Interim Estimated Effectiveness of 2025-2026 COVID-19 Vaccines in Adults Using a Test-Negative Design

Area of Science:

• Epidemiology
• Vaccinology
• Public Health

Background:

• The 2025-2026 COVID-19 vaccine targets prevalent JN.1 and its sublineages, becoming available in September 2025.
• Assessing the effectiveness of this new vaccine is crucial for public health strategies against circulating SARS-CoV-2 variants.

Purpose of the Study:

• To estimate the interim effectiveness of the 2025-2026 COVID-19 vaccines.
• To evaluate protection against medically attended COVID-19 in immunocompetent US adults aged 18 years and older.

Main Methods:

• A test-negative case-control study design was employed.
• Data were collected from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (comprising 253 ED/UCs and 179 hospitals across 7 states) from September 3 to December 31, 2025.
• Vaccine effectiveness was calculated as (1 - adjusted odds ratio) × 100% comparing vaccinated and unvaccinated individuals with COVID-19-like illness.

Main Results:

• The 2025-2026 vaccine showed an estimated 50% effectiveness against COVID-19-associated emergency department/urgent care encounters (95% CI, 42%-57%).
• Estimated effectiveness against COVID-19-associated hospitalization was 55% (95% CI, 41%-66%).
• Effectiveness was observed in both younger adults and those aged 65 years and older, with VE against hospitalization at 53% for the older group.

Conclusions:

• The 2025-2026 COVID-19 vaccination provides additional protection against medically attended COVID-19 outcomes.
• These findings underscore the importance of obtaining the updated vaccine to reduce the risk of severe COVID-19 illness and hospitalization.