US study shows updated COVID vaccines cut hospitalization odds by 55%

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Jun 24 2026

In an early-season US analysis of more than 111,000 medically attended illness encounters, updated COVID vaccines showed meaningful added protection against emergency care and hospitalization among immunocompetent adults.

Study: Interim Estimated Effectiveness of 2025-2026 COVID-19 Vaccines in Adults Using a Test-Negative Design. Image Credit: Elena Pimonova / Shutterstock

In a recent study published in the journal JAMA Network Open, a large group of researchers in the United States evaluated the interim effectiveness of the 2025-2026 coronavirus disease 2019 (COVID-19) vaccines in preventing COVID-19-associated emergency department, urgent care, and hospital encounters among immunocompetent adults in the United States.

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Background

Despite widespread immunity from previous infections and vaccinations, COVID-19 was associated with an estimated 390,000 to 550,000 hospitalizations in the United States from October 2024 to September 2025.

Adults aged 65 years or older are still at greatest risk for severe outcomes, demonstrating the continued need for effective prevention strategies. As new virus strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, vaccines are regularly updated to better match circulating lineages.

It is important to monitor how well these updated vaccines protect actual practice so that this information can assist in developing public health recommendations, guiding clinical practice, and supporting patient and clinician decision-making about vaccination. Further research is needed to evaluate vaccine effectiveness in larger populations over a longer period of time.

About the study

The researchers conducted a case-control study using a test-negative design to evaluate the estimated effectiveness of the 2025-2026 COVID-19 vaccines among immunocompetent adults aged 18 years and older in the United States.

Data were obtained from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network, an electronic health record-based system that included 253 emergency department and urgent care facilities and 179 hospitals across seven states. Eligible encounters occurred between September 3 and December 31, 2025.

Researchers included adults with COVID-19-like illness identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) discharge diagnosis codes and tested for SARS-CoV-2, either directly by molecular testing (e.g., real-time reverse transcription-polymerase chain reaction) or by antigen assay.

Patients were included as cases defined by positive molecular or antigen test results for SARS-CoV-2, while controls had negative molecular test results. The vaccination status was determined from immunization information systems, electronic health record data, and medical claims data, where available.

Patients were considered vaccinated if they had received a 2025-2026 COVID-19 vaccine at least 7 days before the encounter. Patients were excluded if they were immunocompromised, had received multiple 2025-2026 vaccine doses, received a 2025-2026 dose less than two months after a previous COVID-19 vaccine dose, received a vaccine dose less than seven days before the encounter, had certain influenza or respiratory syncytial virus coinfections, or did not meet eligibility criteria required for vaccination.

Researchers used multivariable logistic regression models 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 combined emergency department/urgent care encounters and hospitalizations.

Study results

The analysis included 85,725 emergency department and urgent care encounters among immunocompetent adults with COVID-19-like illness. Patients positive for SARS-CoV-2 were identified as "cases" (n=3,941), while patients with negative molecular test results (n=81,784) were classified as "controls".

Overall, 9,659 individuals had received a COVID-19 vaccine in 2025-2026 before their encounter. Vaccination rates between cases and controls were significantly different: only 5% of cases were vaccinated, compared with 12% of controls.

Of all patients in emergency departments or urgent care facilities during this time period, 60% were between the ages of 18 and 64, and 60% were female. 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 during December 2025.

The estimated effectiveness of the 2025-2026 COVID-19 vaccine against COVID-19-associated emergency department and urgent care encounters among adults aged 18 years and older was 50% (95% confidence interval [CI], 42%-57%). The median time since vaccination was 47 days. Among adults aged 65 years and older, vaccine effectiveness against these medically attended encounters was 48% (95% CI, 37%-56%), with a median of 48 days since vaccination.

The hospitalization analysis included 26,073 adults admitted with COVID-19-like illness. In this study, 1,022 tested positive for SARS-CoV-2 and were classified as cases, while 25,051 tested negative by molecular testing and served as controls. A total of 3,140 hospitalized patients had received a 2025-2026 vaccine dose before admission. Vaccinated individuals accounted for 6% of cases and 12% of controls.

Among hospitalizations, the majority occurred among patients 65 years and older, with 67% of total hospitalizations, and women accounted for 54%. More than two-thirds of hospitalizations occurred among non-Hispanic White patients. December 2025 also recorded the largest number of hospitalizations during the study period.

In adults 18 years old and over, the estimated effectiveness of the COVID-19 vaccination against COVID-19-associated hospitalization was 55% (95% CI, 41%-66%) among people vaccinated at least 7 days earlier, with a median time since vaccination of 46 days. For adults 65 years and over, the vaccine was estimated to provide 53% effectiveness (95% CI, 37%-65%) against hospitalization, with a median time since vaccination of 46 days.

Conclusion

The researchers concluded that the 2025-2026 COVID-19 vaccines provided meaningful additional protection against medically attended COVID-19 among immunocompetent adults in the United States.

Vaccination was associated with lower odds of emergency department and urgent care encounters and hospitalization, even in a population with prior immunity from previous infections or vaccinations, although the analysis did not directly account for prior SARS-CoV-2 infection or prior COVID-19 vaccine doses. The overall protective benefit was observed among all adults aged 18 years or older and among adults aged 65 years or older, who face a greater risk of severe disease.

These findings support continued use of the updated vaccine formulation and suggest that vaccination can help reduce the likelihood of serious COVID-19-associated outcomes during the early 2025-2026 respiratory virus season, although the study did not assess protection over longer periods, against critical illness or death, in children, or in immunocompromised adults.