# Effectiveness of the 2024–2025 KP.2 COVID-19 vaccines in the United States during long-term follow-up

## TL;DR

This study found that the 2024-2025 KP.2 COVID-19 vaccines provided strong protection against death but limited protection against infection and hospitalization, with effectiveness declining over time.

## Contribution

The study provides up-to-date, real-world evidence on the long-term effectiveness of the KP.2-targeting vaccines in a large, older adult population.

## Key findings

- VE against SARS-CoV-2-associated death was high at 65.53%.
- VE against infection, ED/UC visits, and hospitalization was modest and declined over time.
- Effectiveness dropped significantly from 60 to 120 days post-vaccination.

## Abstract

Up-to-date estimates of COVID-19 vaccine effectiveness (VE) are needed to inform COVID-19 vaccination strategies and recommendations. This target trial emulation study aimed to estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration. The study population (90.9% male, mean age 70.7 years) included 538,631 pairs of vaccinated (i.e., received the KP.2 COVID-19 vaccine) and matched unvaccinated (i.e., did not receive the KP.2 COVID-19 vaccine) persons enrolled from August 2024 to January 2025. Over a mean follow-up of 172 days (range 97-232) extending to April 12, 2025, VE was low against laboratory-diagnosed SARS-CoV-2 infection (16.60%, 95% confidence interval [CI], 11.92-21.44), SARS-CoV-2-associated emergency department/urgent care (ED/UC) visit (21.05%, 95% CI, 14.22-27.21), SARS-CoV-2-associated hospitalization (19.53%, 95% CI 6.56-30.10) and much higher against SARS-CoV-2-associated death (65.53%, 95% CI 27.79-83.37). VE declined from 60 to 90 to 120 days against infection (31.28%, 25.81%, 22.44% respectively), ED/UC visit (34.40%, 29.19%, 25.71% respectively), hospitalization (37.39%, 28.98%, 22.52% respectively) and death (75.02%, 71.02%, 63.08% respectively). In conclusion, COVID-19 vaccines targeting the KP.2 variant used in the 2024-2025 season offered high protection against death and modest protection against infection, ED/UC visits or hospitalization, and VE declined over time.

Vaccinations against the SARS-CoV-2 KP.2 variant were introduced for the 2024-25 season in the United States. Here, the authors investigate the effectiveness of these vaccines up to April 2025 through a target trial emulation study using electronic health record data.