Risk Factors for Poor Outcome or Death in Young Children With Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection: A Systematic Review and Meta-Analysis

Background Respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (RSV-ALRTI) constitutes a substantial disease burden in young children. We aimed to identify all studies investigating the risk factors for RSV-ALRTI poor outcome or death in young children. Methods We carried out a systematic literature review across 7 databases with data from studies published from January 1995 to December 2019. We defined poor outcome as need for prolonged hospital stay, oxygen supplementation, mechanical ventilation, or intensive care unit admission. The quality of all eligible studies was assessed according to modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. We conducted meta-analyses to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for individual risk factors. Results We identified 27 eligible studies, which investigated 20 risk factors for RSV-ALRTI poor outcome and/or death in children <5 years old, compared with children with RSV-ALRTI who did not have poor outcome or who did not die. Among the risk factors, 6 were significantly associated with RSV-ALRTI poor outcome: any comorbid condition (OR, 2.69; 95% CI, 1.89-3.83), congenital heart disease (3.40; 2.14-5.40), prematurity with gestational age (GA) <37 weeks (1.75 (1.31-2.36), prematurity with GA <= 32 weeks (2.68; 1.43-5.04), age <3 months (4.91; 1.64-14.71), and age <6 months (2.02; 1.73-2.35). The meta-estimate ORs for all risk factors other than age <3 months were based on studies using multivariable analysis. For death, only prematurity with GA <37 weeks had a significant meta-estimated OR-3.81 (95% CI, 1.68-8.63)-based on univariable analysis. Conclusions This study represents a comprehensive report of the association between various risk factors and RSV-ALRTI poor outcome or death in young children. More research should be carried out to elucidate risk factors associated with poor outcome or death using multivariable analysis.