Burden and Risk Factors for Severe Respiratory Syncytial Virus Infection Among Pediatric Hematopoietic Cell Transplant Recipients

BACKGROUND: Respiratory syncytial virus (RSV) causes substantial morbidity in pediatric hematopoietic cell transplant (HCT) recipients; however, risk factors for severe disease remain incompletely characterized. METHODS: We conducted a multicenter retrospective cohort study across 16 U.S. transplant centers, evaluating children and adolescents (0-19 years) who underwent HCT and developed a laboratory-confirmed RSV infection between 2010 and 2019. Clinical characteristics, laboratory values, and immunosuppressive and transplant history were analyzed. Outcomes included new or increased supplemental oxygen requirement, RSV-related hospitalization, progression to lower respiratory tract infection (LRTI), invasive mechanical ventilation, and 90-day mortality. Univariate logistic regression was used to screen candidate predictors, followed by the least absolute shrinkage and selection operator (LASSO) for variable selection, and multivariable logistic regression to identify independent predictors associated with clinical outcomes. RESULTS: Among 204 pediatric HCT recipients with RSV infection, 41.7% had RSV-related hospitalization, 21.2% required new or increased supplemental oxygen, and 4% required invasive mechanical ventilation within 28 days after the diagnosis. Mortality within 90 days was 5.4%, with one death attributable to RSV. In multivariable models, female sex, younger age (particularly <5 years), neutropenia (ANC <500/mm3), presence of co-pathogen in the respiratory tract and chronic lung disease were independently associated with this oxygen outcome, while non-peripheral graft sources and T-cell-depleting therapy were associated with RSV-related hospitalization. CONCLUSIONS: Severe outcomes are common in pediatric HCT recipients with RSV infection. Younger age, markers of impaired immune recovery, history of chronic lung disease, and T-cell-depleting therapy are major determinants of adverse outcomes. These findings support targeted risk stratification and may inform preventive and treatment strategies in this high-risk population.