Background: Over 86% of older adults aged [≥]65 years are fully vaccinated against SARS-COV-2 in the United States (US). Waning protection of the existing vaccines promotes the new vaccination strategies, such as providing a booster shot for those fully vaccinated. Methods: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of Pfizer-BioNTech BNT162b2 (administered 6 months after 2nd dose) in those aged [≥]65 years, from a healthcare system perspective. Findings: Compared with 2-doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million, but save $6.7 million in direct medical costs in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that with a COVID-19 incidence of 9.1/100,000 person-day, a booster strategy has a high chance (67%) of being cost-effective. The cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. This threshold will increase with a decrease in vaccine and booster efficacies. Doubling the vaccination cost or halving the medical cost for COVID-19 treatment alone would not alter the conclusion of cost-effectiveness, but certain combinations of the two might render the booster strategy not cost-effective. Interpretation: Offering BNT162b2 boosters to older adults aged [≥]65 years in the US is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-COV-2 transmission. Funding: National Natural Science Foundation of China. Berlina and Bill Gates Foundation
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