A Promising Tool to Prevent the “Tripledemic” Resurgence

A Promising Tool to Prevent the “Tripledemic” Resurgence

We now have a new immunization for all infants to prevent a leading cause of pediatric acute respiratory illness and hospitalization: respiratory syncytial virus (RSV). Each year in the United States, RSV infection is responsible for between 58,000 to 80,000 hospitalizations and 100 to 300 deaths in infants and children under 5 years old. According to the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET), RSV-associated hospitalization rates quadrupled from 54.8 per 100,000 in September 2021 to 239.2 per 100,000 in November 2022. 

Tripledemic of RSV, COVID-19 and Flu

Since its approval in 1998, a 5-dose series of palivizumab (Synagis) has been available for a select population of high-risk infants, including those with a history of prematurity, chronic lung disease of prematurity, hemodynamically significant cardiac disease, significantly immunocompromised status, or cystic fibrosis. Now, there are two new options to protect all infants up to 8 months old from severe RSV: the RSVpreF vaccine (Abrysvo, Pfizer), a single-dose, bivalent RSV vaccine administered to pregnant women from 32 to 36 weeks gestation, and Nirsevimab (Beyfortus), a single-dose RSV antibody for all infants younger than 8 months old, regardless of risk factors. High-risk infants between 8 and 19 months old, who previously met criteria for palivizumab and are currently entering their second RSV season, also qualify for this new prophylactic antibody. 

These two new immunization options, along with updated formulations of the annual influenza and COVID-19 booster immunizations, offer an opportunity to prevent a recurrent tripledemic of the COVID-19, RSV, and influenza viruses in the 2022-23 season. The monovalent mRNA COVID-19 immunization formulation, which covers the latest XBB.1.5 strain, was authorized by the Food and Drug Administration (FDA) on September 11, 2023, followed by clinical recommendation for infants and children at least 6 months old by the CDC’s Advisory Committee on Immunization Practices (ACIP). The ACIP continues to recommend routine annual quadrivalent influenza immunization for everyone aged 6 months and older, including a 2-dose primary series for infants during their first season receiving the influenza immunization. Individuals with egg allergy are eligible to receive the immunization without the need for additional safety measures, per updated ACIP recommendations. 

Despite the availability of updated influenza and COVID-19 immunizations, vaccine uptake has been insufficient, particularly in infants and children under 5 years old. Only 61.8% of 12- to 17-year-old adolescents completed the primary COVID-19 immunization series. The completion rates for younger age groups are lower, with 32.9% of 5 to 11-year-olds, 6% of 2- to 4-year-olds, and 4.7% of under 2-year-olds. The demand for the RSV monoclonal antibody immunization currently exceeds the supply, with manufacturing delays and recommendations to prioritize infants weighing less than 5 kilograms and those at the highest risk of severe disease. 

If influenza, COVID-19, and RSV immunizations are administered to the majority of eligible infants and children, we may prevent the repeat of the tripledemic and hope for less severe disease and hospitalizations this season.


  • RSV-NET: Respiratory Syncytial Virus Hospitalization Surveillance Network, Centers for Disease Control and Prevention. https://www.cdc.gov/rsv/research/rsv-net/dashboard.html . Accessed on 10.19.2023.
  • Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection. Pediatrics 2014; 134 (2): 415–420. https://doi.org/10.1542/peds.2014-1665 .
  • Food and Drug Administration: FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants. Press Release. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administrations; 2023.  https://www.fda.gov/news- events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants .
  • Jones JM, Fleming-Dutra KE, Prill MM, et al. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices – United States, 2023. MMWR Morb Mortal Wkly Rep 2023;72:920-925.http://dx.doi.org/10.15585/mmwr.mm7234a4 .
  • Food and Drug Administration. Beyfortus (nirsevimab-alip) product label. Silver Spring,MD: US Department of Health and Human Services, Food and Drug Administration. 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 
  • Grohskopf LA, Blanton LH, Ferdinands JM, Chung JR, Broder KR, Talbot HK. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season. MMWR Recomm Rep 2023;72(No. RR-2):1–25. http://dx.doi.org/10.15585/mmwr.rr7202a1.
  • Jenco M. CDC offers guidance on prioritizing infants for limited nirsevimab supplies. AAP News. 23 Oct 2023. https://publications.aap.org/aapnews/news/26817/CDC-offers-guidance-on-prioritizing-infants-for?autologincheck=redirected
Dr. Marija Rowane


Dr. Marija Rowane is the associate coach of pediatrics, immunology and public health training programs at Northwestern Medical Review, and a columnist/blogger at the Center for Conquest of Longevity.


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