The below article appeared in the Fall 2023 WIAAP Newsletter, authored by Margaret Hennessy, MD, FAAP. Dr. Hennessy is a pediatrician with Ascension Wisconsin in Racine, WI, and provides primary care for infants, children, and teens. She delivers care for minor childhood illness and injuries, annual check-ups, well-baby visits, physicals for school and sports and vaccinations. In addition to serving as the chapter’s Immunization and Infectious Disease Champion, Dr. Hennessy serves on the Immunize Wisconsin Advisory Council, and the Wisconsin Council on Immunization Practices.
RSV (respiratory syncytial virus) is a common cause of serious infections in children. RSV causes severe lower respiratory tract disease such as bronchiolitis or pneumonia. In the US, there are approximately 58,000 to 80,000 hospitalizations in young children each year. In addition, there are 100 to 300 deaths each year in children under 5 years related to RSV infections. There are no vaccines licensed in the U.S. to prevent RSV.
in children. We have been using monoclonal antibodies (known as passive immunization) for infants and young toddlers with high-risk conditions for years. However, the vast majority of RSV hospitalizations are in previously-healthy infants born at term. There are no standard medications available to treat RSV in the US. Preventative measures are the best options for reducing the burden of disease in young children.
Previous option for prevention:
Palivizumab (brand name Synagis) is a monoclonal antibody (passive immunization) and has been recommended for use in infants and young toddlers with certain high-risk health conditions since 1998. There is considerable cost to the use of this medication and it requires insurance prior authorization and monthly dosing during RSV season. In addition, since this is categorized as a medication and is a not vaccine, there have been no CDC recommendations for its use and doses are not universally added to WIR (Wisconsin Immunization Registry).
New option for prevention:
New immunizations are out for infants, young children, and adults over age 60 years. They target the fusion (F) protein which is present on the surface of the RSV virion. The new immunization for young children is nirsevimab (brand name is Beyfortus). It is an RSV-F protein inhibitor monoclonal antibody (passive immunization). It was FDA approved in July 2023. It is given as one dose for the season and expected to last for at least
5 months. There is work on another product for persons who are pregnant as a way to protect infants but that is not expected to be available for this fall.
Dosing/timing/details of nirsevimab:
- This is an immunization for all infants who are less than 8 months and is provided in prefilled syringes. It is given as an intramuscular injection and stored in the refrigerator at 2-8 degrees Celsius.
- The prefilled syringes come in 2 strengths
• 50mg (0.5mL) with purple plunger rod (for infants weighing <5 kg)
• 100 mg (1mL) with light blue plunger rod (weighing ≥5kg) - Ideally nirsevimab would be given at birth for all infants born in October through March. If not given in the hospital then it should be given within 7 days of birth.
- All Infants born April through September would get a dose before RSV season in the clinic.
- Infants and toddlers (8 through 19 months) with high-risk conditions would get another dose at the start of their second season. Dose is 200 mg (2 x 100 mg in 1 ml-prefilled syringes).
- Cost is expected to be $495 per dose for the 50 mg and 100 mg doses and $990 for 200 mg.
- Has been approved by VFC for coverage.
High-Risk Conditions for 2nd season dose (8 to 19 months)
- American Indian and Alaska Native Children
- Chronic lung disease of prematurity who required medical support any time during the 6-month period before the start of their second RSV season
- Severe immunocompromising conditions
- Cystic fibrosis who have manifestations of severe lung disease or weight-for-length <10th percentile, previous hospitalization for pulmonary exacerbation in the
first year of life, or abnormalities on chest imaging that persist when stable - Even if a child with a high-risk condition is not quite 8 months, they should still get this second season dose.
What about palivizumab?
Palivizumab is usually given once a month during RSV season for infants and children with high-risk conditions. Nirsevimab may not be available at the start of this RSV season, therefore, infants who qualify for palivizumab should start the series. If nirsevimab becomes available then a child who has received fewer than 5 doses of palivizumab for the 2023-2024 RSV season may get a dose of nirsevimab. They would not get any more doses of palivizumab. Any child, high-risk conditions or not, who receives nirsevimab should not get palivizumab later in the season. That is to say, once you get a dose of nirsevimab then you are done for the season even if you have a high-risk condition. For more information on guidelines for palivizumab see https:// publications.aap.org/pediatrics/article/134/2/415/33013/Updated-Guidance-for- Palivizumab-Prophylaxis-Among
Is nirsevimab a vaccine?
Nirsevimab is a monoclonal antibody product that is a passive immunization. While not technically a “vaccine” in a traditional sense (active immunization), it is being used in a manner similar to routine childhood vaccines and may be referred to as a vaccine by some entities. Nirsevimab confers long-lasting protection from RSV, with protection expected to last at least 5 months (about the length of a typical RSV season). Nirsevimab is part of the Vaccines for Children program.
Because nirsevimab is a monoclonal antibody product, who can administer it?
Nirsevimab comes in a prefilled syringe. In most states, anyone who can administer injections can administer nirsevimab.
What does “shortly before or during” the RSV season mean? When should I start administering nirsevimab?
In most of the continental US, “shortly before or during the season” means that administration of nirsevimab should begin on October 1 and conclude on March 31. In tropical climates (southern Florida, Hawaii, Guam, Puerto Rico, US Virgin Islands and US-affiliated Pacific Islands) and Alaska, RSV circulation patterns may differ. Because timing of the onset, peak and decline of RSV activity may vary, providers can adjust administration schedules based on local RSV activity in the community. The Centers for Disease Control and Prevention (CDC) monitors RSV activity in the United States in collaboration with state and county health departments and commercial and clinical laboratories. These data are available from the National Respiratory and Enteric Virus Surveillance System. Information about local epidemiology can be determined by contacting your local, state, tribal, or territorial health department or other local health authority. Optimal timing for nirsevimab administration is shortly before the RSV season begins, however, it may be given to eligible infants and toddlers who have not yet received a dose at any time during the season.
How long does the RSV protection conferred by nirsevimab last?
Protection is expected to last at least 5 months, about the length of an RSV season.
Are there any contraindications to receiving nirsevimab? Can an infant or young child receive nirsevimab when they are sick?
Nirsevimab is contraindicated in infants and young children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab or to any of its components. Illness or febrile diseases are not contraindications to receiving nirsevimab. The AAP suggests following CDC General Best Practice Guidelines for Immunizations, which recommends that vaccination should be deferred for persons with a moderate or severe acute illness, as this precaution avoids causing diagnostic confusion between the underlying illness and potential adverse effects of immunization. Similar to routine childhood vaccines, mild illness – with or without fever – should not be used as a reason to delay administration of nirsevimab.
If an infant’s mother has received maternal RSV vaccine, should the infant receive nirsevimab?
Maternal RSV vaccine has not yet been approved by the FDA. Once FDA approval occurs, the CDC will issue additional guidance related to this topic.
I have a healthy patient who was 7 months old in October. They present to the clinic in November, at 8 months of age. Can they receive nirsevimab at this visit?
No. CDC recommends that only those healthy infants younger than 8 months of age at the time of administration receive nirsevimab.
Should I recall patients that will be less than 8 months of age at the start of the RSV season?
Yes. Healthy infants become ineligible for nirsevimab at 8 months of age. To realize the full benefits of nirsevimab during the 2023-2024 season, it is recommended that age eligible infants be recalled at the start of the RSV season, before they become ineligible based on age, if nirsevimab is available. Reminder and recall tools are available through the AAP. Nirsevimab may be administered in conjunction with a health maintenance visit or as part of a separate visit.
Should I administer nirsevimab to an infant who is born at the very end of the RSV season?
Yes. Optimal timing for administration is within 1 week after birth during the RSV season. Administering nirsevimab through the end of the season is important because the risk of severe disease is highest during the first few months of life.
Will infants born during the RSV season receive nirsevimab before they are discharged from the hospital?
It is recommended that infants born shortly before and during the RSV season receive nirsevimab within the first week of life, including in hospital settings. Infants with prolonged birth hospitalizations because of prematurity or other causes should receive nirsevimab shortly before or promptly after discharge. During the 23-24 RSV season, if a hospital has been unable to implement administration of nirsevimab, the infant should receive nirsevimab in an ambulatory setting as soon as available. Currently, few hospitals participate in the VFC program, and additional advocacy to support hospital participation is ongoing. Timely and well-coordinated communication between birth hospital and the medical home is important. Equitable access to nirsevimab will require those in a community to work together.
Which children should receive a dose of nirsevimab in their second RSV season?:
- Children with chronic lung disease of prematurity who required medical support (chronic corticosteroid therapy, diuretic therapy or supplemental oxygen) any time during the 6-month period before the start of the second RSV season.
- Children who are severely immunocompromised.
- Children with cystic fibrosis who have manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that persist when stable) or have weight-for- length that is <10th percentile.
- American Indian and Alaska Native children (note that this is a new group for whom second-season prophylaxis is recommended in contrast to the current palivizumab recommendations).
What should I do if nirsevimab is not available for my patient who is at high risk for severe RSV illness?
If nirsevimab is unavailable and the child is eligible to receive palivizumab, then palivizumab should be administered. If < 5 doses of palivizumab are administered and nirsevimab becomes available, the child should receive 1 dose of nirsevimab. No further palivizumab should be administered following receipt of nirsevimab.
Is there a minimum interval between palivizumab and nirsevimab, if an infant has received at least 1 dose (but less than 5 doses) of palivizumab?
The recommended interval between the last dose of palivizumab and a dose of nirsevimab is 1 month (similar to the interval if the infant were to receive another dose of palivizumab).
Can nirsevimab be co-administered with other routine vaccines?
Yes. In accordance with CDC general best practices for immunizations, simultaneous administration of nirsevimab with age-appropriate vaccines is recommended. Nirsevimab is not expected to interfere with the immune response to other vaccines and had similar safety and reactogenicity profiles to vaccines administered without nirsevimab.
If a patient has an adverse reaction to nirsevimab, where should it be reported?
- Adverse events when giving nirsevimab alone should be reported to the FDA’s MedWatch Adverse Event Reporting Program.
- If an adverse event occurs while co-administering nirsevimab with a vaccine, it should be reported to the Vaccine Adverse Event Reporting System.
How do I code and bill for nirsevimab? Will I be paid appropriately?
Report the administration of nirsevimab with code 96372 (injection, subcutaneous or intramuscular), which is lower than typical immunization administration codes. The AAP is advocating for more appropriate payment that accounts for the counseling and scope of work involved in administering nirsevimab. See additional information and Coding Vignettes.
Is nirsevimab financially feasible for my practice? What flexibilities are available when I implement nirsevimab in my practice?
- Payment terms for this season for those ordering direct from Sanofi are 150 days from time of shipment.
- There is no minimum order size. Nirsevimab is packaged as five single dose prefilled syringes per carton in both formulations.
- Nirsevimab is fully returnable upon expiration. Sanofi offers credit (credit based on exact amount returned and the invoice purchase price that is net of prompt pay or other discount(s)) upon expiration on all full and open box Sanofi product(s) directly purchased from Sanofi that are returned within 1 year after the expiration date.
Do I need to report nirsevimab administration to my state immunization information system (IIS)?
Yes. You should report nirsevimab administration to the state IIS in accordance with state policies for reporting of vaccine administration.
Should American Indian and Alaska Native infants and young children from birth–19 months of age receive palivizumab if nirsevimab is unavailable?
If nirsevimab is unavailable, only those high-risk American Indian and Alaska Native infants and young children who meet current criteria for palivizumab should receive it. American Indian or Alaska Native heritage is not an indication for first or second season palivizumab.