To determine the effectiveness of booster vaccinations on the risk of hospitalization with COVID-19, and how it varies by enrollee characteristics and interval from the initial vaccination to receipt of booster.

This cohort study used 100% Medicare claims from January 2020 through December 2021 and matched 3,940,475 individuals who received boosters to 3,940,475 controls based on week and type of original COVID-19 vaccine, and demographic and clinical characteristics. We compared the association of booster vs. no booster with COVID-19 hospitalization using Cox proportional hazards regression models controlling for patient characteristics. We also determined the association of time from original vaccine to booster with COVID-19 hospitalization.

Over a maximum of 130 days of follow-up, boosted enrollees had 8.20 (95% CI, 7.81-8.60) COVID-19 hospitalizations per million days vs. 43.70 (42.79-44.64) for controls, 81% effectiveness. Effectiveness varied by race, prior hospitalizations, and certain comorbidities; for example, leukemia/lymphoma (53% effectiveness), autoimmune disease (73%) and dementia (73%). Boosters received between 6 and 9 months after original vaccination varied between 81% and 85% effectiveness, while boosters received at 5-6 months (62%) or <5 months (58%) were less effective.

Boosters are highly effective in the Medicare population. Approximately 69,225 hospitalizations would be prevented by boosters in the 15,000,000 individuals aged 65+ currently not boosted, in a period similar to the September 2020 through January 2021 period studied. Boosters provided the greatest benefits if they were received between six to nine months following original vaccinations. However, boosters were associated with substantial decreases in COVID-19 hospitalizations in all categories of enrollees.