# Interim vaccine effectiveness against influenza virus among outpatients, France, October 2025 to January 2026

Allan de Clercq, François Blanquart, Vincent Vieillefond, Benoit Visseaux, Alexandra Jacques, Stéphanie Haim-Boukobza, Valentin Wehrle, Guillaume Deleglise, Thomas Duret, Sibylle Bernard-Stoecklin, et al.

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

Allan de Clercq, François Blanquart, Vincent Vieillefond, Benoit Visseaux, Alexandra Jacques, et al. Interim vaccine effectiveness against influenza virus among outpatients, France, October 2025 to January 2026. Eurosurveillance, 2026, 31 (2), pp.2500992. 10.2807/1560-7917.ES.2026.31.2.2500992. hal-05482003

HAL Id: hal-05482003

https://hal.science/hal-05482003v1

Submitted on 28 Jan 2026

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
# Interim vaccine effectiveness against influenza virus among outpatients, France, October 2025 to January 2026

Allan De Clercq¹,², François Blanquart³, Vincent Vieillefond⁴, Benoit Visseaux⁵, Alexandra Jacques⁶, Stéphanie Haim-Boukobza⁷, Valentin Wehrle⁸, Guillaume Deleglise⁹, Thomas Duret⁹, Sibylle Bernard-Stoecklin¹⁰, Danielle Perez-Bercoff¹¹, Antoine Oblette¹,¹², Bruno Lina¹,¹², Marie Anne Rameix-Welti¹¹,¹³, Laurence Josset¹,¹², Vincent Enouf¹¹, Antonin Bal¹,¹², on behalf of the RELAB study group¹⁴

1. Hospices Civils de Lyon (HCL), Centre National de Référence des virus des infections respiratoires, Institut des Agents Infectieux, Laboratoire de Virologie, Lyon, France

2. Université Lille, UFR3S - ILIS, Faculté d'Ingénierie et Management de la Santé, Lille, France

3. Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, France

4. BIOGROUP Paris Ouest, Levallois Perret, France

5. Département d'infectiologie, Laboratoire Cerba, Cerba Healthcare, Frépillon, France

6. Biogroup Lorraine, Grand Est, Metz, France

7. Laboratoires Cerballiance, Cerba Healthcare, Issy-les-Moulineaux, France

8. BioLBS, Lillebonne, France

9. INOVIE GEN-BIO, Clermont-Ferrand, France

10. Santé Publique France - Direction des maladies infectieuses, Saint-Maurice, France

11. National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumovirus, Institut Pasteur, Université Paris Cité, Paris, France

12. Centre International de Recherche en Infectiologie (CIRI), Laboratoire VirPath, Inserm U1111, de Lyon, Université Claude Bernard Lyon 1, Lyon, France

13. Molecular Mechanisms of Multiplication of Pneumovirus, Université Versailles St-Quentin en Yvelines, Paris-Saclay INSERM UMR 1173 (21), Assistance Publique des Hôpitaux de Paris, Paris, France

14. The members of the RELAB study group are listed under Acknowledgements

Correspondence: Antonin Bal (antonin.bal@chu-lyon.fr)

**Citation style for this article:**

De Clercq Allan, Blanquart François, Vieillefond Vincent, Visseaux Benoit, Jacques Alexandra, Haim-Boukobza Stéphanie, Wehrle Valentin, Deleglise Guillaume, Duret Thomas, Bernard-Stoecklin Sibylle, Perez-Bercoff Danielle, Oblette Antoine, Lina Bruno, Rameix-Welti Marie Anne, Josset Laurence, Enouf Vincent, Bal Antonin, on behalf of the RELAB study group. Interim vaccine effectiveness against influenza virus among outpatients, France, October 2025 to January 2026. Euro Surveill. 2026;31(2):pii=2500992. https://doi.org/10.2807/1560-7917.ES.2026.31.2.2500992.

Article received on 26 Dec 2025 / Accepted on 15 Jan 2026 / Published on 15 Jan 2026

In Europe, the 2025/26 seasonal influenza epidemic started in October 2025. Co-circulation of A(H3N2) and A(H1N1)pdm09 was observed in several countries including France. We estimated early vaccine effectiveness (VE) against influenza virus in French outpatients (5,451 positives/18,816 negatives). A significant VE across all age groups was measured: 28% (95% CI: 17–37) for those aged ≥ 65 years, 45% (95% CI: 36–53) for 18–64-year-olds and 57% (95% CIs: 29–74) for 0–17-year-olds. Reinforcing vaccination uptake is warranted.

Since October 2025, an early rise in influenza positivity rates has been observed across several European countries [1,2], particularly in England, which recorded its earliest influenza season since 2003/04 [3]. In France, the 2025/26 season is characterised by high circulation of influenza A(H3N2) viruses belonging to subclade K, with co-circulation of A(H1N1)pdm09 subclade D.3.1.1 [4]. Influenza positivity among patients tested in community laboratories increased as early as week 41/2025. In this context, we present an early assessment of influenza vaccine effectiveness (VE) against laboratory-confirmed influenza using

community laboratory surveillance data through week one of January 2026.

## Study population

Assessment of VE in community settings was conducted through the RELAB network, which included 1,600 community-based laboratories (BIOGROUP, BioLBS, Cerballiance and INOVIE GEN-BIO) across France [5]. Patients were tested for SARS-CoV-2, influenza virus and respiratory syncytial virus using triplex or quadruplex (influenza virus typing) RT-PCR. Additionally, data were collected on sex (female, male), age group (0–4, 5–17, 18–64, ≥ 65 years), PCR technique, week of testing and vaccination status (unvaccinated or prior vaccination from 15 days to 3 months before sampling).

The study population included patients tested between weeks 36/2025 and 1/2026 (1 September 2025–4 January 2026), totalling 98,900 individuals (n = 11,045 positives; 11.2%). All symptomatic patients were sampled within 5 days after symptom onset. Viral genomic sequencing was performed on a random subset of 526 samples positive for influenza virus up to week 50. We compared the current VE with end-of-season values

<figure><img src="image_3.png" /></figure>
TABLE

Characteristics of outpatients tested for influenza virus, France, November 2025–January 2026 (week 44/2025–1/2026), (n=24,267)

<table><thead><tr><th rowspan="2">Characteristic</th><th colspan="2">Negative (n=18,816)</th><th colspan="2">Positive (n=5,451)</th><th rowspan="2">p value<sup>a</sup></th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female</td><td>11,256</td><td>59.8</td><td>3,013</td><td>55.3</td><td rowspan="2">p&lt;0.001</td></tr><tr><td>Male</td><td>7,560</td><td>40.2</td><td>2,438</td><td>44.7</td></tr><tr><td>Age (years)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-4</td><td>1,208</td><td>6.4</td><td>605</td><td>11.1</td><td rowspan="4">p&lt;0.001</td></tr><tr><td>5-17</td><td>1,244</td><td>6.6</td><td>1,052</td><td>19.3</td></tr><tr><td>18-64</td><td>10,657</td><td>56.6</td><td>2,708</td><td>49.7</td></tr><tr><td>≥ 65</td><td>5,706</td><td>30.3</td><td>1,086</td><td>19.9</td></tr><tr><td>Vaccination against influenza virus<sup>b</sup></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No vaccination</td><td>15,683</td><td>83.3</td><td>4,750</td><td>87.1</td><td rowspan="2">p&lt;0.001</td></tr><tr><td>Vaccination 15 days-3 months</td><td>3,133</td><td>16.7</td><td>701</td><td>12.9</td></tr><tr><td>Fever (body temperature ≥ 38°C)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>8,685</td><td>46.2</td><td>4,174</td><td>76.6</td><td rowspan="3">p&lt;0.001</td></tr><tr><td>No</td><td>6,967</td><td>37.0</td><td>680</td><td>12.5</td></tr><tr><td>Missing</td><td>3,164</td><td>16.8</td><td>597</td><td>11.0</td></tr><tr><td>Respiratory symptoms</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>11,519</td><td>61.2</td><td>4,100</td><td>75.2</td><td rowspan="3">p&lt;0.001</td></tr><tr><td>No</td><td>4,917</td><td>26.1</td><td>755</td><td>13.9</td></tr><tr><td>Missing</td><td>2,380</td><td>12.6</td><td>596</td><td>10.9</td></tr><tr><td>Any symptom of influenza-like illness</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>14,048</td><td>74.7</td><td>4,944</td><td>90.7</td><td>p&lt;0.001</td></tr><tr><td>Week of testing</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>44/2025</td><td>1,772</td><td>9.4</td><td>61</td><td>1.1</td><td rowspan="11">p&lt;0.001</td></tr><tr><td>45/2025</td><td>1,966</td><td>10.4</td><td>80</td><td>1.5</td></tr><tr><td>46/2025</td><td>1,492</td><td>7.9</td><td>116</td><td>2.1</td></tr><tr><td>47/2025</td><td>1,622</td><td>8.6</td><td>143</td><td>2.6</td></tr><tr><td>48/2025</td><td>1,743</td><td>9.3</td><td>271</td><td>5.0</td></tr><tr><td>49/2025</td><td>2,098</td><td>11.2</td><td>695</td><td>12.7</td></tr><tr><td>50/2025</td><td>2,544</td><td>13.5</td><td>1,136</td><td>20.8</td></tr><tr><td>51/2025</td><td>2,576</td><td>13.7</td><td>1,371</td><td>25.2</td></tr><tr><td>52/2025</td><td>1,483</td><td>7.9</td><td>879</td><td>16.1</td></tr><tr><td>1/2026</td><td>1,520</td><td>8.1</td><td>699</td><td>12.8</td></tr></tbody></table>

obtained in the previous season 2024/25 of the RELAB network with the same methodology [6,7].

The VE assessment was restricted to patients tested after week 44/2025 (15 days after the start of the vaccination campaign in France) and for whom the required variables (age, sex, vaccination status, PCR technique, week of testing) were reported for the models, totaling 24,267 patients of which 78.3% were symptomatic (Table). Tests for influenza virus were positive for 5,451 (22.5%) patients. The large fraction of symptomatic patients reflects the most likely reason for virological PCR testing in France, which is presenting to a GP with fever or respiratory infection symptoms and being referred for a test.

## Vaccination campaign in France

Annual influenza vaccination is recommended for people at risk of severe disease (≥ 65 years, chronic conditions, pregnant people, severe obesity, residents of care facilities), children aged ≥ 6 months with comorbidities, healthcare workers, caregivers and close contacts of vulnerable individuals; it may also be offered to all children aged 2–17 years. Inactivated trivalent vaccines are used for the general eligible population. The composition of the vaccine for the northern hemisphere (NH) 2025/26 includes strains 5a.2a.1 subclade D for A(H1N1)pdm09, which remained unchanged from the 2023/24 season, 2a.3a.1 subclade J.2 for A(H3N2), and V1A.3a.2 for B/Victoria viruses [8]. In our population, 37.5% (2,544/6,792) of patients aged ≥ 65 years

<figure><img src="image_4.png" /></figure>

<footnote><sup>a</sup> Differences between negative and positive tests were tested with Pearson's chi-square test and considered significant at the <0.001 level.</footnote>

<footnote><sup>b</sup> Vaccination was self-reported.</footnote>
FIGURE 1

Comparison of weekly influenza test positivity across two seasons: early season 2025/26 (n=98,900) and 2024/25 season (n=202,820) (Panel A), influenza positivity stratified by age group (Panel B) and positivity for non-vaccinated individuals and those vaccinated 2025/26 (Panel C), France, September 2025–January 2026

<figure><img src="image_5.png" /></figure>

were vaccinated, as presented in Supplementary Table S1.

For adults aged ≥ 65 years, enhanced vaccines, high-dose and adjuvanted [9] formulations, are preferentially recommended to improve protection against severe outcomes. By week 48/2025, national vaccination coverage in this age group reached 44.2% [4]. Of those vaccinated, 30% received enhanced vaccines. It is noteworthy that enhanced vaccines were not available for the last season 2024/25.

## Epidemiology of an early season

Over the past two seasons, we monitored weekly test positivity rates and the number of influenza cases detected (Figure 1A). The influenza positivity rate increased 1–2 weeks earlier in 2025/26 than in the previous season. The positivity rate, at week 48, was 12.0% (512/4,258), compared with 8.2% (538/6,525) in the 2024/25 season. By week 52, the positivity rate had risen to 36.2% (1,702/4,701), compared with 35.8% (1,630/4,554) in the 2024/25 season. Although the positivity rate may in principle be a biased indicator of incidence [10], here it correlated strongly with the number of detected cases, as presented in Supplementary Figure S1. When stratified by age group (Figure 1B), influenza virus circulation was high among younger patients, especially among those aged 5–17 years (70% positivity rate at week 52). When vaccination status was reported, the positivity rate in the VE study population differed significantly between unvaccinated

and vaccinated individuals (Figure 1C) since week 47 (Wilson test, 95% confidence interval (CI)).

## Genetic diversity of influenza viruses

During the first weeks of the season (week 36–50), 526 samples positive for influenza virus from the RELAB network were sequenced, with A(H1N1)pdm09 being the most common (54.2%; n=285), followed by A(H3N2) (44.9%; n=236) and a low detection of B/Victoria viruses (n=3), with only the C.5.6 subclade identified (Figure 2A). Among the A(H1N1)pdm09 viruses, D.3.1.1 was the most common (n=244), with sporadic detections of D.3.1 and C.1.9.3. Among A(H3N2) viruses, subclade K was the most detected one (n=206), with sporadic detections of subclades J.2, J.2.2, J.2.3 and J.2.4. Influenza A(H3N2) subclade K is a genetically distinct branch of the A(H3N2) virus that has accumulated multiple haemagglutinin mutations relative to earlier circulating viruses, resulting in notable antigenic drift from the A(H3N2) NH vaccine strain [11].

When examining the weekly proportions (Figure 2B), A(H3N2) K subclade was the most commonly detected subclade, at 52.7% (174/330) of the sequenced viruses between weeks 44 and 50, while A(H1N1)pdm09 subclade D.3.1.1 was at 39.1% (129/330). At week 50, A(H3N2) subclade K was identified in 22 of 37 of the viruses sequenced.

<figure><img src="image_6.png" /></figure>
FIGURE 2

Temporal distribution and proportion of influenza virus subclades identified by sequencing, France, September 2025–December 2025 (n = 526)ᵃ,ᵇ

<figure><img src="image_7.png" /></figure>

Interim vaccine effectiveness against
influenza in the community †

We used a test-negative design and measured VE as (1-odds ratio (OR)) with 95% CIs, where OR represents the odds of vaccination among test-positive to the odds of vaccination among test-negative patients. The variables retained for the analysis were: age, sex, vaccination status, PCR technique and week of testing. We compared VE across different groups (overall, PCR-confirmed influenza A, stratified by age or symptom) and with the final estimates of the previous season estimated with the same methodology in the same network in 2024/25 (see Discussion) [6,7]. All VE estimates presented are adjusted estimates (Figure 3).

The overall interim VE estimate for individuals vaccinated from 15 days to 3 months before testing was 36.4% (95% CI: 29.7-42.5). Among the population aged ≥ 65years, the point estimate was lower, peaking at 27.7% and with an overlapping CI (95% CI: 16.7-37.3). Consistent with the genetic diversity of circulating viruses, the overall VE closely overlapped the VE influenza A PCR-typed detection, which was 36.8% (95% CI: 28.4-44.3). The vaccine might have been more effective in younger patients than in older adults but with overlapping CIs, (45.1 % for 18-64 years and 57.2% for 0-17 years).

Discussion

In contrast to the early influenza epidemiology in
England [3] which is dominated by the circulation of
A(H3N2) K subclade, the 2025/26 influenza season in
France has first been dominated by the A(H1N1)pdm09
subclade D.3.1.1. The A(H3N2) subclade K began to be
more common from week 49 in France according to our

sequencing data. Although we did not have sequenc-
ing data for weeks 51/2025, 52/2025 and 1/2026, data
on the subtyped samples from the Sentinelles network
of GPs report [12] suggest the frequency of subclade K
kept increasing. The interim VE assessment presented
here reflects the co-circulation of A(H1N1) D.3.1.1 and
A(H3N2) K subclades.

The interim 2025/26 VE estimated in the present study was similar to the end-of-season estimates assessed for the 2024/25 season [6,7], keeping in mind differences in epidemiological context, vaccination and testing strategies. During the 2024/25 season, the three seasonal influenza viruses, A(H1N1)pdm09, A(H3N2) and B/Victoria co-circulated [6,7], enhanced vaccines were not available for patients aged ≥ 65years, and a GP's prescription was not required for reimbursement. However, during the 2024/25 season, a prescription was reported for 79% of patients suggesting that the study population is largely similar for these two seasons. Depletion-of-susceptible biases and 'leaky' vaccine effect [13,14] could lead to a spurious waning of VE at the end of the season. However, we found no evidence of such biases, as the end-of-season estimates were comparable (and no lower) than those of the interim analysis from last season.

The 2025/26 interim point estimate for individuals aged
≥ 65years was slightly higher than last season with
28% (95% CI: 17–37) and 25% (95% CI: 18–32), respec-
tively. Seasonal differences in VE may reflect variations
in type/subtype distribution, availability of enhanced
vaccines, repeated vaccination with the same A(H1N1)
pdm09 strain from 2023/24 [8,15,16], population pre-
season immunity and birth cohort effects [17]. Further

<figure><img src="image_8.png" /></figure>

<footnote>ᵃ Sequences from week 50 not consolidated.</footnote>

<footnote>ᵇ Vertical bars represent the VE assessment period.</footnote>
FIGURE 3

Interim adjusted vaccine effectiveness against influenza by cumulative week (from week 42), overall and stratified by age and PCR-detected influenza A virus, France, October 2025–January 2026, compared across two seasons

<table><thead><tr><th></th><th>Cases (n)</th><th>Vaccinated (%)</th><th>Unvaccinated (%)</th><th>Controls (n)</th><th>Vaccinated (%)</th><th>Unvaccinated (%)</th><th></th><th></th><th>VE% (95% CI)</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Interim (week 44/2025-1/2026)<sup>a</sup></td><td>5,451</td><td>701 (12.9%)</td><td>4,750 (87.1%)</td><td>18,816</td><td>3,133 (16.7%)</td><td>15,683 (83.3%)</td><td>—</td><td>—</td><td>36.42 (29.67-42.52)</td></tr><tr><td>End-of-season estimate 2024/25<sup>b</sup></td><td>20,650</td><td>2,024 (9.8%)</td><td>18,626 (90.2%)</td><td>57,054</td><td>10,517 (18.4%)</td><td>46,537 (81.6%)</td><td>—</td><td>—</td><td>44.50 (41.20-47.60)</td></tr><tr><td><strong>Symptoms<sup>a,c</sup></strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Any symptom (week 44/2025-1/2026)</td><td>4,944</td><td>632 (12.8%)</td><td>4,312 (87.2%)</td><td>18,816</td><td>3,133 (16.7%)</td><td>15,683 (83.3%)</td><td>—</td><td>—</td><td>33.64 (26.26-40.28)</td></tr><tr><td>Respiratory symptom (week 44/2025-1/2026)</td><td>4,100</td><td>562 (13.7%)</td><td>3,538 (86.3%)</td><td>18,816</td><td>3,133 (16.7%)</td><td>15,683 (83.3%)</td><td>—</td><td>—</td><td>30.22 (22.04-37.54)</td></tr><tr><td>Fever symptom (week 44/2025-1/2026)</td><td>4,174</td><td>471 (11.3%)</td><td>3,703 (88.7%)</td><td>18,816</td><td>3,133 (16.7%)</td><td>15,683 (83.3%)</td><td>—</td><td>—</td><td>37.07 (29.23-44.04)</td></tr><tr><td><strong>Influenza A</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Interim (week 44/2025-1/2026)<sup>d</sup></td><td>3,558</td><td>454 (12.8%)</td><td>3,104 (87.2%)</td><td>18,816</td><td>3,133 (16.7%)</td><td>15,683 (83.3%)</td><td>—</td><td>—</td><td>36.84 (28.36-44.31)</td></tr><tr><td>End-of-season estimate 2024/25<sup>b</sup></td><td>7,967</td><td>1,085 (13.6%)</td><td>6,882 (86.4%)</td><td>57,054</td><td>10,517 (18.4%)</td><td>46,537 (81.6%)</td><td>—</td><td>—</td><td>32.10 (26.50-37.30)</td></tr><tr><td><strong>Age ≥ 65 years</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Interim (week 44/2025-1/2026)<sup>e</sup></td><td>1,086</td><td>460 (42.4%)</td><td>626 (57.6%)</td><td>5,706</td><td>2,084 (36.5%)</td><td>3,622 (63.5%)</td><td>—</td><td>—</td><td>27.74 (16.68-37.34)</td></tr><tr><td>End-of-season estimate 2024/25<sup>b</sup></td><td>2,542</td><td>1,188 (46.7%)</td><td>1,354 (53.3%)</td><td>14,944</td><td>6,749 (45.2%)</td><td>8,195 (54.8%)</td><td>—</td><td>—</td><td>25.10 (18.20-31.50)</td></tr><tr><td><strong>Age 18-64 years<sup>e</sup></strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Interim (week 44/2025-1/2026)</td><td>2,708</td><td>218 (8.1%)</td><td>2,490 (91.9%)</td><td>10,657</td><td>990 (9.3%)</td><td>9,667 (90.7%)</td><td>—</td><td>—</td><td>45.05 (35.64-53.08)</td></tr><tr><td><strong>Age 0-17 years<sup>e</sup></strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Interim (week 44/2025-1/2026)</td><td>1,657</td><td>23 (1.4%)</td><td>1,634 (98.6%)</td><td>2,452</td><td>59 (2.4%)</td><td>2,393 (97.6%)</td><td>—</td><td>—</td><td>57.18 (29.45-74.01)</td></tr></tbody></table>

analysis of VE by variant and vaccine type is warranted. Of note, we did not compare estimates for other age groups, as vaccination recommendations did not target these groups.

When comparing these present estimates with the preliminary inpatient estimates from England (where A(H3N2) subclade K is predominant) [3], the VE for the patients aged ≥ 65 years reported herein (28%) was similar to the VE for emergency department visits at 35% (95% CI: 22–45) and lower than the VE for hospital admissions, which was 39% (95% CI: 26–50), suggesting a higher protection against hospitalisation. Our overall VE estimate (36%) fitted in the 95% CI of the the early pooled European estimate (44%; 95% CI: 25–59), despite differences in subtyped distribution (mainly A(H3N2) at 75%) and the population [18]. Specifically, the European analysis included 8% of cases among individuals aged ≥ 65 years, which was insufficient to estimate VE, compared with 28% in our study. Despite the increasing circulation of subclade K viruses in Europe, preliminary results presented herein and also from England [3], do not suggest a reduction in VE compared with the southern hemisphere (SH) 2025 estimates [19], where A(H1N1)pdm09 predominated [2]. The VE SH interim result for influenza-like illness patients (outpatient settings) was 45% (95% CI: 24–60) which overlapped with our estimates [19].

Although considering ongoing epidemiological trends, the increase in prevalence of influenza A(N3N2) subclade K viruses could extend the season, as observed in Australia and New Zealand [20]. In this scenario, the epidemic in France might continue to increase in incidence in early 2026 and peak at a high level because of infections with different subtypes. These observations warrant further investigations to assess the long-term impact of subclade K viruses.

As in our previous analyses, our methods are subject to limitations: selection bias (test-seeking behaviour), health status confounding (“healthy person bias” and “indication confounding”), difficulty in extrapolating our findings to more severe outcomes, such as hospitalisation and mortality rates, and recall bias due to self-reporting of vaccination and symptoms. However, symptomatic patients were examined by a GP in order to obtain a prescription for the test. For the majority of the population, vaccination occurred from 15 days and 3 months before testing, which highlights the need to reassess the VE at the end of the season to determine whether waning immunity has occurred. Compared with the previous season, an additional limit was introduced because both standard and enhanced vaccines were available but data on the type of vaccine administered was missing. However, our estimates for the 2023/24 season [21], which align closely with the

<figure><img src="image_9.png" /></figure>

<footnote>a GLM with a binomial response for PCR-detected infection, adjusted for categorical variables including sex (female, male), age group (18–64, 0–4, 5–17, ≥ 65 years), PCR technique, week of testing and vaccination status (unvaccinated, prior vaccination from 15 days to 3 months).</footnote>

<footnote>b Adjusted vaccine effectiveness (adjusted for categorical variables including sex (female, male), age group (18–64, 0–4, 5–17, ≥ 65 years), PCR technique, week of testing and vaccination status (unvaccinated, prior vaccination within from 15 days to 3 months)) for the 2024/25 season, assessed using the same methodology and network as previously published [7].</footnote>

<footnote>c Stratification by symptoms: fever (body temperature ≥ 38°C) or respiratory symptoms.</footnote>

<footnote>d GLM with a binomial response for PCR-typed influenza A virus, adjusted for categorical variables including sex (female, male), age group (18–64, 0–4, 5–17, ≥ 65 years), PCR technique, week of testing and vaccination status (unvaccinated, prior vaccination from 15 days to 3 months).</footnote>

<footnote>e GLM with a binomial response for PCR-detected infection, adjusted for categorical variables including sex (female, male), PCR technique, week of testing and vaccination status (unvaccinated, prior vaccination from 15 days to 3 months).</footnote>
pooled VE reported in a meta-analysis of 108 studies [22], indicate that in spite of these limitations, our data and methods give meaningful estimates of VE.

## Conclusion

Despite a partial vaccine mismatch this season, interim analyses indicate a statistically significant vaccine effectiveness across all age groups. In the context of sustained influenza circulation in Europe, reinforcing vaccination uptake in the coming weeks is strongly recommended.

## †Author's correction

In the article, there was an error in the following sentence: "We used a test-negative design and measured VE as (1- odds ratio (OR)) with 95% CIs, where OR represents the OR of vaccination among test-positive to the OR of vaccination among test-negative patients". The term OR in the latter parts of the sentence should be replaced by the term odds. The sentence was corrected on 20 January 2026 at the request of the authors.

## Data availability

All RELAB sequences are available on GISAID.

## Authors' contributions

Allan De Clercq: Conceptualisation, Formal analysis, Methodology, Visualisation, Writing – original draft. François Blanquart: Formal analysis, Writing – original draft. Vincent Vieillefond: Data curation, Methodology. Benoit Visseaux: Data curation, Methodology. Alexandra Jacques: Data curation, Methodology. Stéphanie Haim-Boukobza: Data curation, Methodology. Valentin Wehrle: Data curation, Methodology. Guillaume Deleglise: Data curation, Methodology. Thomas Duret: Data curation, Methodology. Sibylle Bernard-Stoecklin: Data curation, Methodology. Danielle Perez Bercoff: Data curation, Methodology. Antoine Oblette: Data curation, Methodology. Bruno Lina: Data curation, Methodology. Marie Anne Rameix-Welti: Data curation, Methodology. Laurence Josset: Data curation, Methodology. Vincent Enouf: Data curation, Methodology. Antonin Bal: Conceptualisation, Data curation, Methodology, Supervision, Writing – original draft.

## Conflict of interest

None declared.

## Funding statement

Not applicable.

## Ethical statement

The study protocol received approval from the institutional review board of the Hospices Civils de Lyon (Comité Scientifique et Éthique des Hospices Civils de Lyon) in June 2023 (reference 23-5039). All patients or the parents of minors were provided with an information notice explaining the nature and purpose of the collected data. In cases where a patient or parent objected to data usage, the corresponding data was excluded from the research database. To ensure

confidentiality, unique anonymised alphanumeric identifiers were assigned, and data transfers to the research team were conducted via a secure portal, accessible exclusively to authorised research personnel.

## Use of artificial intelligence tools

None declared.

## Acknowledgements

We would like to acknowledge all members of RELAB laboratories.
Members of the RELAB study group: Valentin Wehrle (bioLBS), Guillaume Deleglise (INOVIE), Thomas Duret (INOVIE) Arnaud François (Bioesterel, Biogroup PACA); Alexandre Vignola (Oriade Noviale, Biogroup AURA); Vincent Garcia (Alphabio, Biogroup PACA); Alexandra Jacques (Biogroup Lorraine, Grand Est); Jonas Amzalag (Biolam, Biogroup IDF); Nadège Gourgouillon (CAB Biogroup, Grand Est); Remi Labetoulle (Laborizon, Biogroup Nouvelle Aquitaine); Frederique Roumanet (Unilians, Biogroup AURA); Arthur Denoel (Laborizon, Biogroup Bretagne); Hilel Mehamha (CBM25, Biogroup Bourgogne Franche-Comté); Thierry Guffond (Diagnovie, Biogroup Hauts de France); Magali HYPOLITE (2A2B, Biogroup Corse); Yanis Chaib (Biolam, Biogroup IDF); Timothée Goetschy (Biogroup national, équipe Data); Elodie Ostermann (Biogroup national, équipe Data); Anne Holstein (Laborizon Biogroup Centre Val de Loire); Vincent Vieillefond (BPO-Bioépine Biogroup IDF); Jean Marc Giannoli (Biogroup national); Julienne de Pontcharra (Bioesterel, Biogroup PACA); Jean Francois Comes (Laborizon, Biogroup Bretagne); Justine Gasnot (Bioesterel, Biogroup PACA); Theo Corbet (Unilians, Biogroup AURA); Laurent Kbaier (Bioesterel, Biogroup PACA); Emmanuel Chanard (Cerballiance, Auvergne Rhône Alpes); Arcadie Gioud (Cerba Xpert, Auvergne Rhône Alpes); Stéphanie Arsene (Cerballiance, Normandie Bocage); Maxime Sansot (Cerballiance, Pays de Loire); Anne-Lise Gautier (Cerballiance, Portes de Bretagne); Kariach Goldar (Cerballiance, Martinique); Mahery Ramiandrisoa (Cerballiance, Réunion); Aristide Nzeumi (Cerballiance, Réunion); Pauline Jestin (Cerballiance, Charentes); Gilles Abs (Cerballiance, Centre Val-de-Loire); Guillemette Wandler (Cerballiance, Centre Valde-Loire); Anne-Claire Strzelecki (Cerballiance, Occitanie); Sarah Cerdan (Cerballiance, Occitanie); Edouard Delaunay (Cerballiance, Alpes Durance); Sandrine Barrieu-Moussat (Cerballiance, Côte d'azur); Laurence Prots (Cerballiance, Côte d'azur); Edouard Delaunay (Cerballiance, Provence); Johanna Roux (Cerballiance, Ile-de-France Est); Yasmina De Saint Salvy (Cerballiance, Ile-de-France Est); Agnes Durand (Cerballiance, Ile-de-France Est); Aude Lesenne (Cerballiance, Ile-de-France Sud); Kader Merah (Cerballiance, Ile-de-France Sud); Erwan Le Naour (Cerballiance, Aquitaine Nord); David Robert (Cerballiance, Aquitaine Nord); Sophie Zaffreya (Cerballiance, Aquitaine Nord); Jean-Philippe Galhaud (Cerballiance, Aquitaine Sud); Claire Felloni (Cerballiance, Artois); Dominique Dyda (Cerballiance, Haut-de-France); Aurelie Dupuis (Cerballiance, Bretagne); Gwenole Prigent (Cerballiance, Bretagne); Stephanie Arsene (Cerballiance, Normandie Ouest); Antoine Prigent (Cerballiance, Normandie Ouest); Natacha Tatoyan (Cerballiance, Nouvelle Calédonie); Benoit Visseaux (Laboratoire Cerba, Pole Infectiologie); Bénédicte Roquebert (Laboratoire Cerba, Pole Infectiologie); Stéphanie Haim-Boukobza (Cerba Healthcare); Odile Rousselet (Cerba Healthcare) and Michel Sala (Cerba Healthcare).

## References

1. European Centre for Disease Prevention and Control (ECDC) and World Health Organization Regional Office for Europe. (WHO/

<figure><img src="image_10.png" /></figure>
Europe). European Respiratory Virus Surveillance Summary (ERVISS). Stockholm: ECDC and Copenhagen: WHO/Europe; 2026. Available from: https://erviss.org/

2. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017;22(13):30494. https://doi.org/10.2807/1560-7917. ES.2017.22.13.30494 PMID: 28382917

3. Kirsebom FC, Thompson C, Talts T, Kele B, Whitaker HJ, Andrews N, et al. Early influenza virus characterisation and vaccine effectiveness in England in autumn 2025, a period dominated by influenza A(H3N2) subclade K. Euro Surveill. 2025;30(46):2500854. https://doi.org/10.2807/1560-7917. ES.2025.30.46.2500854 PMID: 41267661

4. Santé publique France (SPF). Infections respiratoires aiguës (grippe, bronchiolite, COVID-19). Bulletin du 24 décembre 2025. [Acute respiratory infections (influenza, bronchiolitis, COVID-19). Bulletin 24 December 2025]. Saint-Maurice: SPF; 24 Dec 2025. French. Available from: https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/grippe/documents/bulletin-national/infections-respiratoires-aigues-grippe-bronchiolite-covid-19-. bulletin-du-24-decembre-2025

5. Traore A, Charniga K, Grellet S, Terpant G, Da Cruz H, Lamy A, et al. Monitoring SARS-CoV-2 variants with complementary surveillance systems: risk evaluation of the Omicron JN.1 variant in France, August 2023 to January 2024. Euro Surveill. 2025;30(1):2400293. https://doi.org/10.2807/1560-7917. ES.2025.30.1.2400293 PMID: 39790077

6. Blanquart F, Vieillefond V, Visseaux B, Abou Chakra CN, Nunes MC, Jacques A, et al. Influenza vaccine effectiveness against detected infection in the community, France, October 2024 to February 2025. Euro Surveill. 2025;30(7):2500074. https:// doi.org/10.2807/1560-7917.ES.2025.30.7.2500074 PMID: 39980426

7. Clercq A, Blanquart F, Vieillefond V, Visseaux B, Chakra CNA, Nunes MC, et al. Influenza vaccine effectiveness and genetic diversity: insights from end-of-season community surveillance, France, 2024-2025. Emerg Microbes Infect. 2025;14(1):2562045. https://doi.org/10.1080/22221751.2025.2562045 PMID: 40955037

8. World Health Organization (WHO). Recommended composition of influenza virus vaccines for use in the 2025-2026 northern hemisphere influenza season. Geneva: WHO; 28 Feb 2025. Available from: https://cdn.who.int/media/docs/ default-source/influenza/who-influenza-recommendations/ vcm-northern-hemisphere-recommendation-2025-2026/ recommended-composition-of-influenza-virus-vaccines-for- use-in-the-2025-2026-northern-hemisphere-influenza-season. pdf?sfvrsn=857c2e9b_13&download=true

9. Haute Autorité de Santé (HAS). Grippe saisonnière : la HAS précise la place des vaccins Efluelda et Fluad dans la stratégie vaccinale. [Seasonal influenza: the HAS clarifies the role of the Efluelda and Fluad vaccines in the vaccination strategy]. Saint-Denis: HAS; 9 May 2025. French. Available from: https:// www.has-sante.fr/jcms/p_3604208/fr/grippe-saisonniere-la- has-precise-la-place-des-vaccins-efluelda-et-fluad-dans-la- strategie-vaccinale

10. Eales O, McCaw JM, Shearer FM. Biases in routine influenza surveillance indicators used to monitor infection incidence and recommendations for improvement. Influenza Other Respir Viruses. 2024;18(12):e70050. https://doi.org/10.1111/irv.70050 PMID: 39617738

11. Zambon M, Hayden FG. Influenza A(H3N2) subclade K virus: threat and response. JAMA. 2025. https://doi.org/10.1001/ jama.2025.25903 PMID: 41411120

12. Réseau Sentinelles (Sentinelles). Bulletin de surveillance épidémiologique pour la semaine 1 de l'année 2026, du 29/12/25 au 04/01/26. [Epidemiological surveillance bulletin for week 1 of the year 2026, from 29/12/25 to 04/01/26]. Paris: Sentinelles; 7 Jan 2026. French. Available from: https:// sentiweb.fr/

13. Lipsitch M. Challenges of vaccine effectiveness and waning studies. Clin Infect Dis. 2019;68(10):1631-3. https://doi. org/10.1093/cid/ciy773 PMID: 30204853

14. Ray GT, Lewis N, Klein NP, Daley MF, Lipsitch M, Fireman B. Depletion-of-susceptibles bias in analyses of intra-season waning of influenza vaccine effectiveness. Clin Infect Dis. 2020;70(7):1484-6. https://doi.org/10.1093/cid/ciz706 PMID: 31351439

15. World Health Organization (WHO). Recommendations announced for influenza vaccine composition for the 2024-2025 northern hemisphere influenza season. Geneva: WHO; 23 Feb 2024. Available from: https://www.who.int/news/ item/23-02-2024-recommendations-announced-for-influenza- vaccine-composition-for-the-2024-2025-northern-hemisphere- influenza-season

16. World Health Organization (WHO). Recommendations announced for influenza vaccine composition for the 2023-2024 northern hemisphere influenza season. Geneva: WHO; 24 Feb 2023. Available from: https://www.who.int/news/ item/24-02-2023-recommendations-announced-for-influenza- vaccine-composition-for-the-2023-2024-northern-hemisphere- influenza-season

17. Kissling E, Maurel M, Pozo F, Pérez-Gimeno G, Buda S, Sève N, et al. Influenza vaccine effectiveness in Europe and the birth cohort effect against influenza A(H1N1)pdm09: VEBIS primary care multicentre study, 2023/24. Euro Surveill. 2025;30(23):2500011. https://doi.org/10.2807/1560-7917. ES.2025.30.23.2500011 PMID: 40511473

18. European Centre for Disease Prevention and Control (ECDC). Early estimates of seasonal influenza vaccine effectiveness against influenza requiring medical attention at primary care level in Europe, week 41 - 49, 2025. 2025. Stockholm: ECDC; 19 Dec 2025. Available from: https://www.ecdc.europa.eu/ en/news-events/early-estimates-seasonal-influenza-vaccine- effectiveness-against-influenza-requiring

19. Russ S, Nogareda F, Regan AK, Benedetti E, Pasinovich M, Voto C, et al. Interim effectiveness estimates of 2025 southern hemisphere influenza vaccines in preventing influenza-associated outpatient and hospitalized illness - eight southern hemisphere countries, March-September 2025. MMWR Morb Mortal Wkly Rep. 2025;74(36):570-8. https://doi.org/10.15585/ mmwr.mm7436a3 PMID: 40996960

20. Dapat C, Peck H, Jelley L, Diefenbach-Elstob T, Slater T, Hussain S, et al. Extended influenza seasons in Australia and New Zealand in 2025 due to the emergence of influenza A(H3N2) subclade K viruses. Euro Surveill. 2025;30(49):2500894. https://doi.org/10.2807/1560-7917.ES.2025.30.49.2500894 PMID: 41383175

21. Abou Chakra CN, Blanquart F, Vieillefond V, Enouf V, Visseaux B, Haim-Boukobza S, et al. Vaccine effectiveness dynamics against influenza and SARS-CoV-2 in community-tested patients in France 2023-2024. Emerg Microbes Infect. 2025;14(1):2466699. https://doi.org/10.1080/22221751.2025.2 466699 PMID: 40071892

22. Scott J, Abers MS, Marwah HK, McCann NC, Meyerowitz EA, Richterman A, et al. Updated evidence for Covid-19, RSV, and influenza vaccines for 2025-2026. N Engl J Med. 2025;393(22):2221-42. https://doi.org/10.1056/ NEJMsa2514268 PMID: 41160817

License, supplementary material and copyright

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence and indicate if changes were made.

Any supplementary material referenced in the article can be
found in the online version.

This article is copyright of the authors or their affiliated in-
stitutions, 2026.

<figure><img src="image_11.png" /></figure>