Influenza Activity and Estimated Vaccine Effectiveness During the 2025-2026 Influenza Season

This surveillance study characterizes influenza activity (ie, virus type, antiviral susceptibility, immunogenicity, and influenza-associated outpatient and emergency department visits, hospitalizations, and mortality) and estimated vaccine effectiveness during the 2025-2026 influenza season.

Key Points

Question

How severe is the 2025-2026 US influenza season, and are existing mitigation measures, such as antivirals and vaccines, effective?

Findings

This surveillance study of influenza data from September 2025 through March 2026 indicated a moderately severe influenza season during which antigenically drifted A(H3N2) viruses predominated but influenza antiviral medications and vaccines were still estimated to be effective.

Meaning

These findings highlight that monitoring influenza activity is critical for understanding the risk and burden of influenza and the benefits of existing interventions.

Abstract

Importance

Antigenically drifted influenza A(H3N2) J.2.4.1 (subclade K) viruses predominated during the 2025-2026 Northern Hemisphere influenza season.

Objective

To describe influenza activity and burden, characterize subclade K, evaluate susceptibility to influenza antivirals and postinfluenza vaccination antibodies, and estimate vaccine effectiveness.

Design, Setting, and Participants

This surveillance study used multiple data sources, including (1) national surveillance of influenza-positive respiratory specimens collected by approximately 300 clinical laboratories and 100 public health laboratories from October 1, 2025, through March 14, 2026, a subset of which were further characterized; (2) serologic data of people who received 2025-2026 influenza vaccines; (3) influenza admissions data from the Influenza Hospitalization Surveillance Network (ie, 10% of US population) and the associated estimates of US burden; and (4) test-negative, case-control vaccine effectiveness estimates from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network.

Exposures

Influenza infection, hospitalization, and vaccination.

Main Outcomes and Measures

Outcomes included influenza virus type, subtype, and clade; antiviral susceptibility; immunogenicity; influenza-associated outpatient and emergency department visits, hospitalizations, and mortality; estimated influenza illnesses, hospitalizations, and death; and estimated vaccine effectiveness.

Results

As of March 14, 2026, of the 55 318 influenza-positive respiratory specimens tested by public health laboratories, most (50 291 specimens [90.9%]) were influenza A, of which 40 779 (81.1%) were subtyped and 35 801 (87.8%) were A(H3N2). Of the 1754 characterized A(H3N2) viruses, most (1626 specimens [92.7%]) were subclade K. Postinfluenza vaccination neutralizing geometric mean antibody titers against subclade K were reduced 1.62 (95% CI, 1.29-2.02)–fold compared with the vaccine virus. All 1729 tested A(H3N2) viruses were sensitive to antivirals. Of the 27 881 recorded influenza hospitalizations, 15 426 (54.7%) were among female patients, and 15 051 (54.0%) were among patients aged 65 years or older. The estimated cumulative influenza-associated hospitalization rate was 80.0 per 100 000 which would correlate with estimates of between 28 000 000 to 49 000 000 illnesses, 360 000 to 740 000 hospitalizations, and 22 000 to 74 000 deaths in the US during the 2025-2026 season. Adjusted interim vaccine effectiveness estimates against influenza-associated emergency department or urgent care encounters and hospitalizations were 35% (95% CI, 33%-38%) and 27% (95% CI, 21%-34%), respectively.

Conclusions and Relevance

This surveillance study found that while antigenically drifted viruses predominated and caused substantial morbidity and mortality, influenza vaccines were associated with a reduced risk of influenza among those who were vaccinated, and recommended antivirals remained effective.

Introduction

Influenza surface proteins accumulate amino acid changes to escape population immunity. During systematic surveillance activities early in August 2025, the Centers for Disease Control and Prevention (CDC) identified 10 mutations in the hemagglutinin (HA) surface protein of influenza A(H3N2) viruses compared with the Northern Hemisphere 2025-2026 influenza vaccine virus component. These included changes at residues K2N, T135K(CHO−), S144N(CHO+), N145S, N158D, I160K, Q173R, K189R, T328A, and S378N.^1,2 While influenza viruses are constantly changing, the location of these changes (around receptor and antibody binding sites), the changes in the glycosylation patterns, and the number of changes raised concerns that these viruses might evade vaccine-induced antibodies. Antigenic characterization³ by HA inhibition (HI) also demonstrated these influenza A(H3N2) viruses had evidence of antigenic drift compared with the vaccine reference virus and led the CDC to elevate the viruses for reagent production, candidate vaccine virus development, and to alert partners in the Global Influenza Surveillance and Response System.

Since September 2025, the Global Influenza Surveillance and Response System reported that the rapid emergence and spread of influenza A(H3N2) viruses, now named subclade K viruses because they displaced other influenza viruses, caused a protracted influenza epidemic in Australia,⁴ an early and severe influenza season in Japan,⁵ and became predominant in the Northern Hemisphere.^6,7,8 In this study, we provide US virologic, immunologic, and epidemiologic findings from September 2025 through March 2026, including burden and vaccine effectiveness (VE) data. This information can help the public and health practitioners better assess the risk of influenza and inform decisions about targeted medical countermeasures.

Methods

All activities of this surveillance study were reviewed by the CDC and conducted consistently with applicable federal law and CDC policy (45 CFR part 46, 21 CFR part 56; 42 USC. Section 241(d); 5 USC Section 552a; 44 USC Section 3501 et sequens). Clinical and public health laboratory data are considered surveillance and exempt from ethics approval in accordance with 45 CFR part 46. The Influenza Hospitalization Surveillance Network (FluSurv-NET) sites obtained human participants and ethics approval from their respective state health department, academic partners, or hospital institutional review boards as needed. Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION) activities were reviewed by the CDC and were deemed not research or research not involving human participants. The use of sera was approved by the CDC as human participant research; written informed consent was obtained for sera collection from participants or the parent or guardian of minors, and minors provided verbal assent.

Surveillance

US influenza virus surveillance is a collaboration between CDC and partners⁹ including about 300 clinical laboratories and 100 public health laboratories located throughout all 50 states, Puerto Rico, Guam, and the District of Columbia, which report data to CDC. Clinical laboratories primarily test respiratory specimens for diagnostic purposes, and their data are used to track the timing and intensity of influenza activity. Public health laboratories primarily test specimens for surveillance purposes to identify influenza virus types, subtypes, and clades.

Genetic and Antigenic Characterization

Public health laboratories submit influenza-positive specimens to the CDC in accordance with the Influenza Virologic Surveillance Right Size Roadmap¹⁰ and specimen submission guidance.¹¹ All received specimens underwent viral genomic sequencing and were genetically characterized by HA clade and subclade.¹² A purposive subset was selected for antigenic characterization based on the genetic changes in their surface proteins. Antigenic characterization was performed using antisera raised in ferrets infected with 2025-2026 vaccine reference. HI assays³ were performed for selected A(H1N1)pdm09, A(H3N2), and B/Victoria viruses using ferret antisera. Viruses were deemed antigenically similar to vaccine reference viruses when their titer differences were reduced by 4-fold or less relative to the homologous ferret antiserum titers. The CDC also assessed susceptibility of influenza viruses to antiviral medications using sequence data analysis to detect amino acid substitutions known or suspected to reduce susceptibility to oseltamivir, zanamivir, peramivir, and baloxavir.¹³ A purposive subset of viruses was tested for susceptibility to neuraminidase inhibitors oseltamivir, zanamivir, and peramivir using a neuraminidase inhibition assay.¹⁴ Susceptibility to baloxavir was assessed using the cell culture-based Influenza Replication Inhibition Neuraminidase-Based Assay.¹⁵

Vaccine Immunogenicity

Anonymous preinfluenza and 21- to 28-day postinfluenza vaccination sera samples were collected from children aged 3 to 8 years and adults aged 18 to 49 years who received cell culture–based influenza vaccine and from older adults aged 65 years or older who received high-dose, inactivated, egg-based influenza vaccine during the 2025-2026 influenza season in the US. Sera were first prescreened against cell-grown vaccine viruses to select vaccine responders. Sera from 20 children, 20 adults, and 20 older adult vaccine responders were used for microneutralization assays using MDCK-SIAT1 cells to measure neutralizing antibody responses against MDCK-SIAT1 grown A(H3N2) viruses including vaccine virus A/District of Columbia/27/2023, and circulating viruses from genetic groups J.2.3, J.2.4, J.2.5, and K subclades.¹⁶ Prevaccination and postvaccination geometric mean titers (GMTs) of neutralizing antibodies were calculated from each vaccine group. Percentage seropositivity was defined as proportions of participants with neutralizing antibodies at a level of titer 40 or greater.

Statistical Analysis

Incidence and Burden

FluSurv-NET conducts population-based surveillance of laboratory-confirmed influenza hospitalizations in patients of all ages in select counties in 14 states, covering approximately 10% of the US population. Medical record abstractions were conducted on a stratified random sample of FluSurv-NET cases to obtain detailed clinical data on influenza-associated hospitalizations, including the proportion treated with influenza antiviral medications and requiring intensive care. Race and ethnicity data were abstracted from the medical record. For this analysis, categories of race and ethnicity included non-Hispanic Black, Hispanic, non-Hispanic White, and other (American Indian or Alaskan Native, Asian or Pacific Islander, multiracial, or missing); race and ethnicity data were included because influenza-associated hospitalization rates are known to differ across racial and ethnic groups. The CDC uses FluSurv-NET findings to generate weekly age-stratified influenza hospitalization rates.

To model influenza disease burden, the CDC uses age-specific hospitalization rates from FluSurv-NET to estimate influenza-associated symptomatic illnesses, medical visits, hospitalizations, and deaths for the US, adjusted for possible underdetection by accounting for testing practices at FluSurv-NET sites and the sensitivity of the diagnostic tests used. Adjusted rates are then multiplied by the US Census population to obtain influenza-associated hospitalizations. Age-specific illness to hospitalization ratios are applied to obtain the number of illnesses. Then age-specific illness to care seeking ratios are applied to obtain the number of outpatient influenza illnesses. Finally, age-specific death to hospitalization ratios are multiplied by age-specific hospitalizations to obtain the number of estimated deaths due to influenza. To classify the severity of the 2025-2026 influenza season compared with past seasons, the Moving Epidemic Method was used across all ages and by 3 age groups (0 to 17 years, 18 to 64 years, and ≥65 years) utilizing surveillance data for influenza-like illnesses, hospitalizations, and deaths.¹⁷ Weekly values for each of the indicators were compared with threshold values–based historic peak activity values and classified as low, moderate, high, or very high severity.

Estimated Vaccine Effectiveness

The CDC estimates vaccine effectiveness (VE) against influenza outpatient encounters and hospitalizations through 3 CDC-affiliated networks¹⁸; in this study, we provide interim findings from our electronic health record–based platform: VISION. Detailed methods have been previously published.¹⁹ Briefly, VE was measured using a test-negative, case-control design.¹⁹ Cases tested positive for influenza using molecular diagnostic assays and controls tested negative. Influenza vaccination status was determined through jurisdictional immunization registries, electronic health records, or claims data. Patients were considered vaccinated if they had received 1 or more doses of 2025-2026 influenza vaccine 14 days or more prior to the encounter index date.²⁰ Encounters were excluded from analyses if they tested positive for SARS-CoV-2 to reduce potential bias due to correlated influenza and COVID-19 vaccination behaviors. VE was estimated as 1 minus the adjusted odds ratio (multiplied by 100) from multivariable logistic regression, adjusting for age, sex, race and ethnicity, calendar time of illness, and study site. Race and ethnicity data were collected from the electronic health record. Categories included non-Hispanic Black, Hispanic, non-Hispanic White, other (American Indian or Alaska Native, Asian, Hawaiian or Other Pacific Islander, Middle Eastern or North African, multiracial, or other [any race or ethnicity not otherwise specified]), and unknown. Race and ethnicity were included to account for known disparities in influenza vaccination and disease. VE estimates were considered statistically significant if their confidence intervals did not include the null. Analyses were conducted using SAS software version 9.4 (SAS Institute) and R version 4.5 (R Foundation).

Results

Surveillance

From September 28, 2025, to March 14, 2026, clinical laboratories reported influenza test results from 1 939 806 specimens, of which 281 329 (14.5%) were positive for influenza (Table 1). Of these positive specimens, 218 833 (77.8%) were positive for influenza A and 62 496 (22.2%) were positive for influenza B (Figure 1). Influenza detections increased in November 2025, with most US Health and Human Services regions peaking during the week ending on December 27, 2025, which was within the US historical norm. Public health laboratories tested 80 834 samples, of which 55 318 were positive for influenza; of these, 50 291 (90.9%) were positive for influenza A and 5027 (9.1%) were positive for influenza B. Among the 40 779 subtyped influenza A viruses (81.1%), 35 801 (87.8%) were influenza A(H3N2), 4976 (12.2%) were influenza A(H1N1)pdm09, and 2 (<0.1%) were influenza A(H5). Among the 1785 (35.5%) influenza B viruses with lineage testing, all were B/Victoria.

Table 1. Influenza Virologic Surveillance, US, September 28, 2025, Through March 14, 2026^a.

Week ending date	Public health laboratoriesb								Clinical laboratoriesc
	Laboratories reporting, No.	Specimens tested, No.	Influenza A (not subtyped) specimens, No.	AH/1N1 pdm09 specimens, No.	A/H3N2 specimens, No.	Influenza B specimens (not lineage tested), No.	Influenza B/Victoria lineage specimens, No.	Influenza B/Yamagata lineage specimens, No.	Laboratories reporting, No.	Specimens tested, No.	Positive specimens, No. (%)	Influenza A–positive, No.	Influenza B–positive, No.
October 4, 2025	85	985	5	62	43	5	4	0	268	55704	289 (0.5)	243	46
October 11, 2025	83	952	6	52	65	5	1	0	266	57 031	301 (0.5)	257	44
October18, 2025	84	1050	10	68	108	6	2	0	270	55 540	358 (0.6)	307	51
October25, 2025	83	1181	11	114	139	3	7	0	260	56 778	446 (0.8)	399	47
November 1, 2025	85	1262	9	77	187	10	3	0	262	56 046	615 (1.1)	553	62
November 8, 2025	88	1547	16	138	431	14	6	0	268	61 928	1180 (1.9)	1060	120
November 15, 2025	87	1747	21	175	670	24	11	0	267	62 987	2057 (3.3)	1877	180
November 22, 2025	88	2371	51	207	1049	61	13	0	263	66 135	3619 (5.5)	3334	285
November 29, 2025	86	2467	137	206	1301	33	18	0	268	63 026	5059 (8.0)	4766	293
December 6, 2025	90	3465	235	204	1733	51	24	0	263	73 017	6537 (9.0)	6204	333
December 13, 2025	90	4756	734	248	2512	43	25	0	263	82 704	12 733 (15.4)	12 134	599
December 20, 2025	91	6946	1586	300	3686	78	33	0	265	105 746	26 968 (25.5)	25 590	1378
December 27, 2025	90	7643	1837	322	4203	93	50	0	263	119 874	37 979 (31.7)	35 909	2070
January 3, 2026	91	7549	1745	372	4003	106	40	0	265	117 383	28 864 (24.6)	27 191	1673
January 10, 2026	90	6528	1186	313	3196	118	38	0	264	108 393	20 016 (18.5)	18 609	1407
January 17, 2026	91	4817	619	287	2318	112	68	0	264	95 697	16 245 (17.0)	14 748	1497
January 24, 2026	91	4378	329	316	2312	145	81	0	269	91 774	16 053 (17.5)	13 635	2418
January 31, 2026	91	3766	229	264	1854	198	137	0	269	87 953	15 287 (17.4)	12 053	3234
February 7, 2026	91	4134	204	303	1841	287	153	0	254	94 316	17 012 (18.0)	11 918	5094
February 14, 2026	91	3710	188	268	1385	334	216	0	249	95 053	17 463 (18.4)	9860	7603
February 21, 2026	91	3380	161	244	1101	501	280	0	262	96 391	17 439 (18.1)	7663	9776
February 28, 2026	88	2779	94	212	820	382	267	0	261	92 016	14 546 (15.8)	5150	9396
March 7, 2026	87	2367	71	157	621	436	221	0	251	84 052	12 626 (15.0)	3580	9046
March 14, 2026	83	1054	28	67	223	197	87	0	174	60 262	7637 (12.7)	1793	5844

^a Influenza virologic surveillance in the US is described by the Centers for Disease Control and Prevention (data available as of March 18, 2026).²¹

^b Public health laboratories primarily test specimens for surveillance purposes to understand what influenza virus types, subtypes, and lineages are circulating. These laboratories often test prescreened positive specimens, so calculating percentage of positive specimens is not a reliable indicator of intensity of influenza activity.

^c Clinical laboratories primarily test respiratory specimens for diagnostic purposes, and data from these laboratories provide useful information on the timing and intensity of influenza activity through the percentage of specimens testing positive for influenza.

Figure 1. Bar and Line Graph of Influenza-Positive Tests Reported to the Centers for Disease Control and Prevention by US Clinical Laboratories, National Summary, 2025-2026 Season.

The bars show the number of specimens positive for influenzas A and B, while lines show the percentage of positive specimens.

Genetic and Antigenic Characterization

From September 28, 2025, to March 14, 2026, the CDC had genetically characterized 2848 of the 55 318 specimens positive for influenza at public health laboratories. Of these, 1754 were influenza A(H3N2), 634 were influenza A(H1N1)pdm09, and 460 were influenza B/Victoria lineage viruses. Most characterized A(H3N2) viruses (1626 specimens [92.7%]) belonged to clade 2a.3a.1 subclade K, while the rest belonged to other clade 2a.3a.1 subclades (ie, J.2, J.2.2, J.2.3, and J.2.4) (Figure 2). Of the subclade K viruses, 618 (38.0%) had identical HA protein sequences possessing only the subclade-defining amino acid changes. Most characterized A(H1N1)pdm09 viruses (631 viruses [99.5%]) were clade 5a.2a.1, of which 226 (35.6%) were subclade D.3.1 and 405 (63.9%) were subclade D.3.1.1. All 460 B/Victoria lineage viruses belonged to clade 3a.2; of these, 292 (63.5%) were subclade C.3.1 and the remainder were subclades C.3, C.5.1, C.5.6, C.5.6.1, and C.5.7.

Figure 2. Bar Graph of Genetic Characterization of Hemagglutinin Genes Based on Phylogenetic Analysis.

Numbers of hemagglutinin viruses characterized by clades and subclades are shown, along with the percentage of viruses belonging to each clade and subclade within the subtype. Data as of March 14, 2026, are shown.

During the same period, the CDC antigenically characterized 196 influenza A(H3N2) viruses, 150 A(H1N1)pdm09 viruses, and 99 B/Victoria lineage viruses. Among the viruses tested, 4 A(H3N2) viruses (2.0%), 147 A(H1N1)pdm09 viruses (98.0%), and 32 B/Victoria (32.3%) viruses were antigenically similar to their respective current-season influenza vaccine reference virus.²²

The CDC also assessed the antiviral susceptibility of 2790 influenza viruses (1729 A(H3N2), 615 A(H1N1)pdm09, and 446 B/Victoria). Most viruses, including all A(H3N2) subclade K viruses, were susceptible to the influenza antiviral medications oseltamivir, peramivir, zanamivir, and baloxavir. Four A(H1N1)pdm09 viruses had the H275Y amino acid substitution in the neuraminidase known to confer resistance to oseltamivir and peramivir. Twelve A(H1N1)pdm09 viruses had amino acid substitutions I223V and S247N in the neuraminidase and displayed reduced inhibition by oseltamivir. Two B/Victoria viruses had M464T amino acid substitution in the neuraminidase and displayed reduced inhibition by peramivir.

Vaccine Immunogenicity by Age Group

Among the prevaccination and postvaccination sera from healthy vaccine responders (20 children aged 3 to 8 years, 20 adults aged 18 to 49 years, and 20 adults aged 65 years or older), all achieved seropositivity postvaccination to the cell-grown A/District of Columbia/27/2023 A(H3N2) vaccine virus. Vaccination also induced significant cross-reactive neutralizing antibody responses against representative circulating A(H3N2) viruses in diverse genetic groups from J.2.3, J.2.4, J.2.5 and subclade K viruses (comparing postvaccination vs prevaccination geometric mean titers of each virus from J.2.3, J.2.4, and J.2.5 and subclade K). However, the levels of postvaccination neutralizing antibody titers against a representative subclade K virus (cell-grown A/Wisconsin/114/2025) were reduced; the geometric mean fold reduction was 1.62 (95% CI, 1.29-2.02) when the subclade K postvaccination geometric mean titers were compared with those of the vaccine virus across the 3 age groups. Nevertheless, sera from all 20 children, 18 adults aged 18 to 49 years (90.0%), and 18 adults aged 65 years or older (90.0%) had postvaccination neutralizing antibodies at a titer 40 or greater to the subclade K virus.

Incidence, Burden, and Clinical Characteristics

From October 1, 2025, through March 14, 2026, FluSurv-NET identified 27 881 laboratory-confirmed, influenza-associated hospitalizations. Of these, 15 051 (54.0%) were among those aged 65 years or older, 15 246 (54.7%) were among female patients, 3169 (11.4%) were among Hispanic patients, 6165 (22.1%) were among non-Hispanic Black patients, 15 631 (56.1%) were among non-Hispanic White patients, and 2916 (10.5%) were among those included in the other race and ethnicity category. The cumulative lab-confirmed hospitalization rate of 80.0 per 100 000 people was the third highest cumulative rate at that time in the season since the 2010-2011 season. The majority of hospitalizations (25 698 hospitalizations [92.2%]) were associated with influenza A viruses; among 7512 influenza A hospitalizations with confirmed subtype, 6674 (88.8%) were A(H3N2). Across all age groups this season, adults aged 65 years and older had the highest cumulative influenza-associated hospitalization rate (261.5 per 100 000 persons), followed by children aged younger than 5 years (85.4 per 100 000 persons). Among children aged younger than 5 years, cumulative hospitalization rates were highest among infants aged younger than 1 year (131.7 per 100 000 persons).

Using rates from FluSurv-NET through March 14, 2026, we estimated that there have been between 28 000 000 to 49 000 000 illnesses, 360 000 to 740 000 hospitalizations, and 22 000 to 74 000 deaths associated with influenza infection in the US during the 2025-2026 season. As of March 14, 2026, the CDC classified the 2025-2026 in-season severity as moderate (Table 2).²³ When age-stratified, children had a high-severity season, while adults and older adults had a moderate-severity season. Concurrently, the Pediatric Influenza Mortality Surveillance System reported 115 pediatric influenza deaths through National Center for Health Statistics Mortality Surveillance Data. Based on preliminary FluSurv-NET data from March 19, 3808 of 4614 of hospitalized patients with influenza (82.5%) received antiviral treatment; treatment was lower among children aged 0 to 17 years (865 of 1258 patients [68.8%]) than for adults 18 years and older (ranging from 501 of 596 adults [84.1%] to 1847 of 2079 adults [88.8%]). Among FluSurv-NET hospitalizations, 1613 of 10 965 (14.7%) were admitted to the intensive care unit and 303 of 5231 (5.8%) were placed on mechanical ventilation.

Table 2. Influenza Seasonal Severity Assessment, US, September 28, 2025, Through March 14, 2026.

Age group, y	Percentage of influenza-like illness visits out of all outpatient visits, peak value	Classification	Adjusted hospitalization rate per 100 000 population, peak value	Classification	Percentage of influenza deaths out of all deaths, peak value	Classification	Preliminary 2025-2026 severity classification
0-17	16.5	High	8.5	High	3.4	Moderate	High
18-64	6.0	Moderate	11.1	Moderate	1.4	Moderate	Moderate
≥65	5.0	Very high	81.2	Moderate	2.1	Moderate	Moderate
All ages	8.3	High	21.1	Moderate	1.9	Moderate	Moderate

Estimated VE

From October 1, 2025, through March 4, 2026, VISION identified 135 029 emergency department or urgent care (ED/UC) encounters and 33 629 hospitalizations with acute respiratory illness. The median (IQR) age was 9 (5-13) years among children and 62 (39-76) years among adults. Among all ED/UC encounters and hospitalizations, 41 003 (24.3%) were among Hispanic patients, 17 797 (10.6%) were among non-Hispanic Black patients, 84 493 (50.1%) were among non-Hispanic White patients, 21 244 (12.6%) were among those included in the other race category, and 4121 (2.4%) were among those with unknown race. Among ED/UC encounters, 10 087 of 38 070 children (26.5%) and 17 925 of 96 959 adults (18.5%) tested positive for influenza A, and 596 children (1.6%) and 535 adults (0.6%) tested positive for influenza B. While 1961 of 10 671 children with influenza-positive results (18.4%) and 5061 of 18 448 adults with influenza-positive results (27.4%) in the ED/UC setting were vaccinated, 6476 of 27 399 children with influenza-negative results (23.6%) and 29 337 of 78 511 adults with influenza-negative results (37.4%) were vaccinated. Among hospitalizations, 128 of 1552 children (8.2%) and 2943 of 32 077 adults (9.2%) tested positive for influenza A, and 3 children (0.2%) and 33 adults (0.1%) tested positive for influenza B. While 30 of 131 children with influenza-positive results (22.9%) and 1209 of 2974 adults with influenza-positive results (40.7%) in the hospital setting were vaccinated, 446 of 1421 children with influenza-negative results (31.4%) and 12 544 of 29 103 adults with influenza-negative results (43.1%) were vaccinated.

Among persons of all ages, VE against any influenza virus was 35% (95% CI, 33%-38%) for influenza-associated ED/UC encounters and 27% (95% CI, 21%-34%) for influenza-associated hospitalizations (Table 3). VE against influenza A–associated ED/UC encounters was similar across age groups, ranging from 33% (95% CI, 30%-36%) to 37% (95% CI, 32%-41%). VE against influenza B–associated ED/UC encounters was 38% (95% CI, 23%-51%) among children and 63% (95% CI, 52%-72%) among adults. VE against influenza A–associated hospitalizations was 47% (95% CI, 14%-69%) among children and 26% (95% CI, 19%-33%) among adults. There were insufficient data to estimate VE against influenza B–associated hospitalizations.

Table 3. Influenza VE Against Influenza-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Children and Adults, US, October 1, 2025, Through March 4, 2026^a.

Age group and influenza type	Emergency department or urgent care encounters			Hospitalizations
	Influenza test result by influenza vaccination status, No. vaccinated/total No. (%)		VE (95% CI)b	Influenza test result by influenza vaccination status, No. vaccinated/total No. (%)		VE (95% CI)b
	Influenza-positive	Influenza-negative		Influenza-positive	Influenza-negative
All ages
Any influenza	7022/29 119 (24)	35 813/105 910 (34)	35 (33-38)	1239/3105 (40)	12 990/30 524 (43)	27 (21-34)
Children aged 6 mo-17 y
Any influenza	1961/10 671 (18)	6476/27 399 (24)	37 (33-41)	30/131 (23)	446/1421 (31)	47 (15-68)
Influenza A	1854/10 087 (18)	6476/27 399 (24)	37 (32-41)	29/128 (23)	446/1421 (31)	47 (14-69)
Influenza B	109/596 (18)	6476/27 399 (24)	38 (23-51)	NRc	NRc	NRc
Adults aged ≥18 y
Any influenza	5061/18 448 (27)	29 337/78 511 (37)	34 (31-37)	1209/2974 (41)	12 544/29 103 (43)	27 (20-33)
Influenza A	4987/17 925 (28)	29 337/78 511 (37)	33 (30-36)	1200/2943 (41)	12 544/29 103 (43)	26 (19-33)
Influenza B	78/535 (15)	29 337/78 511 (37)	63 (52-72)	NRc	NRc	NRc

Abbreviations: NR, not reported; VE, vaccine effectiveness.

^a VE estimates are preliminary and might change as additional data are received.

^b VE was estimated using the test-negative design comparing the odds of 2025-2026 influenza vaccination between influenza-positive cases and influenza-negative controls. Multivariable logistic regression was used to estimate the adjusted odds ratio (aOR) for the association of influenza vaccination with influenza-associated emergency department or urgent care encounters and hospitalizations, adjusting for age, sex, race and ethnicity, calendar time of illness, and study site. VE was estimated as (1 − aOR) × 100 and expressed as a percentage.

^c Data were not reported if there were fewer than 50 cases.

Discussion

This surveillance study found that US influenza surveillance data collected from September 28, 2025, to March 14, 2026, preliminarily meet the criteria to classify the 2025-2026 season as being of moderate severity for adults and high severity for children.²³ The most frequently identified viruses were subclade K viruses. VE estimates against any influenza in the ED/UC setting ranged from 34% to 37% among children and adults. These estimates were within the range of previous US VE estimates but are lower than VISION estimates in January 2025 for the 2024-2025 season and early 2025-2026 VE reported from England and Suzhou, Eastern China.^7,18,24 The predominant A(H3N2) viruses were antigenically drifted from the A(H3N2) vaccine component, and vaccine-induced immunity was reduced, which likely explains the lower VE.²¹

Similar to previous seasons, the 2025-2026 US influenza season started in early December 2025 when the rate of outpatient respiratory visits exceeded the baseline (ie, 3.1%).²⁵ Rates of laboratory-confirmed influenza hospitalization peaked in late December 2025, with peak weekly rates in children aged younger than 18 years and adults aged 18 to 29 years, higher than any season since 2010-2011. Except for the 2024-2025 season, the influenza-associated hospitalization rate for all ages during the peak week (13.2 per 100 000) was higher than peaks during all other seasons dating back to 2010-2011.²⁶ As of March 14, 2026, influenza activity remains elevated nationally but is decreasing in most of the country.

The influenza A(H3N2) subclade K viruses emerged after the February 2025 vaccine virus selection.^27,28 By mid-March 2026, 93% of US A(H3N2) viruses that the CDC genetically characterized were subclade K. Compared with the current A(H3N2) vaccine virus, subclade K hemagglutinins have alternate glycosylation patterns and amino acid differences in and near the receptor-binding domain and antibody binding sites.⁶ These changes are evidence of antigenic drift. Data indicate that vaccine-induced immunity to drifted viruses was reduced; however, among healthy pediatric and adults vaccinees who responded well to vaccination, vaccination still induced protective levels (≥40) of neutralizing antibodies against subclade K. One of the N-linked glycosylation changes in subclade K at HA position 135 (threonine to lysine) was present in A(H3N2) viruses that circulated during the US 2024-2025 season,²⁹ which could have provided some adults with preexisting immunity. CDC unpublished prospective population serosurveys suggests there is preexisting immunity in some age groups because of antibodies targeting shared epitopes between A(H3N2) subclade K and past A(H3N2) viruses.

Many people sought care in the US for influenza illnesses from December 2025 through March 2026. Almost 9 in 10 influenza-associated hospitalizations identified in FluSurv-NET with subtype information were A(H3N2) viruses. The cumulative influenza-associated hospitalization rate for this time was the third highest since the 2010-2011 season.²⁶ As with other seasons, during 2025-2026, older adults aged 65 years and older had the highest cumulative influenza hospitalization rates, followed by children younger than 5 years.²⁶ Such incidence, approximately 5 months into the 2025-2026 influenza season, correlates to the US already having experienced millions of influenza illnesses, hundreds of thousands of hospitalizations, and thousands of deaths.

Despite subclade K’s divergent antigenic characteristics, 2025-2026 Northern Hemisphere influenza vaccines did reduce the risk of serious illnesses.⁷ Data from the US VISION network, for example, indicates that seasonal influenza vaccination decreased the risk of needing ED and UC care for influenza-associated illnesses by approximately one-third. Influenza vaccination also decreased the risk of adult hospitalization by approximately one-quarter. Except for children, CDC US VE findings were similar to the VE estimates reported by Canada and England.⁷ From September to November 2025, subclade K predominated epidemic months in the UK, and vaccination with A/Croatia/10136RV/2023 (H3N2)–like or A/District of Columbia/27/2023 (H3N2)–like viruses decreased the risk of needing to seek influenza-associated emergency care by 34.8 to 74.8%, depending on age group. So far this season, our preliminary 2025-2026 VISION VE estimates for the US have been similar to past seasons when antigenically drifted A(H3N2) viruses predominated.^29,30

Influenza activity may continue through April 2026 in the Northern Hemisphere.³¹ When circulating influenza viruses are drifted from viruses represented in the seasonal influenza vaccines, vaccination can continue to protect against severe influenza illness, hospitalization, and death; protect against other circulating influenza viruses represented in the vaccines; and help reduce the overall community spread of influenza.³² While the emergence and spread of oseltamivir-resistant A(H1N1)pdm09 viruses with H275Y is an ongoing public health concern, which is monitored closely, influenza antivirals remain effective for treatment³³ against circulating viruses and are recommended for any patient with suspected or confirmed influenza who is hospitalized, has severe or complicated illness, or is at higher risk for influenza complications.^33,34 This information might be useful for Southern Hemisphere countries as they approach their 2026 season.

Limitations

This analysis of US data from the 2025-2026 season has several limitations. Influenza-positive surveillance specimens were submitted to the CDC in accordance with the Influenza Virologic Surveillance Right Size Roadmap⁹ and submission guidance³⁵ for virologic characterization to meet national goals for genetic surveillance, vaccine virus selection, and antiviral resistance detection. Viruses were selected for antigenic characterization based on genetic changes in their surface proteins, and the subset tested may not have been proportional to what was circulating. Participants in our vaccine immunogenicity studies might not be representative of all influenza vaccine recipients. Influenza hospitalizations from FluSurv-NET catchment covering 10% of the US population may not be representative of the entire country. Prior-season health seeking data were used to estimate multipliers to calculate the burden of influenza; year-to year-variability in health care seeking could affect estimates. VISION does not systematically conduct subtyping; we are therefore unable to provide VE estimates by influenza A subtype from this network. The data through March 2026 are preliminary and incidence, severity, burden, and VE estimates will change as data accrues.

Conclusions

In summary, the results of this surveillance study indicate the US is experiencing a moderate to high severity influenza season due to antigenically drifted influenza A(H3N2) viruses. These viruses were associated with expected high hospitalization rates in older people and higher rates in children. Influenza vaccination and treatment recommendations remain in effect while influenza continues to circulate. Influenza antiviral medications should be used to promptly treat patients with suspected or confirmed influenza who are hospitalized, have severe or complicated illnesses, or are at higher risk for influenza complications.

Supplement.

Data Sharing Statement