The 2025–2026 seasonal influenza vaccine reduced the risk of influenza-associated outpatient visits by 22% to 34% and hospitalizations by 30% with pediatric patients showing the strongest protection (38% to 41%), according to interim vaccine effectiveness estimates published March 12 in CDC's Morbidity and Mortality Weekly Report.
Researchers analyzed data from 142,494 patients with acute respiratory illness seen between September 2025 and February 2026 across three CDC surveillance networks: the New Vaccine Surveillance Network, the US Flu Vaccine Effectiveness Network, and the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network.
The study used a test-negative case-control design, comparing odds of vaccination among patients with laboratory-confirmed influenza with those who tested negative. Multivariable logistic regression was adjusted for study site, patient age, date of illness, and additional confounders; analyses from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network also adjusted for sex and race and ethnicity.
Findings in Pediatric Patients
Among pediatric patients aged 6 months through 17 years, vaccine effectiveness against any influenza-associated outpatient visit ranged from 38% to 41%, while vaccine effectiveness against hospitalization was 41%.
Against influenza A, outpatient vaccine effectiveness ranged from 37% to 38%, and hospitalization effectiveness reached 42%. For the predominant influenza A(H3N2) subtype, outpatient vaccine effectiveness was 35% and inpatient effectiveness was 38%.
Protection against influenza B outpatient visits was higher, with effectiveness estimates of 71% in the New Vaccine Surveillance Network and 45% in the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network.
In the US Flu Vaccine Effectiveness Network, estimates for pediatric patients against any influenza (14%), influenza A (10%), influenza A(H3N2) (2%), and influenza B (20%) were not statistically significant.
Findings in Adult patients
Among adult patients aged 18 years and older, vaccine effectiveness against any influenza-associated outpatient visit ranged from 22% to 34%, while effectiveness against hospitalization was estimated at 30% for any flu and influenza A.
For influenza A specifically, outpatient vaccine effectiveness was estimated at 34%. Against influenza B, outpatient vaccine effectiveness was 63%, although estimates for influenza A (21%), A(H3N2) (11%), and influenza B (23%) in the US Flu Vaccine Effectiveness Network were not statistically significant.
Among adults aged 18 to 64 years, outpatient vaccine effectiveness was estimated at 36% for any influenza and 35% for influenza A, with hospitalization effectiveness of 29% and 28%, respectively.
Among adults aged 65 years and older, outpatient vaccine effectiveness ranged from 30% to 41%, and hospitalization effectiveness was estimated at 31%.
Viral Surveillance Context
Genetic sequencing data through February 18, 2026 identified influenza A(H3N2) subclade K (J.2.4.1) in 83% of genetically characterized A(H3N2) viruses. The subclade is antigenically distinct from the 2025–2026 A(H3N2) vaccine virus (A/Croatia/10136RV/2023), which had been selected for the seasonal vaccine before the variant was first identified by CDC in June 2025.
Among 108 genetically characterized influenza B/Victoria viruses, 81% belonged to clade C.3.1, which also differs antigenically from the influenza B vaccine virus included in the 2025–2026 vaccine. Circulating influenza A(H1N1)pdm09 viruses remained similar to the vaccine strain.
Overall, influenza A(H3N2) accounted for 88% of subtyped influenza A specimens, and 93% of those belonged to the drifted subclade K strain.
Burden and Comparative Context
CDC estimated at least 26 million illnesses, 340,000 hospitalizations, and 21,000 deaths attributable to influenza in the US between October 1, 2025 and February 28, 2026.
As of February 21, 2026, approximately 48% of pediatric patients aged 6 months through 17 years and 47% of adults had received a 2025–2026 influenza vaccine.
The authors noted that interim US estimates for protection against outpatient visits were broadly consistent with contemporaneous data from China (24%), Canada (38% for influenza A), and Europe (37% to 40%). Hospitalization estimates were also similar to European findings ranging from 21% to 42%.
Limitations
The authors identified several limitations.
First, results are preliminary and may change as the influenza season continues.
Second, unmeasured confounding remains possible because underlying medical conditions and prior-season vaccination status were not modeled.
Third, vaccination status may have been misclassified because of self-reported vaccination, undocumented vaccinations received outside the medical system, and the two-dose series requirement for some children aged 6 months through 8 years.
Finally, limited sample sizes in certain strata prevented vaccine effectiveness estimates across all subgroups, including influenza A(H1N1)pdm09.
Differences in vaccine effectiveness estimates across the three surveillance networks may also reflect variations in case definitions for acute respiratory illness, surveillance approaches, outpatient care settings, and patient populations.
Implications
Even during a season with antigenically drifted circulating viruses, vaccination reduced influenza-associated morbidity.
The authors noted that during the 2022–2023 influenza season, overall vaccine effectiveness was similarly about 30%, yet vaccination was estimated to have prevented approximately 71,000 hospitalizations and 4,300 deaths.
They also emphasized that influenza antiviral medications remain an additional public health tool and should be started as early as possible for hospitalized patients or those at higher risk for complications.
CDC continues to recommend influenza vaccination for all eligible persons aged 6 months and older, and vaccines remain available.
“Receipt of a 2025–2026 influenza vaccine reduced the risk for influenza-associated outpatient visits and hospitalizations,” the authors concluded.
Source: CDC
