RSV in Infants and Young Children: Are You Taking It Seriously Enough?

Respiratory syncytial virus (RSV) is a major global cause of acute lower respiratory tract infections in infants and young children, resulting in significant morbidity and mortality. While often presenting with mild, cold-like symptoms in older children and adults, RSV infection can escalate to a serious lower respiratory tract infection (LRTI), such as bronchiolitis or pneumonia, in infants. It is one of the leading causes of infant hospitalization in the United States. Worldwide, it accounts for up to 190,000-350,000 hospitalizations and 10,000-23.000 pediatric deaths each year, disproportionately affecting infants aged <6 months.^1,2

Beyond acute illness, RSV disease in early life has been associated with long-term respiratory complications, including recurrent wheezing and asthma, as well as increased antibiotic use due to development of secondary bacterial infections.³ The substantial clinical burden translates into a major economic impact: The U.S. healthcare burden from RSV in pediatric and adult populations exceeds $7 billion annually in direct and indirect costs.^2,4 Pediatric hospitalizations alone contribute to over 40% of the total RSV-related hospitalization costs, largely driven by the intensive care needs associated with severe bronchiolitis and pneumonia.⁴

RSV-related lower respiratory tract infections in infants are influenced by multiple factors including young age, prematurity, and underlying conditions like congenital heart and lung disease or immune disorders, all of which increase risk. Environmental factors—crowding, smoke exposure, pollution, and poverty—further contribute to more severe courses of illness.  While prior traditional prophylaxis programs targeted only high-risk infants—those born prematurely or with chronic lung or congenital heart disease—population data reveal that the majority of severe RSV cases occur in full-term, otherwise healthy infants. Importantly, 80% of infants with severe RSV disease in high-income countries have no underlying medical condition, emphasizing the need for universal prophylaxis.⁵

The American Academy of Pediatrics (AAP) advises RSV immunization for the following groups:

• Infants younger than 8 months who are born during or are about to enter their first RSV season should receive immunoprophylaxis if:

• • The pregnant parent did not receive the maternal RSVpreF vaccine during the current pregnancy,

• • The pregnant parent’s RSV vaccination status is unknown, or

• • The infant was born within 14 days of the pregnant parent’s RSVpreF vaccination.

• Children aged 8 to 19 months who are at elevated risk for severe RSV disease and are entering their second RSV season should also be immunized with nirsevimab, regardless of maternal RSV vaccination status or previous receipt of nirsevimab or clesrovimab during infancy.

High-risk conditions include:

• • American Indian or Alaska Nativechildren, due to significantly higher rates of severe disease and hospitalization associated with social drivers of health

• • Severe immunocompromise

• • Chronic lung disease of prematurity requiring medical management (such as corticosteroids, diuretics, or supplemental oxygen) within the prior 6 months

• • Cystic fibrosis with either:

• • • Documented severe lung involvement (eg, prior hospitalization for pulmonary exacerbation or persistent abnormalities on chest imaging), or

• • • Weight-for-length below the 10th percentile

Seasonality and the Mandate for Timely Immunoprophylaxis
RSV disease circulation typically follows a seasonal pattern, with yearly epidemics that usually occur during the late fall, winter, and early spring months in temperate climates. In most of the continental United States, the RSV season typically runs from October through March. However, the timing of onset, peak, and decline of RSV activity varies geographically. For instance, RSV epidemics generally begin earlier in the Southeast and occur later in northern and western regions. In jurisdictions where seasonality deviates from the continental US average, such as Alaska or tropical climates, providers should rely on local public health guidance for optimal timing of intervention. ⁶

Available RSV Vaccines and Their Mechanism of Action
Current prophylactic strategies to prevent RSV disease in infants and children fall into two primary categories: maternal immunization, involving vaccinating the mother during pregnancy, and long-acting monoclonal antibodies, featuring the direct administration of monoclonal antibodies to the infant or child.

• Maternal Immunization: The bivalent RSV prefusion F (RSVpreF) vaccine is the only RSV vaccine approved for use during pregnancy in the United States. Maternal immunization allows for passive transplacental transfer of neutralizing antibodies, offering protection to infants during the early postnatal period when the risk of severe RSV disease is greatest. In the pivotal phase 3 MATISSE trial, vaccination between 24-36 weeks’ gestation reduced the risk of severe, medically-attended, RSV-associated LRTI by 81.8% within 90 days after birth and by 69.4% through 180 days.

• Monoclonal Antibodies: Clesrovimab and nirsevimab are the two FDA-approved monoclonal antibodies for prevention of RSV in infants and children.  

• • Clesrovimab is a fully human IgG1κ monoclonal antibody targeting antigenic site IV of the RSV fusion (F) protein, which is highly conserved in both prefusion and postfusion conformations. By blocking viral–host membrane fusion, it prevents epithelial cell infection. Fc-engineering with YTE substitutions enhances FcRn binding, extending serum half-life and enabling single-dose, season-long protection.^7,8 Furthermore, the broader epitope targeting may reduce the risk of viral resistance and escape compared to nirsevimab, which binds specifically to the prefusion site Ø.⁹

In the CLEVER phase 2b/3 trial of healthy infants, a single fixed dose of clesrovimab significantly reduced RSV-associated medically-attended LRTIs and hospitalizations, establishing efficacy and extended durability across an entire RSV season.¹⁰

The SMART phase 3 trial evaluated clesrovimab versus palivizumab in 901 infants at increased risk (premature ≤35 weeks or with chronic lung or heart disease). The incidence of RSV-associated hospitalization through 150 days was 1.3% with clesrovimab vs 1.5% with palivizumab, meeting noninferiority criteria, with similar adverse event rates and no anaphylaxis or hypersensitivity reactions.¹¹

• • Nirsevimab is another extended half-life monoclonal antibody that binds to antigenic site Ø on the prefusion F protein—a critical site for viral fusion. This interaction similarly neutralizes RSV entry into host cells. Both agents provide broad neutralization and durable passive immunity throughout a single RSV season.8 In the MELODY phase 3 RCT,  nirsevimab demonstrated substantial efficacy in preventing RSV–associated LRTI among infants. The incidence of medically-attended RSV LRTI was reduced by 74.5% compared with placebo (95% CI, 49.6-87.1; P < 0.001).¹²

Current Clinical Recommendations¹³

Bivalent RSV prefusion F (RSVpreF) vaccine

Indication and timing

• • Pregnant individuals between 32 weeks 0 days and 36 weeks 6 days of gestation.

• • Vaccination should occur seasonally, typically from September through January in most regions of the continental United States.

• • Vaccinate regardless of prior RSV infection, provided the individual was not vaccinated during a previous pregnancy.

Monoclonal Antibodies: Clesrovimab or Nirsevimab

• Routine prophylaxis (first RSV season):

• • Administer RSV immunoprophylaxis to infants <8 months of age born during or entering their first RSV season if:

• • • The mother did not receive the RSVpreF vaccine during pregnancy,

• • • Maternal vaccination status is unknown, or

• • • Delivery occurred <14 days after maternal vaccination.

• • Provide a single dose of nirsevimab or clesrovimab, ideally prior to hospital discharge or within 1 week of delivery

• Second-season prophylaxis (high-risk populations):

• • Administer one dose of nirsevimab to children 8-19 months of age entering their second RSV season who have any of the following:

• • • Chronic lung disease of prematurity requiring medical therapy (eg, corticosteroids, diuretics, or supplemental oxygen) within the past 6 months,
    • Cystic fibrosis with significant pulmonary disease or weight-for-length <10th percentile, or
    • American Indian or Alaska Native heritage with elevated RSV-associated morbidity.
    • Severe immunocompromise: Timing of vaccination should be considered in relation to underlying disease and immunosuppressive therapy, with attention to periods of immune recovery for certain conditions and ensuring that eligible household contacts are appropriately vaccinated to reduce transmission risk.¹⁴

• Timing of administration:

• • Schedule prophylaxis during the RSV season (October-March) in most of the continental United States.
  • Adjust timing based on local RSV circulation patterns in regions with atypical or prolonged seasonality (eg, Alaska, tropical climates).

•   Dosing 

Clesrovimab

• • • Infants <8 months of age: Single dose of 105 mg given by intramuscular (IM) injection prior to or during their first RSV season; weight-independent—one fixed dose for all eligible infants.​

    • Infants undergoing cardiac surgery with cardiopulmonary bypass: Additional 105 mg IM dose after surgery, if initial dose given prior to surgery.​

    • Not indicated for older infants or for a second RSV season.

Nirsevimab

• • • Infants younger than 8 months:

              <5 kg: 50 mg IM, single dose

              ≥5 kg: 100 mg IM, single dose

• • • Children aged 8-19 months at increased risk of severe RSV: 200 mg IM, usually administered as two 100 mg injections at different sites during the same visit prior to their second RSV season.​

The dual availability of maternal vaccination and long-acting monoclonal antibodies offers potential to eliminate severe RSV disease in early infancy. Discussing RSV prevention with parents involves empathetically and clearly explaining the risk and potential severity of infection during early infancy. Clinicians should outline available immunization options—maternal vaccination during pregnancy or infant monoclonal antibody prophylaxis—while considering timing, logistics, and parental preferences. They should listen to concerns or questions that parents may have and address common misconceptions with evidence-based, emphasizing the benefits of prevention in reducing severe illness and hospitalizations. Shared decision-making supports informed, individualized care plans that reflect family values and promote vaccination uptake.

When Thinking Newborn...Think RSV Prophylaxis.

Debunking Common Misconceptions

• Myth: No preventive treatments for RSV are available.

• • Fact: Effective vaccines and monoclonal antibody options exist and are approved for use

• Myth: Only premature or sick infants need RSV prevention.

• • Fact: All infants under 8 months, including healthy term infants, are at risk and benefit from prevention strategies.

• Myth: RSV infection is a one-time illness.

• • Fact: Reinfections with RSV can occur throughout life; early prevention reduces severe outcomes in infancy.

• Myth: RSV can only occur during the winter months

• • Fact: Although more common in the winter, RSV infection can occur throughout the year.
    

References

1. World Health Organization. Summary of WHO Position Paper on Respiratory Syncytial Virus (RSV) Immunization. Accessed October 24, 2025. https://cdn.who.int/media/docs/default-source/immunization/position_paper_documents/hpv/summary_respiratory_syncytial.pdf?sfvrsn=e19b02c9_3
2. CDC. Preliminary estimates of RSV burden for 2024-2025. respiratory syncytial virus infection (RSV). July 9, 2025. Accessed October 24, 2025. https://www.cdc.gov/rsv/php/surveillance/burden-estimates.html
3. American College of Obstetricians & Gynecologists. Maternal Respiratory Syncytial Virus Vaccination. September 2023. Accessed October 24, 2025. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/maternal-respiratory-syncytial-virus-vaccination
4. Houde L, Law AW, Averin A, et al. Annual clinical and economic burden of medically attended lower respiratory tract illnesses due to respiratory syncytial virus among US infants aged <12 months. J Infect Dis. 2025;231(5):1318-1326. doi:10.1093/infdis/jiae544
5. Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics. 2013;132(2):e341-e348. doi:10.1542/peds.2013-0303
6. Hamid S, Winn A, Parikh R, et al. Seasonality of respiratory syncytial virus — United States, 2017–2023. MMWR Morb Mortal Wkly Rep. 2023;72(14);355-361. doi:10.15585/mmwr.mm7214a1
7. Zar HJ, Simões EAF, Madhi SA, et al. Clesrovimab for prevention of RSV disease in healthy infants. N Engl J Med. 2025;393(13):1292-1303. doi:10.1056/NEJMoa2502984
8. Kelleher K, Subramaniam N, Drysdale SB. The recent landscape of RSV vaccine research. Ther Adv Vaccines Immunother. 2025;13:25151355241310601. doi:10.1177/25151355241310601
9. Schaerlaekens S, Jacobs L, Stobbelaar K, Cos P, Delputte P. All eyes on the prefusion-stabilized F construct, but are we missing the potential of alternative targets for respiratory syncytial virus vaccine design? Vaccines. 2024;12(1):97. doi:10.3390/vaccines12010097
10. Zar HJ, Simoes E, Madhi S, et al. 166. A phase 2b/3 study to evaluate the efficacy and safety of an investigational respiratory syncytial virus (RSV) antibody, clesrovimab, in healthy preterm and full-term infants. Open Forum Infect Dis. 2025;12(Supplement_1):ofae631.003. doi:10.1093/ofid/ofae631.003
11. Zar HJ, Bont LJ, Manzoni P, et al. Clesrovimab in infants and children at increased risk for severe RSV disease. N Engl J Med. 2025;393(13):1343-1345. doi:10.1056/NEJMc2506107
12. Drysdale SB, Cathie K, Flamein F, et al. Nirsevimab for prevention of hospitalizations due to RSV in infants. N Engl J Med. 2023;389(26):2425-2435. doi:10.1056/NEJMoa2309189
13. Committee on Infectious Diseases. Recommendations for the prevention of RSV disease in infants and children: policy statement. Pediatrics. 2025;156(5):e2025073923. doi:10.1542/peds.2025-073923
14. Infectious Diseases Society of America. IDSA 2025 Guidelines on the Use of Vaccines for the Prevention of Seasonal COVID-19, Influenza, and RSV Infections in Immunocompromised Patients. Published October 17, 2025. Updated November 4, 2025. Accessed November 14, 2025. https://www.idsociety.org/Seasonal-RTI-Vaccinations-in-Immunocompromised-Patients/