Estimated Effectiveness of 2024-2025 COVID-19 Vaccines in Adults
The 2024-2025 COVID-19 vaccines provided modest, waning protection against medically attended illness.
*Test-negative case-control study; Level 4 (OCEBM).
Citation
Wiegand RE, Payne AB, Mak J, et al. Estimated Effectiveness of 2024-2025 COVID-19 Vaccines in Adults. JAMA Internal Medicine. 2026;186(8):976-986. doi:10.1001/jamainternmed.2026.1936
Background
Updated COVID-19 vaccines are reformulated as the virus changes. Real-world estimates are needed because most adults already have some immunity from past infection, vaccination, or both.
Patients
Adults 18 years or older in 6 US states with a COVID-like illness visit and a COVID-19 test. Exclusions included very recent vaccination, vaccination more than 299 days earlier, nonapproved vaccines, invalid dosing patterns, and some influenza or respiratory virus positive tests among controls.
Intervention
Receipt of a 2024-2025 COVID-19 vaccine 7 to 299 days before the encounter.
Control
No 2024-2025 COVID-19 vaccine dose, regardless of earlier COVID-19 vaccination history.
Outcome
COVID-19–associated emergency or urgent care visits, hospitalizations, and critical illness, defined as hospitalization with intensive care admission or in-hospital death.
Follow-up Period
7 to 299 days after vaccination.
Results
| Outcome | Population | Estimated protection |
|---|---|---|
| Emergency or urgent care visit | Immunocompetent adults | 26% (95% CI 23% to 29%) |
| Hospitalization | Immunocompetent adults | 35% (95% CI 30% to 40%) |
| Critical illness | Immunocompetent adults | 41% (95% CI 28% to 51%) |
| Hospitalization | Immunocompromised adults | 24% (95% CI 13% to 34%) |
CI = confidence interval.
Protection was strongest 7 to 59 days after vaccination and waned by 180 to 299 days. Critical illness was a composite outcome; component drivers were not reported.
Limitations
Observational design limits causal certainty. Electronic records may miss prior infection, home testing, and medical conditions. Sites covered only 6 states. Vaccinated patients were older and possibly higher risk, which may underestimate benefit.
Funding
CDC contracts; funder involved in study conduct.
Clinical Application
Recommend updated COVID-19 vaccination, especially for older and immunocompromised adults; protection is modest and appears strongest in the first 6 months.
Discussion
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In this test-negative case-control study, 2024-2025 COVID-19 vaccination was associated with lower COVID-19 hospitalization among immunocompetent adults (VE 35%, 95% CI 30%-40%); given the nonrandomized design and waning VE to 0% at 180-299 days, should this change counseling or booster timing? In this article, vaccine effectiveness against COVID-19–associated hospitalization was reported as 35% using VE = (1 − adjusted odds ratio) × 100%. Which interpretation is most appropriate?