Analyses were conducted utilizing data from four CDC-affiliated vaccine effectiveness (VE) networks, each employing a test-negative, case-control design to assess influenza vaccine effectiveness. The networks include: 1) Investigating Respiratory Viruses in the Acutely Ill (IVY), 2) the New Vaccine Surveillance Network (NVSN), 3) U.S. Flu Vaccine Effectiveness (U.S. Flu VE), and 4) the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION). These analyses encompass both child and adolescent patients as well as adults who sought medical care (either outpatient or inpatient) for an acute respiratory illness (ARI) during the 2024–25 influenza season.
In this study, case-patients were defined as individuals with ARI who tested positive for influenza via a molecular assay. In contrast, control patients were those diagnosed with ARI but yielded negative results on the influenza test. Notably, the demographic and clinical characteristics of enrolled patients varied across the different networks. For instance, IVY primarily enrolled hospitalized patients aged ≥18 years, while NVSN catered to child and adolescent patients (aged 6 months–17 years) in both outpatient and inpatient settings. Similarly, U.S. Flu VE focused on child and adolescent (aged 8 months–17 years) and adult patients (≥18 years) in outpatient care, while VISION included both groups across outpatient and hospitalized settings.
To evaluate the impact of vaccination on the likelihood of influenza illness, vaccine effectiveness (VE) was calculated using the formula (1 − adjusted odds ratio) × 100%, employing multivariable logistic regression. This analysis adjusted for variables such as geographic region, age, calendar time of illness, and other predefined confounders. Patients were categorized as vaccinated if they had received at least one dose of the 2024–2025 seasonal influenza vaccine at least 14 days prior to the onset of ARI or clinical encounter. Those vaccinated less than 14 days before the index date or who tested positive for SARS-CoV-2 were excluded from the study.
The IVY, NVSN, and U.S. Flu VE networks calculated VE against influenza A virus subtypes A(H1N1)pdm09 and A(H3N2) when feasible. The report includes VE point estimates for each network, along with 95% confidence intervals (CIs). A 95% CI that excludes zero was considered statistically significant. For every network and patient age group, VE and the corresponding 95% CIs were interpreted as the percentage of specific influenza outcomes prevented. The analyses utilized SAS software (version 9.4) and R (version 4.4) to process the data. Activities from IVY, NVSN, and U.S. Flu VE were reviewed by the CDC, deemed non-research, and conducted in compliance with federal law and CDC policy. VISION activities also underwent CDC review and adhered to federal regulations.
The data garnered from the IVY network consisted of 3,175 hospitalized adult patients aged ≥18 years with ARI. Meanwhile, NVSN included 4,611 patients under the age of 18 with ARI, which comprised 2,969 patients seen in outpatient settings and 1,642 who were hospitalized. Outpatient data from the U.S. Flu VE network covered 3,344 ARI patients, with 1,134 being children and adolescents, and 2,210 adults. VISION data incorporated 139,558 outpatient encounters (36,919 among patients aged
Among control patients (those with ARI and a negative influenza test result) aged
For individuals aged
For adults aged ≥18 years, VE against any influenza-associated ARI was 36% (U.S. Flu VE) and 54% (VISION) in outpatient settings, with VE against hospitalization recorded at 41% (IVY) and 55% (VISION). Effectiveness against influenza A(H1N1)pdm09 was 42% in outpatient settings (U.S. Flu VE), while no significant effectiveness was observed for hospitalization in the IVY network (39%; 95% CI = −14% to 67%). The effectiveness against influenza A(H3N2) was noted to be 51% (IVY) for hospitalization but was not statistically significant in outpatient settings (25%; 95% CI = −6% to 48%, U.S. Flu VE network). For adults aged 18–64 years, VE against any influenza-associated ARI in outpatient settings was 37% (U.S. Flu VE) and 56% (VISION); VE against hospitalization was 48% (IVY) and 51% (VISION). Among adults aged ≥65 years, VE for outpatient settings was 51% (VISION) and 38% (IVY) against hospitalization, with the U.S. Flu VE network showing no significant VE (18%; 95% CI = −69% to 60%).
As of February 3, 2025, a total of 286 influenza A(H3N2) viruses were genetically characterized: 26 (9%) from IVY, 200 (70%) from the U.S. Flu VE network, and 60 (21%) from NVSN, all belonging to the hemagglutinin (HA) clade 2a.3a.1, which includes the A(H3N2) strain selected for the 2024–2025 cell-grown influenza vaccine (A/Massachusetts/18/2022). In addition, among 158 sequenced A(H1N1)pdm09 viruses, five (3%) were from IVY, 80 (51%) from the U.S. Flu VE network, and 73 (46%) from NVSN. The HA clade 5a.2a includes the A(H1N1)pdm09 strain selected for the 2024–2025 cell-grown influenza vaccine (A/Wisconsin/67/2022).
The interim estimates of the 2024–25 VE indicate that influenza vaccination effectively prevented medically attended influenza-associated illnesses in both children and adults in the United States. The VE for children and adolescents against medically attended influenza varied from 32% to 60% in outpatient settings and from 63% to 78% against influenza-associated hospitalization. In adults, the VE against medically attended influenza was 36% and 54% in outpatient settings, with hospitalization VE ranging from 41% to 55%.
Despite an increase in the circulation of influenza A(H3N2) viruses—typically associated with lower VE—the estimates from this influenza season were consistent with the previous 2023–24 season and seasons with higher VE over the past 15 years. These findings align with interim estimates from Canada for the 2024–25 influenza season, which reported a 54% overall VE, and estimates from South America for the 2024 southern hemisphere influenza vaccine, which indicated a 34% overall VE against influenza A.
Given the high levels of influenza activity and severity in the United States this season, enhancing influenza vaccination rates could significantly mitigate influenza-associated illnesses, medical visits, hospitalizations, and fatalities. The VE estimates and associated confidence intervals presented in this report may reflect regional variations in circulating viruses. Notably, in the U.S. Flu VE network, 67% of subtyped influenza A specimens were influenza A(H3N2), compared to 48% in NVSN. The U.S. Flu VE network did not find statistically significant VE against influenza A(H3N2) in outpatient settings among child and adolescent patients or adult patients, mirroring findings from the 2018–19 season and results observed in Europe during the 2024–25 influenza season.
To address ongoing evolutionary changes in the influenza virus, the composition of influenza vaccines is reviewed annually and adjusted to safeguard against the influenza viruses predicted to be most prevalent in the upcoming season. When circulating viruses diverge antigenically from the vaccine strains, the VE can diminish.
This report acknowledges several limitations. First, the VE estimates are preliminary, and final estimates may vary as influenza continues to spread throughout the 2024–25 season. Second, there may be misclassification of influenza vaccination status in some networks, potentially affecting VE calculations. Vaccines administered in pharmacies are typically reported to jurisdictional immunization information systems (IISs), but vaccinations conducted in non-traditional environments, such as workplaces, may not be documented in IISs. Third, while patients who received at least one dose of the 2024–2025 influenza vaccine were classified as vaccinated, children aged 6 months–8 years are advised to receive two doses if they have not previously received two doses. Consequently, some children labeled as vaccinated may not have been fully immunized, which could lead to lower VE estimates. Lastly, unmeasured confounding factors may exist, as networks did not account for variables such as previous vaccinations, past influenza virus infections, or underlying health conditions.
Vaccination remains the most effective method to prevent influenza and associated hospitalizations. The findings from this report indicate that vaccination with the 2024–2025 influenza vaccine significantly reduced the likelihood of medically attended influenza cases. This underscores the CDC’s recommendation for all individuals aged ≥6 months to receive the influenza vaccine. Additionally, these findings highlight the robust protective effect that influenza vaccination has against severe influenza-related complications, reinforcing the importance of vaccination in reducing the risks associated with influenza.
Eligible individuals aged ≥6 months who have yet to receive the 2024–2025 influenza vaccine are strongly encouraged to get vaccinated while influenza viruses continue to circulate in their communities.
