Battling RSV: Will Some Be Left Behind?

The RSV Crisis Unveiled

From a pediatrician’s perspective, respiratory syncytial virus (RSV) has been a significant cause of morbidity, if not mortality, in infants and young children. One article states, “The average RSV hospitalization rate was 5.2 per 1000 children < 24 months old. The highest age-specific rate was in infants 1-month-old (25.9 per 1,000 children).” Another study added, “Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1,000 children under 6 months of age and 3 per 1,000 children under 5 years of age. Most of the children had no coexisting illnesses.” So, RSV is not to be taken lightly and is a major concern in the pediatric community.

RSV is a viral infection that causes acute respiratory tract infections in all ages, but seems to have more of a severe effect in younger children and infants with 20-30% developing lower respiratory tract infections like bronchiolitis and/or pneumonia. Almost all children are infected with RSV by the age of 24 months and reinfection throughout life is not uncommon. RSV is contagious and is spread via by direct or close contact with contaminated secretions, which may occur from exposure to large-particle droplets at short distances (typically < 6 feet) or by self-inoculation after touching contaminated surfaces or objects. Viable RSV can persist on environmental surfaces for several hours and for 30 minutes or more on hands. RSV “season” generally begins in the fall and continues through early spring. Pediatricians and emergency rooms usually are on guard for the first signs of RSV “season” because it is the harbinger of the tidal wave of infants and young children with trouble breathing that will flock to pediatric facilities and emergency rooms for medical care.

Supportive Care: The Current Approach

There is no medical treatment for RSV and management of the disease has hinged upon “supportive care”. Supportive care means that there is no definitive treatment once one has become infected. The infection must take its course and the infant or child needs to be supported through all of the consequences of the infection whether it be dehydration of infants from not being able to feed properly to respiratory distress or failure of infants and young children due to the virus attacking the lungs and causing an increase in mucous production. So, the focus has been on preventing the contraction of RSV infection, or at least reducing the severity of the disease, by enhancing the body’s immune system response to the virus through passive immunity (monoclonal and maternal antibodies).

Passive Immunity: Monoclonal and Maternal Antibodies

Palivizumab

The mainstay of prevention for high-risk infants and young children has been a short-acting monoclonal antibody product called Palivizumab (Synagis) since 1998. It has been reserved for infants with a history of chronic lung disease, prematurity (less than or equal to 35 weeks gestational age), and/or hemodynamically significant congenital heart disease which put them at higher risk for severe RSV infection. The infants and young children require monthly intramuscular injections during the RSV season to try and prevent infection (which may require up to 5 doses of the monoclonal antibody). It is purely for disease prevention and is not effective in the treatment of RSV.

RSVpreF

The latest introduction of a vaccine, RSVpreF (Abrysvo), for adults to prevent RSV lower respiratory infection in those 60 years of age and older. It has subsequently been approved to vaccinate pregnant women at 32 through 36 weeks gestational age of their pregnancy to stimulate them to form antibodies that will be passed to their infant and protect them from severe RSV disease up to 6 months after delivery. Maternal RSV vaccination can prevent a significant amount of RSV-specific and all-cause lower respiratory tract infection hospitalizations and lower respiratory tract infections with severe hypoxemia through to 180 days after an infant is born. This is another form of passive immunity for the infant population.

Nirsevimab

Recently, a new monoclonal antibody has been added to the armamentarium for the prevention of RSV infection, Nirsevimab (Beyfortus), and published results showed an approximate 80% relative risk reduction of RSV lower respiratory tract infections and an approximately 62.1% relative risk reduction for hospitalization from RSV-associated lower respiratory tract infection. It is recommended for all infants < 8 months of age entering their first RSV season (usually October 1st – March 31st in the US). Also, only a single intramuscular injection dose is required for the entire RSV season (about 5 months). There is no restriction on who can obtain Nirsevimab for their first RSV season, but only children with chronic lung disease from prematurity, those who are severely immunocompromised, children with cystic fibrosis with severe lung disease or poor weight gain, and American Indian and Alaska Native children should receive a subsequent dose in their second RSV season. The American Academy of Pediatrics recommends that all infants, less than 8 months of age, receive the new monoclonal antibody, Nirsevimab, to prevent severe RSV disease (especially those who are at high risk).

Challenges in Equitable Distribution

Despite having this new, effective product (Nirsevimab) that stands to significantly reduce RSV-related morbidity and mortality for infants entering their first and second seasons of RSV, there is concern that the product will not be distributed equitably because of its cost and the concern for reimbursement of expenses by insurance companies. The cost of Nirsevimab is $495 per dose of 50 mg and 100 mg used for infants entering their first RSV season and $990 per dose for a 200 mg dose used for children entering their second RSV season (because of their larger size). Dr. Sandy L. Chung, the current president of the American Academy of Pediatrics, wrote a letter to Dr. Mandy K. Cohen, the director of the Centers for Disease Control and Prevention, for help implementing the widespread use of Nirsevimab by equitable distribution of the monoclonal antibody and expedited reimbursement of the cost by insurance companies.

So, while Nirsevimab will be available for this upcoming RSV “season”, not all infants will likely be able to receive it due to the cost and availability. It is easy for a pediatric practice to invest in carrying the influenza vaccine where approximately 20 vaccine doses could be obtained for the price of one 50 mg or 100 mg dose of Nirsevimab and, in addition, there are sets of billing codes and procedures for timely reimbursement for influenza vaccination already in place. Furthermore, there are usually arrangements with pharmaceutical companies that allow the return of unused influenza vaccines for a credit or refund to make the financial investment less risky for practitioners.

With Nirsevimab, it is not considered a vaccine and billing codes and procedures for practitioner reimbursement are not formalized. So, it will be risky for medical practices to make the large investment in obtaining the monoclonal antibody (about $10,000 for 20 doses of Nirsevimab for first RSV season infants) if there is going to be a problem or major delay in being reimbursed for the cost of the product. Many medical practices may not be willing to take the risk and wait to obtain the product until the reimbursement logistics are figured out. Furthermore, if there are going to be issues with insurance reimbursement and the cost is just passed on to the families, there will be a significant out-of-pocket cost for those parents willing to pay for Nirsevimab. This process will only emphasize the disparity of medical care through sheer financial inequities because not everyone will be able to individually afford to pay for Nirsevimab out-of-pocket.

Navigating the Road Ahead

RSV is a major concern and in no way taken lightly in the pediatric medical community. It is a disease that has literally plagued young children and infants with significant morbidity and mortality. The excitement that surrounds the possibility of dampening the tidal wave of RSV “season” to a ripple, with new therapeutics, is palpable amongst medical professionals. However, the excitement is tempered by the policies and procedures that need to be put in place to provide adequate distribution to all those who need and desire new scientific products. The case of Nirsevimab highlights the complexities of not only scientific discoveries, but also how to make those scientific discoveries available to the community to provide the promised benefits.

How can healthcare systems work to ensure that new RSV preventive measures, like Nirsevimab, are accessible to all infants who need them?