Respiratory syncytial virus (RSV) is a major cause of childhood morbidity across the world and mortality in low- to middle-income countries.1 In the United States, RSV represents the most frequent cause of hospitalization in the first year of life.2 As efforts are gaining momentum to develop new strategies (vaccines and monoclonal antibodies) to prevent RSV infections,3 it becomes even more important to have precise data on the disease burden. In this issue of Pediatrics, Rha et al4 report an active, prospective, multicenter, population-based surveillance study of the burden of RSV hospitalizations among US children <5 years of age from November 2015 to June 2016. The study has significant strengths because it includes 7 US pediatric hospitals of diverse geography; the authors use a broad definition of acute respiratory infections and proven RSV infection based on validated, polymerase chain reaction–based diagnostic assays. Among 4716 eligible children, the investigators enrolled 3001 (64%) and obtained adequate samples in 2983 (99%). Of those, 2969 children had conclusive results, and 1043 (35%) were positive for RSV. The rate of RSV-associated hospitalizations was 2.9% per 1000 in children <5 years old and 6.3% per 1000 in those <24 months old.
With these data, researchers confirm the huge impact that RSV infections have on children’s health and on the health care system. The study investigators provide many details about hospitalization rates and disease severity across age groups, gestational ages, races, and ethnicities, all of which deserve careful review. Among all children positive for RSV, 339 (33%) had chronic comorbidities or were <2 years old with history of prematurity, indicating that the majority of children hospitalized with RSV infection are previously healthy with no known risk factors. In contrast, children positive for RSV were less likely to have a chronic comorbidity or history of prematurity (33%) than RSV-negative children (46%), confirming previous observations suggesting that RSV has greater capability to cause severe disease in previously healthy children than other respiratory viruses.5
By age groups, the highest rates of hospitalizations were documented in 1-month-old infants (25.1 per 1000 children), and the overall rate of hospitalization in children <6 months was 14.4 per 1000 children. Furthermore, children <6 months old represented 50% of all hospitalizations. With these data, the researchers provide support for the preventive strategies focused in this age group, such as maternal vaccination and monoclonal antibodies, that are in a more advanced phase of development.6,7 In contrast, the data clearly reveal the urgent need to develop vaccines to protect older infants and children.1,8–10 For premature children <24 months of age, the overall rate of hospitalization was 9.6 per 1000 children compared with 5.6 per 1000 in term children. Further analyses by gestational age revealed hospitalization rates of 15.4 (95% confidence interval [CI]: 7.3–24.3) per 1000 for those <29 weeks’ gestational age (WGA), 13.8 (95% CI: 8.1–20.8) per 1000 in the 29 to 31 WGA group, and 11.3 (95% CI: 8.1–14.6) per 1000 for those 32 to 34 WGA. With these data, the investigators confirm the significantly increased RSV-associated morbidity among premature infants and suggest that there might be limitations to quantify precisely the risk according to gestational age.
The authors also evaluated differences in the burden of RSV hospitalizations according to patient demographic characteristics. In children <5 year old, rates of hospitalization were higher in boys than in girls (3.3 vs 2.6 per 1000) and in Hispanic or Latinx (3.5 per 100) and non-Hispanic African American children (3.4 per 1000) compared with non-Hispanic white children (2.5 per children). The authors offer no explanation or potential mechanisms for these differences, suggesting that this is an important topic for future research. In terms of clinical outcomes, the median (interquartile range) duration of hospitalization was 2 (1–3) days. As in earlier studies, children with comorbidities and history of prematurity were more likely to be admitted to the ICU. There were no deaths reported in the study.
Despite its major strengths, the study has limitations. The respiratory season had already started in some clinical sites, highlighting the need to extend the surveillance beyond the traditional RSV season to capture all RSV hospitalizations. Furthermore, by design, the study researchers failed to capture the burden of disease in the outpatient setting, which is significantly larger than among hospitalized children and is also associated with significant acute and long-term morbidity.11–13
With this study, the researchers confirm the need to develop preventive strategies for RSV infection that target previously healthy children as well as those at high risk and the importance of those preventive strategies extending beyond the first 6 months of life. They also highlight the need for further prospective studies, conducted in both high- and limited-resource countries, that will require extension outside the typical RSV season to precisely capture the complete RSV burden of disease among both hospitalized children and outpatients, as well as their long-term morbidity. Only by accurately assessing the true burden of RSV-associated morbidity will we be able to precisely measure the impact of RSV preventive interventions that we are able to incorporate into clinical practice.
FUNDING: No external funding.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-3611.
POTENTIAL CONFLICT OF INTEREST: Dr Mejias has received research grants from National Institutes of Health and Janssen and fees for participation in advisory boards from Janssen and Roche. Dr Ramilo has received research grants from the NIH, Bill and Melinda Gates Foundation, and Janssen; fees for participation in advisory National Institutes of Health from Merck, MedImmune and Sanofi-Pasteur, and Pfizer; and fees for lectures from Pfizer.
FINANCIAL DISCLOSURE: Dr Mejias has received research grants from the National Institutes of Health and Janssen and fees for participation in advisory boards from Janssen and Roche. Dr Ramilo has received research grants from the National Institutes of Health, Bill and Melinda Gates Foundation, and Janssen; fees for participation in advisory boards from Merck, MedImmune and Sanofi-Pasteur, and Pfizer; and fees for lectures from Pfizer.