By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Prevention of respiratory syncytial virus infection is needed but challenging. New studies show some favorable effectiveness on infant outcomes with both vaccination of healthy pregnant women and passive single-dose immunization of prematurely born babies.

SOURCES: Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426-439.

Griffin MP, Yuan Y, Takas T, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020;383:415-425.

Respiratory syncytial virus (RSV) is a main cause of seasonal respiratory tract infection and hospitalization in infants. Worldwide, RSV prompts more than 3 million hospitalizations each year, and more than 100,000 children die of RSV infection each year. Young infants, especially those born preterm with chronic lung disease or congenital heart disease, are at particular risk of infection and death. For more than five decades, vaccines have been developed and tested, still with just limited effectiveness. RSV-specific immune globulin is used in monthly injections to reduce severe disease in high-risk premature babies during the winter season, but there is no feasible, useful preventive measure for more widespread use.

Two new studies demonstrate novel strategies to reduce RSV-related morbidity and mortality. First, healthy pregnant women due to deliver near the start of the RSV season were given an RSV vaccine. Second, an extended half-life RSV-specific monoclonal antibody was given to preterm babies.

Madhi and colleagues vaccinated healthy women at 28 to 36 weeks of gestation with a single-dose intramuscular, RSV fusion protein nanoparticle vaccine in a randomized trial comparing offspring of vaccine-vaccinated and placebo-vaccinated (2:1 ratio) women. A total of 4,636 women were randomized, most in South Africa and the United States. Injection-site reactions were more common with vaccine than placebo injection, but other side effects were not detected with vaccine use.

During the first 90 days of life, medically significant RSV infection was seen in 1.5% of offspring of vaccinated women and 2.4% of offspring of women who received placebo injections. Infection requiring hospitalization (2.1% vs. 3.7%) and infection requiring oxygen use (0.5% vs. 1.0%) were similarly lower in offspring of women who received the true vaccine. The differences were statistically significant but did not reach the pre-determined criterion to be considered “successful.” Nonetheless, severe RSV illness was less likely in offspring of mothers who were vaccinated.

Griffin and colleagues evaluated nirsevimab, an extended half-life monoclonal antibody, in 1,453 infants born following gestations of 29 through 34 weeks. They, too, used a 2:1 ratio of vaccine recipients to placebo recipients. The vaccine consisted of 50 mg of nirsevimab given intramuscularly at the beginning of an RSV season. There were no notable hypersensitivity-type reactions. Infection requiring medical care was less common with vaccine than with placebo (2.6% vs. 9.5%), as was RSV-related hospitalization (0.8% vs. 4.1%).

COMMENTARY

RSV is an RNA virus with two surface proteins responsible for much of its pathogenesis and infectivity.1 The fusion protein accounts for viral entry into the host cell and is the target of natural neutralizing antibodies.1 This protein was the basis of the vaccine tested in pregnant women by Madhi’s group and of the monoclonal antibody used by Griffin’s group. These preventive efforts are more likely to be useful than the attempted 1960s vaccine that prompted formation of non-neutralizing antibodies and, sadly, enhanced T cell responses with worsened disease.1 Although each of these new trials demonstrated statistically significant favorable effects as compared to placebo, each intervention was only about 70% effective in preventing serious RSV illness. Prevention efforts will continue.

So far, prevention efforts have failed to prevent actual infection to a significant degree. But, vaccination still can be useful, since it reduces the risk of being sick enough with infection to require medical care, hospitalization, or oxygen supplementation. And, prevention of illness, even if not preventing all infection, could be effective in saving many of the 100,000-plus lives of children currently dying each year with RSV bronchiolitis.

At the same time, treatment of RSV infection has evolved. While supportive care (fluids, nutrition, comfort measures, oxygen as needed) is all that has proven efficacy, various disproven treatments have generated widespread (though ineffective) use — such as bronchodilators, hypertonic saline, steroids, antibiotics, and high-technology oxygen delivery systems.2-5 Quality improvement efforts can be effective in reducing unnecessary treatments.6-8

All around the planet, there is eager expectation of a vaccine for SARS-CoV-2. It is hoped that such a vaccine will soon be available, effective, and practical. However, one hopes not to see too many correlates with COVID-19 and RSV bronchiolitis. Yes, each is caused by an RNA virus with important surface proteins that can serve as vaccine targets. Yes, each illness has prompted the widespread use of costly, unproven, and potentially dangerous treatments. It is hoped, though, that it will not take decades to find a SARS-CoV-2 vaccine that actually reduces illness — as has been the case for RSV vaccines.

In the meantime, the widespread isolation, masking, and social distancing implemented to reduce COVID-19 also likely will reduce the incidence of RSV bronchiolitis this coming fall and winter.

REFERENCES

  1. Meissner HC. Disarming the respiratory syncytial virus. N Engl J Med 2020;383:487-488.
  2. Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014;134:e1474-e1502.
  3. House SA, Ralston SL. Diagnosis, prevention, and management of bronchiolitis in children: Review of current controversies. Minerva Pediatr 2017;69:141-155.
  4. Hampton E, Abramson E. Less is more: Evidence-based management of bronchiolitis. Pediatr Ann 2017;46:e252-e256.
  5. Ralston SL. High-flow nasal cannula therapy for pediatric patients with bronchiolitis: Time to put the horse back in the barn. JAMA Pediatr 2020; March 23. doi: 10.1001/jamapediatrics.2020.0040. [Online ahead of print].
  6. Ralston S, Comick A, Nichols E, et al. Effectiveness of quality improvement in hospitalization for bronchiolitis: A systematic review. Pediatrics 2014;134:571-581.
  7. Mussman GM, Lossius M, Wasif F, et al. Multisite emergency department inpatient collaborative to reduce unnecessary bronchiolitis care. Pediatrics 2018;141:e20170830.
  8. Ralston SL, Atwood EC, Garber MD, Holmes AV. What works to reduce unnecessary care for bronchiolitis? A qualitative analysis of a national collaborative. Acad Pediatr 2017;17:198-204.