TOPLINE

Influenza vaccination during the 2024-2025 season reduced the risk for influenza-associated hospitalization by 40% among US adults, with similar protection across age groups and influenza A subtypes. Vaccination also reduced the risk for severe in-hospital outcomes, including ICU admission and death.

METHODOLOGY

• Researchers conducted a test-negative case-control study to estimate influenza vaccine effectiveness (VE) among adults hospitalized with acute respiratory illness across 26 medical centers from October 2024 to April 2025.
• They analyzed 6109 patients, including 1735 influenza case patients and 4374 control patients. Case patients were those in whom the influenza virus was detected on local clinical testing, centralized reverse transcription polymerase chain reaction testing, or both.
• Researchers compared vaccination odds between case and control patients using multivariable logistic regression, adjusting for age group, sex, race/ethnicity, Census region, and enrollment month and year.
• The primary outcome was influenza-associated hospitalization; in-hospital outcomes were the use of standard oxygen therapy, noninvasive advanced respiratory support, or invasive organ support; ICU admission; and death.
• Among case patients with influenza A, 53% were successfully subtyped as A(H1N1)pdm09 and 39% were subtyped as A(H3N2).

TAKEAWAY

• VE against influenza-associated hospitalization was 40%, with similar protection across age groups: 50% for adults aged 18-49 years, 41% for those aged 50-64 years, and 39% for those aged 65 years or older. 
• VE against hospitalization was similar overall for A(H1N1)pdm09 (41%) and A(H3N2) (43%). For A(H3N2), however, VE was lower among adults aged 65 years or older (34%) than among those aged 18-64 years (58%).
• VE was 47% among immunocompetent patients, whereas no significant protection was observed among immunocompromised patients (VE, 7%). VE was 48% in immunocompetent patients with 0-3 chronic conditions and 31% in those with four or more such conditions.
• Vaccination reduced the risk for severe in-hospital outcomes, with VE of 41% for the use of standard oxygen therapy, 38% for the use of noninvasive advanced respiratory support, 58% for both the use of invasive organ support and ICU admission, and 52% for death.
•  After stratification by influenza A subtype, vaccination remained effective against all severe in-hospital outcomes except A(H3N2)-associated hospitalization with noninvasive advanced respiratory support and A(H3N2)-associated hospitalization with death.

IN PRACTICE

"During the 2024–2025 U.S. influenza season, characterized by sustained elevated activity, we observed significant protection from seasonal influenza vaccination against influenza-associated hospitalizations in adults overall, for influenza B and both influenza A(H1N1)pdm09 and A(H3N2) subtypes, and for all age groups, but without evidence of protection for patients with immunocompromising conditions," the authors of the study wrote.

SOURCE

The study was led by Nathaniel M. Lewis, PhD, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention in Atlanta. It was published online on September 26, 2026, in Clinical Infectious Diseases.

LIMITATIONS

Statistical power was restricted for several estimates of vaccine effectiveness against in-hospital outcomes, which reduced the precision of results for rare outcomes. Residual confounding may have existed due to differences in health status and risk profiles between case and control patients not captured by measured confounders, such as frailty. Some important outcomes like influenza pneumonia may not have been fully captured.

DISCLOSURES

The study was supported by grants from the Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, and the National Institutes of Health. Lewis was employed by Merck and received a salary and stock from the company outside the submitted work. He conducted the study while employed at the CDC. Several authors reported receiving grants, consulting fees, research support, or honoraria from pharmaceutical companies and other organizations, including support unrelated to this work. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.