In an early-season analysis of more than 111,000 healthcare worker illness encounters in the United States, the latest coronavirus vaccines showed effective additional protection against emergency care and hospitalization in immunocompetent adults.
Study: Interim estimates of 2025-2026 COVID-19 vaccine efficacy in adults using a test-negative design. Image credit: Elena Pimonova / Shutterstock
In a recent study published in the journal JAMA network opena large group of U.S. researchers evaluated the preliminary efficacy of the 2025-2026 coronavirus disease (COVID-19) vaccines in preventing COVID-19-related emergency department visits, urgent care, and hospital encounters among immunocompetent adults in the United States.
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Despite widespread immunity from past infections and vaccination, there were an estimated 390,000 to 550,000 hospitalizations related to COVID-19 in the United States from October 2024 to September 2025.
Adults 65 years and older remain at highest risk for severe outcomes, indicating the continued need for effective prevention strategies. As new viral strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, vaccines are regularly updated to better match circulating strains.
It will be important to monitor how well these updated vaccines protect in real-world practice. In doing so, this information can help make public health recommendations, guide clinical practice, and support patient and clinician decision-making regarding vaccination. Further research is needed to evaluate the efficacy of the vaccine in larger populations over longer periods of time.
About research
Researchers conducted a case-control study using a test-negative design to evaluate the estimated efficacy of a 2025-2026 novel coronavirus disease (COVID-19) vaccine in immunocompetent adults aged 18 and older in the United States.
Data was obtained from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network, an electronic health records-based system that includes 253 emergency departments and urgent care facilities and 179 hospitals across seven states. The encounters of interest occurred between September 3, 2025 and December 31, 2025.
Researchers included adults with COVID-19-like illness who were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) hospital discharge diagnosis codes and who were tested for SARS-CoV-2 directly by molecular testing (such as real-time reverse transcription polymerase chain reaction) or antigen assay.
Patients were included as cases defined by a positive molecular or antigen test result for SARS-CoV-2, whereas controls had a negative molecular test result. Vaccination status was determined from the immunization information system, electronic medical record data, and medical claims data when available.
Patients were considered vaccinated if they had received the 2025-2026 novel coronavirus disease (COVID-19) vaccine at least 7 days before infection. Patients were excluded if they were immunocompromised, received multiple vaccinations in 2025-2026, received vaccination in 2025-2026 within 2 months of the previous COVID-19 vaccination, received vaccination within 7 days before infection, had certain influenza or RSV co-infections, or did not meet the required eligibility criteria for vaccination.
Researchers used a multivariable logistic regression model that adjusted for age, sex, race and ethnicity, calendar time, and geographic region to estimate vaccine effectiveness. Vaccine effectiveness was calculated from adjusted odds ratios and reported separately for the combination of emergency department/urgent care visits and hospitalizations.
Research results
The analysis included 85,725 emergency department and emergency care encounters among immunocompetent adults with a COVID-19-like illness. Patients testing positive for SARS-CoV-2 were identified as “cases” (n=3,941), and patients with negative molecular test results (n=81,784) were classified as “controls.”
Overall, 9,659 people were vaccinated before encountering COVID-19 in 2025-2026. There was a significant difference in vaccination rates between cases and controls, with only 5% of cases receiving vaccination compared to 12% of controls.
Of all patients admitted to emergency departments or urgent care facilities during this period, 60% were between the ages of 18 and 64, and 60% were women. Non-Hispanic white patients had the highest number of visits, followed by Hispanic or Latino patients, and then non-Hispanic black or African American patients. The highest number of encounters occurred in December 2025.
The estimated efficacy of the 2025-2026 COVID-19 vaccine against COVID-19-related emergency department and emergency care encounters in adults 18 years and older was 50% (95% confidence interval (CI), 42% to 57%). Median time since vaccination was 47 days. In adults 65 years and older, vaccine efficacy at these clinic visits was 48% (95% CI, 37% to 56%), with a median time of 48 days after vaccination.
The hospitalization analysis included 26,073 adults hospitalized with COVID-19-like illnesses. In this study, 1,022 people tested positive for SARS-CoV-2 and were classified as cases, while 25,051 people tested negative by molecular testing and served as controls. A total of 3,140 hospitalized patients had received the 2025-2026 vaccination prior to admission. Vaccinated people accounted for 6% of cases and 12% of controls.
Patients aged 65 years or older accounted for the most hospitalizations, accounting for 67% of all hospitalizations, and women accounted for 54%. More than two-thirds of hospitalizations involved non-Hispanic white patients. December 2025 also recorded the highest number of hospitalizations during the study period.
In adults 18 years and older, the estimated efficacy of COVID-19 vaccination against COVID-19-related hospitalizations was 55% (95% CI, 41% to 66%) for those vaccinated at least 7 days previously, with a median time since vaccination of 46 days. For adults 65 years and older, the vaccine was estimated to be 53% effective against hospitalization (95% CI, 37% to 65%), with a median time from vaccination of 46 days.
conclusion
Researchers concluded that the 2025-2026 COVID-19 vaccine provided meaningful additional protection against COVID-19 infection during health care visits among immunocompetent adults in the United States.
Even in populations with immunity from past infections or vaccination, vaccination was associated with lower odds of emergency department/ED encounters and hospitalization. However, this analysis did not directly account for previous SARS-CoV-2 infection or previous COVID-19 vaccination history. Overall protective effects were observed in all adults 18 years and older and in adults 65 years and older, who are at high risk for severe disease.
Although these findings support the continued use of modern vaccine formulations and suggest that vaccination may help reduce the likelihood of severe outcomes associated with COVID-19 infection early in the 2025-2026 respiratory virus season, this study did not assess long-term protective effects against severe disease or death in children or immunocompromised adults.
Reference magazines:
- Wiegand, RE, Chickery, S, Yang, DH-H, Ball, SW, DeSilva, MB, Dascombe, K, Irving, SA, Natarajan, K, Klein, NP, Grannis, SJ, Ong, TC, Lowry, EAK, Yates, A, Zhuang, Y, Wilson, S, McEvoy, CE, Essien, IJ. OO, Nailway, A.L., Coppol, P., Zerbo, O., Hansen, J.R., Jacobson, K.B., Block, L., Dixon, BE., Dudzinski, T., Rogerson, C., Baron, M.A., Chavez, C., Mack J., Ciesla, A.A., Godfrey, M., Kautz, A., Najdowski, M., Linkgels,. R., DeCure, J., Payne, AB (2026). Preliminary estimates of 2025-2026 COVID-19 vaccine efficacy in adults using a negative trial design. JAMA network open. 9(6). Doi: 10.1001/jamanetworkopen.2026.25152 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2850668
