The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection

Summary

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the leading cause of childhood morbidity. Although also an important cause of childhood mortality worldwide, the impact of key risk factors has not been established. A systematic review of 34 articles reporting case fatality rates in young children hospitalized for severe RSV LRTI, according to the presence of underlying RSV risk factors, was conducted. The weighted mean case fatality rate was 1.2% (range, 0–8.3%; median, 0%; n = 10) among preterm infants; 5.2% (range, 2.0–37.0%; median, 5.9%; n = 7) among children with CHD; and 4.1% (range, 0–10.5%; median, 7.0%; n = 6) among children with BPD. Case fatality estimates among children not at high risk (n = 6) ranged from 0% to 1.5% (weighted mean, 0.2%; median, 0.0%). Fatality during hospitalization for severe RSV LRTI is rare among children not at high risk, but occurs more commonly among children at higher risk of RSV LRTI.

Introduction

Lower respiratory tract infection (LRTI) with respiratory syncytial virus (RSV) is a leading cause of hospitalization for severe bronchiolitis and pneumonia among infants and young children worldwide.¹ Infants born preterm, or those diagnosed in infancy with bronchopulmonary dysplasia (BPD; or chronic lung disease of prematurity) or congenital heart disease (CHD) are at particularly high risk;² they have longer hospital stays 3, 4 and are at higher risk of long-term RSV LRTI sequelae such as childhood asthma.⁵

In addition to increased morbidity, severe LRTIs, including due to RSV, are an important cause of childhood mortality worldwide, ⁶ although estimates of the magnitude of the risk of fatality vary. Among infants with underlying risk factors within the national Pediatric Investigators Collaborative Network on Infections in Canada RSV database, fatality rates in some subgroups were as high as 5.3%,⁴ while in a large population-based study in the United Kingdom, fatality rates were as low as 0.2%. ⁷ More recently, a study used data from a systematic review, supplemented with unpublished data, to project that 33 million episodes of RSV LRTI occur annually among children ≤5 years of age worldwide, 3.4 million of these requiring hospitalization.⁶ The global case fatality rate due to severe RSV LRTI was estimated between 1.9% and 5.9%. ⁶ The impact of underlying risk factors on RSV-specific mortality was not considered within that review, although another recent review estimated global fatality rates among children ≤18 years of age hospitalized for RSV LRTI from <1.0% (among those without underlying risk factors), to as high as 37% (among those with CHD). ⁸ Variability in the estimates between the two systematic reviews may be due to the inclusion of individuals at varying underlying RSV LRTI risk, but also due to differences in the age restrictions of the included studies, as younger age is a strong predictor of mortality due to RSV.⁹ Other sources of variability include the underlying epidemiology and distribution of RSV, and the availability of testing and treatment facilities (including access to intensive care units [ICUs]).

Understanding the risk of fatality due to severe RSV LRTI is critical not only to increase awareness of severe RSV-related effects, but also for researchers estimating the economic impact of future treatments or preventive measures. ⁸ Fatality risk may be particularly important for vulnerable populations at higher risk of severe RSV LRTI and its aftereffects2, 8 and younger patients at risk of more severe outcomes.⁸ The objective of this systematic review was to synthesize estimates of case fatality among young children (≤24 months of age) hospitalized for severe RSV LRTI according to underlying risk.