1887
  1. Home
  2. Eurosurveillance
  3. Volume 30, Issue 5, 06/Feb/2025
  4. Article
Research Open Access
Like 0
Download

Abstract

Background

Respiratory syncytial virus (RSV) causes substantial morbidity in infants < 1 year. In October 2023, Spain recommended the monoclonal antibody nirsevimab to all children born since 1 April 2023, at birth or as catch-up if born before October 2023.

Aim

We estimated nirsevimab effectiveness in preventing RSV hospitalisations during the 2023/24 season.

Methods

We conducted a nationwide population-based matched case–control study. Cases were children hospitalised for lower respiratory tract infection who were RSV PCR-positive. For each case, we selected four population density controls born in the same province and date (±2 days). We defined at-birth immunisation as receiving nirsevimab during the first 2 weeks of life, and catch-up immunisation within 30 days from campaign onset. Causal intention-to-treat (ITT) and per-protocol (PP) effectiveness was estimated using inverse-probability-of-immunisation weighted conditional logistic regression.

Results

We included 406 cases and 1,623 controls in catch-up and 546 cases and 2,182 controls in at-birth immunisation studies. Effectiveness in preventing RSV hospitalisations for catch-up immunisation was 71% (95% confidence interval (CI): 65–76) by ITT and 80% (95% CI: 75–84) PP. Effectiveness for at-birth immunisation was 78% (95% CI: 73–82) by ITT and 83% (95% CI: 79–87) PP. Effectiveness was similar for ICU admission, need of mechanical ventilation, and RSV viral subgroups A and B. Children born pre-term or with birthweight < 2,500 g showed lower PP effectiveness of 60–70%.

Conclusions

Population-level nirsevimab immunoprophylaxis in children in their first RSV season was very effective in preventing RSV hospitalisations, ICU admission and mechanical ventilation, with reduced but still high effectiveness for pre-term and low-birthweight children.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2025.30.5.2400596
2025-02-06
2025-02-08
/content/10.2807/1560-7917.ES.2025.30.5.2400596
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/30/5/eurosurv-30-5-3.html?itemId=/content/10.2807/1560-7917.ES.2025.30.5.2400596&mimeType=html&fmt=ahah

References

  1. Shi T, McAllister DA, O’Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017;390(10098):946-58.  https://doi.org/10.1016/S0140-6736(17)30938-8  PMID: 28689664 
  2. Wildenbeest JG, Billard MN, Zuurbier RP, Korsten K, Langedijk AC, van de Ven PM, et al. The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study. Lancet Respir Med. 2023;11(4):341-53.  https://doi.org/10.1016/S2213-2600(22)00414-3  PMID: 36372082 
  3. Del Riccio M, Spreeuwenberg P, Osei-Yeboah R, Johannesen CK, Fernandez LV, Teirlinck AC, et al. Burden of respiratory syncytial virus in the European Union: estimation of RSV-associated hospitalizations in children under 5 years. J Infect Dis. 2023;228(11):1528-38.  https://doi.org/10.1093/infdis/jiad188  PMID: 37246724 
  4. Beyfortus | European Medicines Agency [Internet] [Internet]. [cited 2023 Dec 23]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/beyfortus
  5. Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med. 2017;9(388):1928.  https://doi.org/10.1126/scitranslmed.aaj1928  PMID: 28469033 
  6. Wilkins D, Yuan Y, Chang Y, Aksyuk AA, Núñez BS, Wählby-Hamrén U, et al. Durability of neutralizing RSV antibodies following nirsevimab administration and elicitation of the natural immune response to RSV infection in infants. Nat Med. 2023;29(5):1172-9.  https://doi.org/10.1038/s41591-023-02316-5  PMID: 37095249 
  7. Ponencia de Programa y Registro de Vacunaciones. Comisión de Salud Pública del Consejo Interterritorial del Sistema Nacional de Salud. Recomendaciones de utilización de nirsevimab frente a virus respiratorio sincitial para la temporada 2023-2024 [Recomendations for the use of nirsevimab against the respiratory syncytial virus for the 2023-2024 season in Spain]. Madrid, July 2023. [Internet]. Available from: https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab_2023.pdf
  8. Ponencia de Programa y Registro de Vacunaciones. Comisión de Salud Pública del Consejo Interterritorial del Sistema Nacional de Salud. Recomendaciones de utilización de nirsevimab para la temporada 2024-2025 en España [Recomendations for the use of nirsevimab in the 2024-2025 season in Spain]. Madrid, March 2024. Available at: [Internet]. [cited 2024 Jun 21]. Available from: https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab.pdf
  9. Rose S, van der Laan MJ. A targeted maximum likelihood estimator for two-stage designs. Int J Biostat. 2011;7(1):17.  https://doi.org/10.2202/1557-4679.1217  PMID: 21556285 
  10. Hernán MA, Sauer BC, Hernández-Díaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016;79:70-5.  https://doi.org/10.1016/j.jclinepi.2016.04.014  PMID: 27237061 
  11. Robins JM, Hernán MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11(5):550-60.  https://doi.org/10.1097/00001648-200009000-00011  PMID: 10955408 
  12. Greenland S. Variance estimators for attributable fraction estimates consistent in both large strata and sparse data. Stat Med. 1987;6(6):701-8.  https://doi.org/10.1002/sim.4780060607  PMID: 2825320 
  13. Muller WJ, Madhi SA, Seoane Nuñez B, Baca Cots M, Bosheva M, Dagan R, et al. Nirsevimab for prevention of RSV in term and late-preterm infants. N Engl J Med. 2023;388(16):1533-4.  https://doi.org/10.1056/NEJMc2214773  PMID: 37018470 
  14. Haerskjold A, Kristensen K, Kamper-Jørgensen M, Nybo Andersen AM, Ravn H, Graff Stensballe L. Risk factors for hospitalization for respiratory syncytial virus infection: a population-based cohort study of Danish children. Pediatr Infect Dis J. 2016;35(1):61-5.  https://doi.org/10.1097/INF.0000000000000924  PMID: 26398871 
  15. Nagayama Y, Tsubaki T, Nakayama S, Sawada K, Taguchi K, Tateno N, et al. Gender analysis in acute bronchiolitis due to respiratory syncytial virus. Pediatr Allergy Immunol. 2006;17(1):29-36.  https://doi.org/10.1111/j.1399-3038.2005.00339.x  PMID: 16426252 
  16. Regis E, Fontanella S, Lin L, Howard R, Haider S, Curtin JA, et al. Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study. Sci Rep. 2021;11(1):23741.  https://doi.org/10.1038/s41598-021-03044-x  PMID: 34887467 
  17. Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010;10(5):338-49.  https://doi.org/10.1016/S1473-3099(10)70049-9  PMID: 20417416 
  18. Simões EAF, Madhi SA, Muller WJ, Atanasova V, Bosheva M, Cabañas F, et al. Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials. Lancet Child Adolesc Health. 2023;7(3):180-9.  https://doi.org/10.1016/S2352-4642(22)00321-2  PMID: 36634694 
  19. Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020;383(5):415-25.  https://doi.org/10.1056/NEJMoa1913556  PMID: 32726528 
  20. Drysdale SB, Cathie K, Flamein F, Knuf M, Collins AM, Hill HC, et al. Nirsevimab for prevention of hospitalizations due to RSV in infants. N Engl J Med. 2023;389(26):2425-35.  https://doi.org/10.1056/NEJMoa2309189  PMID: 38157500 
  21. Coma E, Martinez-Marcos M, Hermosilla E, Mendioroz J, Reñé A, Fina F, et al. Effectiveness of nirsevimab immunoprophylaxis against respiratory syncytial virus-related outcomes in hospital and primary care settings: a retrospective cohort study in infants in Catalonia (Spain). Arch Dis Child. 2024;109(9):736-41.  https://doi.org/10.1136/archdischild-2024-327153  PMID: 38857952 
  22. López-Lacort M, Muñoz-Quiles C, Mira-Iglesias A, López-Labrador FX, Mengual-Chuliá B, Fernández-García C, et al. Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024. Euro Surveill. 2024;29(6):2400046.  https://doi.org/10.2807/1560-7917.ES.2024.29.6.2400046  PMID: 38333937 
  23. Ezpeleta G, Navascués A, Viguria N, Herranz-Aguirre M, Juan Belloc SE, Gimeno Ballester J, et al. Effectiveness of nirsevimab immunoprophylaxis administered at birth to prevent infant hospitalisation for respiratory syncytial virus infection: a population-based cohort study. Vaccines (Basel). 2024;12(4):383.  https://doi.org/10.3390/vaccines12040383  PMID: 38675765 
  24. Ares-Gómez S, Mallah N, Santiago-Pérez MI, Pardo-Seco J, Pérez-Martínez O, Otero-Barrós MT, et al. Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study. Lancet Infect Dis. 2024;24(8):817-28.  https://doi.org/10.1016/S1473-3099(24)00215-9  PMID: 38701823 
  25. Lund LC, Støvring H, Pottegård A, Andersen M, Hallas J. Cox regression using a calendar time scale was unbiased in simulations of COVID-19 vaccine effectiveness & safety. J Clin Epidemiol. 2023;156:127-36.  https://doi.org/10.1016/j.jclinepi.2023.02.012  PMID: 36806733 
  26. Robins J, Hernan M. Estimation of the causal effects of time-varying exposure. In: Longitudinal Data Analysis.2008. p. 553-99.
  27. Moline HL, Tannis A, Toepfer AP, Williams JV, Boom JA, Englund JA, et al. Early estimate of nirsevimab effectiveness for prevention of respiratory syncytial virus-associated hospitalization among infants entering their first respiratory syncytial virus season - New Vaccine Surveillance Network, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024;73(9):209-14.  https://doi.org/10.15585/mmwr.mm7309a4  PMID: 38457312 
  28. Assad Z, Romain AS, Aupiais C, Shum M, Schrimpf C, Lorrot M, et al. Nirsevimab and hospitalization for RSV bronchiolitis. N Engl J Med. 2024;391(2):144-54.  https://doi.org/10.1056/NEJMoa2314885  PMID: 38986058 
  29. Paireau J, Durand C, Raimbault S, Cazaubon J, Mortamet G, Viriot D, et al. Nirsevimab effectiveness against cases of respiratory syncytial virus bronchiolitis hospitalised in paediatric intensive care units in France, September 2023-January 2024. Influenza Other Respir Viruses. 2024;18(6):e13311.  https://doi.org/10.1111/irv.13311  PMID: 38840301 
  30. Li G, Gerlovin H, Figueroa Muñiz MJ, Wise JK, Madenci AL, Robins JM, et al. Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness. Epidemiology. 2024;35(2):137-49.  https://doi.org/10.1097/EDE.0000000000001709  PMID: 38109485 
Effectiveness of catch-up and at-birth nirsevimab immunisation against RSV hospital admission in the first year of life: a population-based case–control study, Spain, 2023/24 season
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Olivier+N%C3%BA%C3%B1ez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Núñez Olivier</a>, <a href="/search?value1=Carmen+Olmedo&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Olmedo Carmen</a>, <a href="/search?value1=David+Moreno-Perez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Moreno-Perez David</a>, <a href="/search?value1=Nicola+Lorusso&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lorusso Nicola</a>, <a href="/search?value1=Sergio+Fern%C3%A1ndez+Mart%C3%ADnez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fernández Martínez Sergio</a>, <a href="/search?value1=Pedro+Eliseo+Pastor+Villalba&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pastor Villalba Pedro Eliseo</a>, <a href="/search?value1=%C3%81ngeles+Gutierrez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Gutierrez Ángeles</a>, <a href="/search?value1=Marcos+Alonso+Garcia&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Alonso Garcia Marcos</a>, <a href="/search?value1=Pello+Latasa&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Latasa Pello</a>, <a href="/search?value1=Rosa+Sancho&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Sancho Rosa</a>, <a href="/search?value1=Jacobo+Mendioroz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Mendioroz Jacobo</a>, <a href="/search?value1=Montserrat+Martinez-Marcos&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Martinez-Marcos Montserrat</a>, <a href="/search?value1=Enriqueta+Mu%C3%B1oz+Plat%C3%B3n&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Muñoz Platón Enriqueta</a>, <a href="/search?value1=Mar%C3%ADa+Victoria+Garc%C3%ADa+Rivera&option1=author&noRedirect=true" class="nonDisambigAuthorLink">García Rivera María Victoria</a>, <a href="/search?value1=Olaia+P%C3%A9rez-Martinez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pérez-Martinez Olaia</a>, <a href="/search?value1=Rosa+%C3%81lvarez-Gil&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Álvarez-Gil Rosa</a>, <a href="/search?value1=Eva+Rivas+Wagner&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rivas Wagner Eva</a>, <a href="/search?value1=Nieves+L%C3%B3pez+Gonzalez-Coviella&option1=author&noRedirect=true" class="nonDisambigAuthorLink">López Gonzalez-Coviella Nieves</a>, <a href="/search?value1=Matilde+Zornoza&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Zornoza Matilde</a>, <a href="/search?value1=M+Isabel+Barranco&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Barranco M Isabel</a>, <a href="/search?value1=M+del+Carmen+Pacheco&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pacheco M del Carmen</a>, <a href="/search?value1=Virginia+%C3%81lvarez+R%C3%ADo&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Álvarez Río Virginia</a>, <a href="/search?value1=Miguel+Fiol+Jaume&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fiol Jaume Miguel</a>, <a href="/search?value1=Roxana+Morey+Arance&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Morey Arance Roxana</a>, <a href="/search?value1=Bego%C3%B1a+Adiego+Sancho&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Adiego Sancho Begoña</a>, <a href="/search?value1=Manuel+Mendez+Diaz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Mendez Diaz Manuel</a>, <a href="/search?value1=Noa+Batalla&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Batalla Noa</a>, <a href="/search?value1=Cristina+Andreu&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Andreu Cristina</a>, <a href="/search?value1=Jes%C3%BAs+Castilla&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Castilla Jesús</a>, <a href="/search?value1=Manuel+Garc%C3%ADa+Cenoz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">García Cenoz Manuel</a>, <a href="/search?value1=Ana+Fern%C3%A1ndez+Ib%C3%A1%C3%B1ez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fernández Ibáñez Ana</a>, <a href="/search?value1=Marta+Huerta+Huerta&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Huerta Huerta Marta</a>, <a href="/search?value1=Ana+Carmen+Ib%C3%A1%C3%B1ez+P%C3%A9rez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ibáñez Pérez Ana Carmen</a>, <a href="/search?value1=Bel%C3%A9n+Berradre+S%C3%A1enz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Berradre Sáenz Belén</a>, <a href="/search?value1=Joaqu%C3%ADn+Lamas&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lamas Joaquín</a>, <a href="/search?value1=Luisa+Hermoso&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hermoso Luisa</a>, <a href="/search?value1=Susana+Casado+Cobo&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Casado Cobo Susana</a>, <a href="/search?value1=Manuel+Gal%C3%A1n+Cuesta&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Galán Cuesta Manuel</a>, <a href="/search?value1=Sara+Montenegro&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Montenegro Sara</a>, <a href="/search?value1=Mar%C3%ADa+Dom%C3%ADnguez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Domínguez María</a>, <a href="/search?value1=Inmaculada+Jarr%C3%ADn&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Jarrín Inmaculada</a>, <a href="/search?value1=Aurora+Limia&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Limia Aurora</a>, <a href="/search?value1=Roberto+Pastor-Barriuso&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pastor-Barriuso Roberto</a>, <a href="/search?value1=Susana+Monge&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Monge Susana</a>, <a href="/search?value1=the+Nirsevimab+Effectiveness+Study+Collaborators&option1=author&noRedirect=true" class="nonDisambigAuthorLink">the Nirsevimab Effectiveness Study Collaborators</a></span>. Effectiveness of catch-up and at-birth nirsevimab immunisation against RSV hospital admission in the first year of life: a population-based case–control study, Spain, 2023/24 season. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(5):pii=2400596. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.5.2400596" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.5.2400596</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 10 Sept 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 17 Dec 2024 </span> </p>
/content/10.2807/1560-7917.ES.2025.30.5.2400596
/content/10.2807/1560-7917.ES.2025.30.5.2400596
Loading

Data & Media loading...

Supplementary data

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error