Position Paper in Support of Protecting All Newborns Against Complications Associated with Respiratory Syncytial Virus (RSV) Infection

The Need to Protect All Newborns Against RSV

Respiratory syncytial virus (RSV) represents a major public health issue, with significant impact on all children, especially newborns and infants, regardless of whether they are born during or outside of the epidemic season. RSV is one of the most contagious respiratory viruses, with an infectivity index of 4.5 [1–4]. Consequently, approximately 70% of infants become infected with RSV during their first year of life, and nearly all children (90%) will contract the virus by the age of two [5].

Epidemiological data show that RSV can infect all children, regardless of birth timing: half of hospitalized infants are born before the epidemic season, and the other half are born during the epidemic season and still have an immature immune system [4–6]. Both groups are vulnerable to severe forms of RSV infection. According to statistical data:

• RSV is responsible for 50–80% of bronchiolitis cases [7] and 31% of infant pneumonias [8];

• Approximately 40% of first RSV infections progress to lower respiratory tract infections (LRTIs) [9];

• The average annual hospitalization rate is 19.4 per 1000 infants under 1 year old, meaning about 1 in 50 infants is hospitalized during the first year of life due to RSV infection [10];

•  RSV accounts for 1 in 5 acute respiratory tract infections requiring outpatient medical care [11];

• RSV infection increases the risk of asthma by 25%, in addition to the increased risk of recurrent wheezing and reduced lung function [12].

An analysis published in The Journal of Infectious Diseases (2023) indicates that Romania ranks 6th in Europe for RSV hospitalizations in infants <1 year old and remains among the top countries in the <5-year-old group, with an incidence far above the European average [13].

In the absence of a specific antiviral, RSV infection management is limited to symptomatic, pathogenic, and supportive treatment, thus making prophylaxis the only effective intervention to reduce the disease burden in infants.

In this context, RSV infection prophylaxis has become essential through the currently available options, namely:

1. Passive Immunization of the Newborn (Monoclonal Antibodies)

• Conventional or classical monoclonal antibodies (e.g., palivizumab): a monoclonal antibody authorized for high-risk infants (premature, with bronchopulmonary dysplasia or congenital heart disease), requiring monthly administration for five consecutive months during the RSV circulation season;

• Long-acting monoclonal antibodies (e.g., nirsevimab): a long-acting monoclonal antibody administered as a single dose, currently the only available RSV prevention solution suitable for all infants on a large scale.

Monoclonal antibodies represent one of the main innovative solutions in preventing viral infections in newborns and infants by providing immediate passive immunity. One of the key advantages of monoclonal antibodies is the immediate protection offered to the newborn from the moment of administration.

Another major advantage is long-term protection for all newborns, both those born during the RSV season and those born outside the epidemic period.

Phase II and III clinical trials have shown that the use of long-acting monoclonal antibodies significantly reduces the risk of hospitalization due to severe RSV infections by up to 86.0% at 150 days [14].

Subsequent real-world evidence (from clinical practice) has shown that long-acting monoclonal antibodies significantly reduce the risk of hospitalization due to severe RSV infections. For example, a systematic review and meta-analysis showed that nirsevimab reduced RSV-related hospitalization risk by 83% (OR: 0.19; 95% CI: 0.12–0.29) [15].

Additionally, nirsevimab reduces the risk of intensive care unit admission (OR: 0.19; 95% CI: 0.12–0.29) and the incidence of LRTIs (OR: 0.25; 95% CI: 0.19–0.33) [15]. After the first season of implementing nirsevimab prophylaxis in Galicia (September 2023–March 2024), a reduction of 89.8% (IQR 87.5–90.3) in RSV-related LRTI hospitalizations was observed [16].

In Chile, within the 2024 national universal immunization campaign with nirsevimab, monitored through the NIRSE-CL project, a 77.46% reduction in RSV-associated hospitalizations was estimated [17].

2. Active Immunization of Pregnant Women (RSV preF Vaccination)

The recombinant RSV preF vaccine, approved for use during pregnancy, protects infants against RSV through transplacental transfer of neutralizing antibodies produced in the mother. A single dose is administered to pregnant women between 24–36 weeks of gestation. In the phase III study, the RSV preF recombinant vaccine showed 82.4% efficacy (95% CI, 57.5–93.9) in preventing severe RSV-associated LRTIs requiring medical care in infants within the first 90 days of life, and 70.0% (95% CI, 50.6–82.5) within the first 180 days [18].

Final Considerations

Real-world data support the effectiveness of immunization strategies against RSV. Passive immunization with long-acting monoclonal antibodies has been associated with an 80–90% reduction in hospitalizations in the USA [19], Spain [20], and France [21], in contexts where over 80% of eligible infants received the intervention. Simultaneously, maternal vaccination with RSV preF showed 78.6% effectiveness in Argentina against RSV-associated LRTI hospitalizations within the first 3 months of life and 71.3% effectiveness up to 6 months of age, in a context with a maternal vaccination coverage rate of 62.5%, confirming clinical trial results [22].

Long-acting monoclonal antibodies are thus effective in reducing the disease burden at the population level and represent a valuable public health intervention, with the potential to protect all infants regardless of their risk status and to sustainably complement existing prophylaxis efforts.

Conclusions

The Romanian Society of Preventive Medicine, the Romanian Association for Pediatric Education in Family Medicine, the Romanian National Society of Pediatric Infectious Diseases, and the Society of Infectious Diseases and HIV/AIDS, referring to the above:

• Support the adoption of evidence-based preventive measures aimed at reducing the impact of RSV infection in newborns and infants;

• Recommend the implementation of modern, effective, and scientifically supported interventions to protect children's health by preventing RSV-related respiratory complications and reducing the risk of hospitalization;

• Consider it essential to protect all newborns, regardless of birth timing relative to the RSV season, through prophylactic interventions tailored to both the individual and epidemiological context;

• Emphasize the importance of complementing available active immunization options (vaccination) with modern passive immunization options in national prophylaxis programs, as an integral part of a comprehensive strategy to protect the health of newborns and infants against severe RSV forms;

• Recommend the adoption of an integrated and effective strategy to prevent RSV infection, enabling the implementation of appropriate prophylactic measures for each individual, such as:

  • Passive infant immunization via maternal RSV vaccination (a single dose administered to pregnant women between 24 and 36 weeks of gestation, anytime during the year) or

  • Passive immunization of the newborn and infant through administration of monoclonal antibodies:

    • For high-risk infants (prematurity, congenital heart disease, bronchopulmonary dysplasia): use of an authorized monoclonal antibody, administered monthly over a 5-month period corresponding to the epidemic season;

    • For all infants and newborns: universal immunization with long-acting monoclonal antibodies providing full-season RSV protection with a single dose.

It is imperative to ensure access to available prophylactic options, as well as continuous medical education in the field of prophylaxis, so that healthcare professionals can make informed decisions when choosing the recommended strategy for each patient.

References

1. Heylen E, et al. Biochem Pharmacol. 2017,127:1-12.
2. Carvajal JJ, et al. Front Immunol. 2019,10:2152.
3. Reis J, et al. Infect Dis Mod. 2018:3:23-34.
4. Drajac C, et al. J Immunol Res. 2017;2017:8734504.
5. Reeves RM, et al. J Infect. 2019;78:468-475.
6. Tregoning JS, Schwarze J. Clin Microbiol Rev. 2010:23:74-98.
7. Meissner HC. N Engl J Med. 2016;374:62-72.
8. Mazur NI, et al. Lancet Infect Dis. 2023:23:e2-e21.
9. Esposito S, et al. Front Immunol. 2022:13:880368.
10. McLaughlin JM, et al. J Infect Dis. 2020.jiaa752.
11. Lively JY, et al. J Pediatric Infect Dis Soc. 2019;8:284-286.
12. Rosas-Salazar C, Chirkova T, et al. Lancet, 2023;401(:1669-1680.
13. Del Riccio M. et al. J Infect Dis. 2023:228:1528-1538.
14. Simões EAF, et al. Lancet Child Adolesc Health. 2023:7:180-189.
15. Sumsuzzman D, et al. Lancet Child Adolesc Health 2025; 9: 393-403
16. Ares-Gómez S, et al. Lancet Infect Dis. 2024;24:817-828.
17. Torres JP, Sauré D, Goic M, Thraves C, Pacheco J, Burgos J, et al. Lancet Infect Dis. 2025 10:S1473-309900233-693.
18. Simðes EAF, et al. Obstet Gynecol. 2025;145:157-167.
19. Hsiao A, et al. Presented at ACAAI Annual Scientific Meeting 2024, Boston, MA.
20. Agüera M, et al. Pediatr Allergy Immunol. 2024;35:e14175.
21. Assad Z, et al. N Engl J Med. 2024;391:144-54.
22. Pérez Marc G, et al. Lancet Infect Dis. 2025:S1473-3099(25)00156-2.