2025-2026 COVID-19 Vaccines Cut Risk of Hospitalization Nearly in Half

Interim data from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION) show that the 2025-2026 COVID-19 vaccine provided meaningful additional protection against medically attended COVID-19 in adults during the early part of the respiratory virus season. Investigators led by researchers at the CDC, in partnership with Westat and several regional health systems, found vaccine effectiveness (VE) of 50% against emergency department (ED)/urgent care (UC) encounters and 55% against hospitalization among immunocompetent adults, using a test-negative design across sites in 7 states.¹

Study Design and Population

VISION is a multisite electronic health record-based network that, for this analysis, drew on 253 EDs/UCs and 179 hospitals operated by HealthPartners, Kaiser Permanente Northern California, Kaiser Permanente Northwest, Regenstrief Institute, and the University of Colorado. Investigators evaluated encounters among immunocompetent adults with COVID-19-like illness who underwent molecular or antigen SARS-CoV-2 testing from September 3, 2025, through December 31, 2025. Case patients tested positive for SARS-CoV-2, and control patients tested negative. Vaccination was defined as receipt of a 2025-2026 COVID-19 vaccine dose at least 7 days before the encounter, and odds ratios were adjusted for age, sex, race and ethnicity, calendar time, and geographic region.¹

The analysis included 85,725 ED/UC encounters, of which 3941 (5%) were cases, and 26,073 hospitalizations, of which 1022 (4%) were cases. Roughly 1 in 10 patients with an ED/UC encounter and roughly 1 in 8 hospitalized patients had received a 2025-2026 vaccine dose before their encounter.¹

Effectiveness Findings

VE against ED/UC encounters among all adults was 50% (95% CI, 42%-57%), at a median of 47 days since vaccination. VE against hospitalization was 55% (95% CI, 41%-66%), at a median of 46 days since vaccination. Among adults 65 years and older, VE was 48% (95% CI, 37%-56%) against ED/UC encounters and 53% (95% CI, 37%-65%) against hospitalization. Hospitalized patients had a substantially higher symptom burden than those seen in the ED/UC setting, with a median of 4 underlying medical condition categories compared with a median of zero among ED/UC patients.¹

The authors noted that circulating SARS-CoV-2 lineages during the study period were predominantly descendants of Omicron JN.1, a family that also includes the LP.8.1 strain targeted by the vaccine. Because SARS-CoV-2 circulation had increased shortly before the 2025-2026 vaccines became available, population-level immunity from recent infection may have been elevated going into the season, a factor the authors said could have contributed to somewhat lower VE estimates than would be expected in a population with less recent infection.¹

The study did not account for prior infection history or earlier vaccine doses, so the reported VE reflects added protection in a population with substantial existing immunity rather than protection from a fully unvaccinated, previously uninfected baseline.¹

The authors identified several limitations. Case patients may have sought emergency or hospital care for reasons other than COVID-19, which could understate true VE. Vaccination status may have been misclassified in ways that differed between cases and controls. Low rates of COVID-19-associated hospitalization and vaccination in some subgroups limited statistical power, preventing VE estimates for children; immunocompromised adults; adults 18 to 64 years specifically; critical illness outcomes; or effectiveness by time since vaccination. Residual confounding from unmeasured factors, such as behavioral precautions or use of outpatient antiviral treatment, may also remain.¹

A Fast-Moving Variant Landscape

The 2025-2026 vaccine formulations from Moderna, Pfizer-BioNTech, and Novavax are monovalent and based on the Omicron JN.1 lineage, using the LP.8.1 strain preferentially, per FDA guidance issued in May 2025.¹ JN.1 and its descendants have remained the dominant lineages worldwide since late 2023, with subvariants including KP.3, XEC, LP.8.1, NB.1.8.1, and XFG successively rising and falling in prevalence. By the fall of 2025, XFG had become the predominant lineage in the United States and in several other countries, which is antigenically related to the LP.8.1 strain used in the current vaccines. More recently, the more genetically distinct BA.3.2 lineage has been detected in increasing proportions in some surveillance systems, illustrating the pace at which new SARS-CoV-2 variants can emerge and spread.^2,3

This pattern of continual viral evolution is one reason public health agencies, including the FDA and World Health Organization, have moved to a process of periodically updating COVID-19 vaccine strain composition, similar to the approach long used for influenza vaccines.¹

Current Vaccination Recommendations

Vaccine policy for the 2025-2026 season differs from earlier COVID-19 vaccination campaigns. In September 2025, the Advisory Committee on Immunization Practices (ACIP) recommended that COVID-19 vaccination for people 6 months and older be based on individual, or shared clinical, decision-making between patients and their clinicians, rather than a universal recommendation. The recommendation notes that the benefit of vaccination is greatest for people at increased risk for severe COVID-19 and lowest for those without such risk factors. The CDC adopted this recommendation in October 2025.^4,5

This shift has drawn divergent responses from professional medical societies, some of which have published immunization schedules that differ from the federal schedule, and the change has also been the subject of ongoing litigation. A federal court stayed certain 2025 ACIP-driven changes to immunization schedules in March 2026, though the May 2025 COVID-19 vaccine recommendation was not affected by that stay.⁶ Pharmacists and other immunizing clinicians should confirm current federal and state guidance, as recommendations in this area have continued to evolve.

What This Means for Pharmacists

Pharmacists remain a primary point of access for COVID-19 vaccination and are often the clinicians best positioned to discuss individualized risk-benefit considerations under the current shared decision-making framework. The interim findings give pharmacists updated, season-specific effectiveness figures to reference in these conversations, particularly for older adults and patients with underlying conditions who face a higher likelihood of severe outcomes. Because the study period covered only the first several months of the 2025-2026 season, pharmacists should watch for updated CDC and VISION Network data as the season progresses.

REFERENCES

1. Wiegand RE, Chickery S, Yang DH, et al. Interim effectiveness of 2025-2026 COVID-19 vaccines in adults. Manuscript provided for review; VISION Network, Centers for Disease Control and Prevention, 2026.

2. Rijksinstituut voor Volksgezondheid en Milieu (RIVM). Variants of the coronavirus SARS-CoV-2. Accessed July 6, 2026. https://www.rivm.nl/en/coronavirus-covid-19/current/variants

3. US Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee briefing document, 2025-2026 COVID-19 vaccine strain considerations. Accessed July 6, 2026. https://www.fda.gov/media/192693/download

4. HHS.gov. ACIP recommends COVID-19 immunization based on individual decision-making. News release. US Department of Health and Human Services. September 19, 2025. Accessed July 6, 2026. https://www.hhs.gov/press-room/acip-recommends-covid19-vaccination-individual-decision-making.html

5. LeadingAge. COVID vaccine: CDC adopts ACIP recommendations for 2025/2026 schedules. October 7, 2025. Accessed July 6, 2026. https://leadingage.org/covid-vaccine-cdc-adopts-acip-recommendations-for-2025-2026-schedules/

6. Children's Hospital of Philadelphia. Locating the latest science-based vaccine recommendations. Accessed July 6, 2026. https://www.chop.edu/vaccine-update-healthcare-professionals/locating-latest-science-based-vaccine-recommendations