce annual absolute risk of severe COVID-19 by 311 (277-369) and 578 (494-671) cases, respectively, compared to a one-time bivalent booster dose. In contrast, for persons 18-49 years, the model estimated that annual and semiannual bivalent boosters would reduce annual absolute risk of severe COVID-19 by 20 (13-26) and 37 (24-50) cases per 100,000 persons, respectively, compared to a one-time bivalent booster dose. Persons with prior infection had a much lower benefit of more frequent boosting, while immunocompromised persons had larger benefit. This study underscores the benefit of customizing timing of COVID-19 booster vaccines based on individual risk.

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