ANALYSIS of over 1.5 million U.S. adults in a new study has found that annual COVID-19 variant-targeted boosters provide meaningful protection against severe disease but lose effectiveness beyond 6 months. The research, which followed a large cohort of vaccinated individuals, underscores the short-term benefits of booster doses while raising questions about long-term protection.
The study examined the impact of mRNA variant-targeted boosters on preventing hospitalization and severe illness due to COVID-19 pneumonia. The cohort included U.S. veterans who had previously received booster doses, with a subset receiving the updated variant-targeted booster starting in September 2022. Researchers matched individuals who did and did not receive the updated booster and tracked their health outcomes through August 2023.
The results showed that individuals with vaccine-derived immunity experienced a 29% relative reduction in hospitalization risk due to COVID-19 pneumonia after receiving the booster. Those with hybrid immunity, prior infection plus vaccination, saw a slightly higher 38% reduction in hospitalization risk. However, these protective effects were only significant in the first 6 months after vaccination and did not persist beyond that period. The pattern remained consistent across both the pre-XBB and XBB variant waves.
These findings highlight the ongoing challenge of maintaining durable immunity against COVID-19. While annual boosters still provide a meaningful short-term reduction in severe cases, their waning effectiveness over time may prompt discussions on whether more frequent booster recommendations or alternative vaccine strategies are needed, particularly for high-risk populations.
For healthcare providers, this study reinforces the importance of ensuring high-risk patients receive their annual booster doses promptly, especially before seasonal surges. As COVID-19 continues to evolve, future vaccine strategies may need to address declining immunity to sustain long-term protection.
Reference: Daniel Kelly J et al. Annual variant-targeted vaccination to prevent severe COVID-19 disease in cohorts with vaccine-derived and hybrid immunity. Clin Infect Dis. 2025;ciaf124.
Anaya Malik | AMJ
