Respiratory syncytial virus (RSV)

The U.S. Centers for Disease Control and Prevention recently reported an increase in respiratory syncytial virus (RSV) detections and RSV-associated emergency department visits and hospitalizations. RSV is a common respiratory virus that usually causes mild, cold-like symptoms, but it can lead to bronchiolitis and pneumonia.¹ Each year in the United States, RSV leads to (on average) 2.1 million outpatient visits; 58,000 hospital visits; and 200 deaths for children less than five years of age due to RSV. Among adults over the age of 65, there were 177,000 hospitalization visits and 14,000 deaths due to RSV.²

Virtually everyone gets RSV in their lifetimes; for most of us, our first exposure came when we were less than six months old and provided lasting immunity. However, the current population under age four has grown up during the COVID-19 pandemic. Due to the isolation and distancing measures to fight that virus, many children were not exposed to RSV as infants and are just encountering it now. The older a child is at first exposure, the more likely that symptoms will be severe. At this time, there is no vaccine against RSV and no curative treatment. Extremely high-risk infants³ less than two years old can receive a prophylactic medication known as Synagis (palivizumab), which can help to prevent RSV disease.

A crisis of viruses

There are several concurrent trends around RSV that are cause for concern:

1. The virus is not adhering to its usual seasonal pattern. RSV infections typically occur fall through spring. However, since the COVID-19 pandemic began, the seasonal pattern has been disrupted and peaks are harder to predict.⁴
2. RSV and flu have not yet peaked. Other viruses are also at play, including adenovirus, enterovirus, and COVID-19. Flu infections began early this year, and although the flu vaccine appears to be quite effective, those levels have been rising rapidly.⁵ The first peak is likely to come in mid to late December. The flu and these other viruses compound the overall problem with RSV; the situation will likely worsen as the respiratory season progresses.
3. This is a series of regional crises. National RSV data doesn’t tell the full story. When we look at national COVID-19 or RSV rates, they are within normal limits, or consistent with data from previous years. However, certain regions are experiencing much higher RSV numbers than other regions.⁶ This suggests we will see waves throughout the country, causing regional stress on health care systems, similar to the early days of the COVID-19 pandemic.⁷
4. Kids being hospitalized for RSV are older and sicker, and there are fewer pediatric beds than ever. The highest rate of hospital admission historically has been in infants under the age of six months. However, over the past few weeks, we have seen a rise in individuals between the ages of one and four, which is generally not common. Hospitalizations of children in all age groups have almost doubled except for children less than six months of age.⁸ Due to lack of exposure during the pandemic, children did not build immunity as infants and now are presenting with more severe symptoms because their first infection is later in life.
   
   This is especially concerning in light of the lack of hospital capacity. From 2008 to 2018, the number of pediatric inpatient unit beds in this country decreased by 12 percent.⁹ This is exacerbated by an acute care nursing shortage that is projected to number 450,000 by 2025.¹⁰

RSV vaccines in development

Although there are currently no RSV vaccines approved in the United States, there are five preventive intramuscular therapies currently projected for potential approval in 2023. They fall into two major categories:

Adult RSV vaccines

Three manufacturers – GSK, Johnson & Johnson, and Pfizer – are developing vaccines to prevent RSV-mediated lower respiratory tract disease in adults ages 60 and over. GSK reported Phase III results showing overall vaccine efficacy against RSV lower respiratory tract disease at 82.6 percent and efficacy against severe RSV lower respiratory tract disease of 94.1 percent. The GSK vaccine is pending approval from the U.S. Food and Drug Administration (FDA) with a May 3, 2023, review date.

Infant RSV preventive therapies

Two agents, both of which have received Breakthrough Therapy Designation from the FDA, are in Phase III development for the prevention of RSV infection in infants. Pfizer’s product would be administered to pregnant women during the late second to third trimester to help protect infants from RSV after birth. Pfizer recently released top-line data from its Phase III trial, reporting 81.8 percent efficacy against severe medically attended lower respiratory tract illness in infants from birth through the first 90 days of life. Efficacy of 69.4 percent was demonstrated for infants over the six-month follow-up period.

Nirsevimab, under development by AstraZeneca/MedImmune/Sanofi, is a one-time antiviral/monoclonal antibody vaccine that would be administered to infants post-birth. It would be an alternative to Synagis for preventing RSV in high-risk premature or immunocompromised infants; it would be the first agent to offer protection to all infants regardless of risk status across the RSV season with a single dose.

The potential market for RSV vaccines has been estimated at $10 billion; the vaccines may be available as soon as fall 2023.