Effectiveness of nirsevimab against hospitalisation for RSV-bronchiolitis during high RSV-B circulation in the second year of nationwide implementation in France: a test-negative case-control study

Apolline Furgier^{1

2

3}, Camille Brehin^{4

5}, Corinne Levy^{4

6

7

8}, Romain Basmaci^{3

4

9}, Elise Launay^{4

10}, Camille Jung¹¹, Zein Assad^{2

3

4}, Léa Lenglart^{3

12}, Jérome Naudin¹³, Anne-Lise Mary¹³, Camille Aupiais¹⁴, Loïc de Pontual^{4

14}, Valérie Biran¹⁵, Béatrice Boutillier¹⁵, Isabelle Hau¹⁶, Mickael Shum¹⁶, Sandra Biscardi¹⁶, Céline Delestrain¹⁶, Julie Toubiana^{4

17}, Jérémie F Cohen^{4

17}, Amélie Lambert-Hoffert¹⁷, Mathie Lorrot^{4

18}, Anne-Sophie Romain¹⁸, Marion Ashman¹⁸, Jee-Seon Yang¹⁸, Blandine Prevost¹⁸, Harriet Corvol^{4

19}, Clément Basse²⁰, François Dubos^{4

20}, Marie Cotillon⁹, Constance Bridonneau¹⁰, Lise-Martin Perceval¹⁰, Etienne Bizot²¹, Inès Fafi^{3

22}, Aurélie Portefaix²³, Léa Domitien²³, Carine Jaillet²³, Antoine Ouziel²³, Luigi Titomanlio¹², Stephane Bechet^{6

8}, Vincent Gajdos²¹, Christèle Gras-Le Guen^{4

10}, Yves Gillet^{4

24

25}, Robert Cohen^{4

5

6

7

8}, Eric Jeziorski^{4

23}, Naim Ouldali^{1

2

3

4}; French Paediatric OVNI Network

Collaborators, Affiliations

Collaborators

Affiliations

¹ University of Paris Cite, Paris, France.
² AP-HP, Department of General Pediatrics, Pediatric Infectious Disease, and Internal Medicine, Robert Debre Hospital, Paris, France.
³ Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM UMR 1137, Paris Cité University, 75018, Paris, France.
⁴ French Paediatric Infectious Disease Group (GPIP), Nice, 06200, France.
⁵ Paediatric Infectious Diseases Department, Children's Hospital, Toulouse University Hospital, Toulouse, France.
⁶ Association Clinique et Therapeutique Infantile du Val-de-Marne France (ACTIV), France.
⁷ Association Française de Pédiatrie Ambulatoire (AFPA), Paris, France.
⁸ Université Paris Est, IMRB-GRC GEMINI, Créteil, France.
⁹ Paediatric Emergency Department and General Pediatrics Department, Louis Mourier University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité Université, Colombes, France.
¹⁰ Paediatric Emergency Department and General Pediatrics Department Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 5, Nantes, 44000, France.
¹¹ Délégation de Recherche en Santé et Innovation University Paris Est Créteil, Créteil, France.
¹² Paediatric Emergency Department, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, Paris, France.
¹³ Paediatric Intensive Care Unit, Robert-Debré University Hospital, AP-HP, Paris, France.
¹⁴ Sorbonne Paris Nord University, Assistance Publique-Hôpitaux de Paris, Paediatric Emergency Department and Department of General Paediatrics, Jean Verdier University Hospital, Bondy, France.
¹⁵ Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Robert Debre Hospital, Paris, France.
¹⁶ General Pediatrics Department, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁷ Necker Hospital for Sick Children, General Pediatrics and Pediatric Infectious Diseases, University of Paris Cité, Paris, France.
¹⁸ Department of General Pediatrics, Hôpital Armand-Trousseau, APHP, Université Paris Sorbonne, Paris, France.
¹⁹ Sorbonne University, Inserm U938, Saint-Antoine Research Center (CRSA), Assistance Publique - Hôpitaux de Paris (AP-HP), Trousseau Hospital, Paediatric Pulmonology Department, GRC SoLID, Paris, 75012, France.
²⁰ Paediatric Emergency Unit and Infectious Diseases, Centre Hospitalier Universitaire Lille, Université de Lille, Lille, France.
²¹ Paediatric Emergency Department and Department of General Paediatrics, Antoine-Béclère Hospital-Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Clamart, France.
²² Center of Clinical Investigations, INSERM CIC 1426, Robert-Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, 75019, France.
²³ Department of General Pediatrics, Infectiology, and Clinical Immunology, Department of Emergency, Post-Emergency Department, University Hospital of Montpellier, Montpellier, France.
²⁴ Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Paediatric Intensive Care and Emergency Department, Bron, France.
²⁵ KIDLIT Kids' Lyon Infectious Disease Team, Lyon, France.

PMID: 41220615
PMCID: PMC12598395
DOI: 10.1016/j.lanepe.2025.101443

Effectiveness of nirsevimab against hospitalisation for RSV-bronchiolitis during high RSV-B circulation in the second year of nationwide implementation in France: a test-negative case-control study

Apolline Furgier et al. Lancet Reg Health Eur. 2025.

. 2025 Sep 10:58:101443.

doi: 10.1016/j.lanepe.2025.101443. eCollection 2025 Nov.

Authors

Collaborators

Affiliations

¹ University of Paris Cite, Paris, France.
² AP-HP, Department of General Pediatrics, Pediatric Infectious Disease, and Internal Medicine, Robert Debre Hospital, Paris, France.
³ Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM UMR 1137, Paris Cité University, 75018, Paris, France.
⁴ French Paediatric Infectious Disease Group (GPIP), Nice, 06200, France.
⁵ Paediatric Infectious Diseases Department, Children's Hospital, Toulouse University Hospital, Toulouse, France.
⁶ Association Clinique et Therapeutique Infantile du Val-de-Marne France (ACTIV), France.
⁷ Association Française de Pédiatrie Ambulatoire (AFPA), Paris, France.
⁸ Université Paris Est, IMRB-GRC GEMINI, Créteil, France.
⁹ Paediatric Emergency Department and General Pediatrics Department, Louis Mourier University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité Université, Colombes, France.
¹⁰ Paediatric Emergency Department and General Pediatrics Department Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 5, Nantes, 44000, France.
¹¹ Délégation de Recherche en Santé et Innovation University Paris Est Créteil, Créteil, France.
¹² Paediatric Emergency Department, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, Paris, France.
¹³ Paediatric Intensive Care Unit, Robert-Debré University Hospital, AP-HP, Paris, France.
¹⁴ Sorbonne Paris Nord University, Assistance Publique-Hôpitaux de Paris, Paediatric Emergency Department and Department of General Paediatrics, Jean Verdier University Hospital, Bondy, France.
¹⁵ Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Robert Debre Hospital, Paris, France.
¹⁶ General Pediatrics Department, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁷ Necker Hospital for Sick Children, General Pediatrics and Pediatric Infectious Diseases, University of Paris Cité, Paris, France.
¹⁸ Department of General Pediatrics, Hôpital Armand-Trousseau, APHP, Université Paris Sorbonne, Paris, France.
¹⁹ Sorbonne University, Inserm U938, Saint-Antoine Research Center (CRSA), Assistance Publique - Hôpitaux de Paris (AP-HP), Trousseau Hospital, Paediatric Pulmonology Department, GRC SoLID, Paris, 75012, France.
²⁰ Paediatric Emergency Unit and Infectious Diseases, Centre Hospitalier Universitaire Lille, Université de Lille, Lille, France.
²¹ Paediatric Emergency Department and Department of General Paediatrics, Antoine-Béclère Hospital-Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Clamart, France.
²² Center of Clinical Investigations, INSERM CIC 1426, Robert-Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, 75019, France.
²³ Department of General Pediatrics, Infectiology, and Clinical Immunology, Department of Emergency, Post-Emergency Department, University Hospital of Montpellier, Montpellier, France.
²⁴ Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Paediatric Intensive Care and Emergency Department, Bron, France.
²⁵ KIDLIT Kids' Lyon Infectious Disease Team, Lyon, France.

PMID: 41220615
PMCID: PMC12598395
DOI: 10.1016/j.lanepe.2025.101443

Abstract

Background: Nirsevimab was first introduced in September 2023, showing strong real-world effectiveness in preventing hospitalised RSV-bronchiolitis. RSV-A circulation predominated during 2023-2024, whereas RSV-B was frequent in 2024-2025. Recent reports indicated resistance to nirsevimab in RSV-B strains in France. We aimed to assess the effectiveness of large-scale nirsevimab implementation against hospitalised RSV-bronchiolitis during high RSV-B circulation.

Methods: A test-negative case-control study was conducted using a national hospital-based surveillance system. All children <12 months hospitalised for bronchiolitis and tested for RSV in 12 French hospitals from October 10, 2024 to March 15, 2025, were included. Cases were RSV-positive bronchiolitis; controls were RSV-negative bronchiolitis. Effectiveness was assessed by a multivariable logistic regression model adjusted for confounders (sex, gestational age at birth, birth weight, risk factors for severe bronchiolitis, month of diagnosis, and medical centre). A range of sensitivity analyses was conducted.

Findings: 1270 patients were included; among which 830 (65.3%) were RSV-positive and 440 (34.7%) were RSV-negative bronchiolitis. The male-to-female sex ratio was 1.35, and the median age was 3 months (IQR: 1.5-5.6). Among cases, 182 (22.0%) received nirsevimab, compared to 282 (64.1%) for controls. Adjusted effectiveness against RSV-bronchiolitis was 84.9% (95% CI, 80.0-88.6). Subgroup analyses by age and severity (intensive care unit admission, respiratory support) showed consistent results, along with sensitivity analyses.

Interpretation: Despite high RSV-B circulation, which has recently been identified to carry mutations potentially inducing resistance to nirsevimab, the effectiveness of the second national nirsevimab campaign against hospitalisation for RSV-bronchiolitis remained high.

Funding: The study received financial support from Sanofi, AstraZeneca, and the 2023 ATIP-Avenir grant from the National Institute of Health and Medical Research (Inserm).

Keywords: Effectiveness; Nirsevimab; Paediatrics; RSV-bronchiolitis; Test-negative study.

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Conflict of interest statement

RB declares receiving fees from Sanofi and MSD for medical conferences or scientific meetings. CL declares receiving travel grants from MSD, Pfizer and fees from Sanofi, GSK, MSD, and Pfizer for scientific meetings and expert board participation. RC reports personal fees and non-financial support from Pfizer and personal fees from Cerballiance, GSK, Merck, Pfizer, Sanofi, Viatris outside the submitted work. NO declares receiving travel grants from MSD, Pfizer, Sanofi, and GSK. VG declares receiving fees from Sanofi and MSD for medical conferences and expert group. EL declares receiving travel grants from GSK and fees for medical conference from MSD. EJ declares receiving travel grants from Sanofi, GRIFOLS, MSD and fees from Sanofi, LFB, GSK, Pfizer for scientific meetings and expert board participation. IH declares receiving grants drop Pfizer, Sanofi, and MSD, and consulting fees from Cerballiance and payment for symposiums from GSK. FD déclares receiving travel Grant from MSD and being board member for Sanofi and MSD. All other authors have no conflicts of interest to disclose.

Figures

**Fig. 1**
**Flowchart of study participants.** Abbreviation: RSV = respiratory syncytial virus.

**Fig. 2**
**Effectiveness of nirsevimab for hospitalised bronchiolitis.** Case and control patients are infants with bronchiolitis hospitalised with respectively an upper way test positive for RSV or negative. n/N (%) represents the number of infants immunised with nirsevimab divided by the total number of case or control patients. Effectiveness were calculated using the following formula: (1 − adjusted odds ratio) × 100. Multiple imputation was used for all sensitivity analysis, except for the complete cases model. All the details of the differences analysis are detailed in Table S1 in Supplementary Appendix. Multivariate logistic regression model was adjusted for age (in month), prematurity (yes/no), birth weight (in kilogrammes), risk factor of severe bronchiolitis (including congenital heart disease, bronchopulmonary dysplasia, or a gestational age <35 weeks for infants under 6 months (yes/no)), month of bronchiolitis diagnosis, and the participating centre. Abbreviation: CI = confidence interval.

See this image and copyright information in PMC

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Effectiveness of nirsevimab against hospitalisation for RSV-bronchiolitis during high RSV-B circulation in the second year of nationwide implementation in France: a test-negative case-control study

Collaborators

Affiliations

Effectiveness of nirsevimab against hospitalisation for RSV-bronchiolitis during high RSV-B circulation in the second year of nationwide implementation in France: a test-negative case-control study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

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