Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection

BACKGROUND: 600,000 deaths worldwide are estimated to be directly or indirectly attributable to respiratory syncytial virus (RSV). OBJECTIVES: To determine: (1) the mortality rate; and (2) risk factors for death in children with severe RSV infection. SETTING: 20-bed, regional, multidisciplinary, tertiary, paediatric intensive care unit (PICU) in a university-affiliated children's hospital. METHODS: Cohort study of all children with severe RSV infection covering eight consecutive RSV seasons (1999-2007), using PICU admission as a marker of severity. RESULTS: Of the 406 RSV-positive patients that were admitted to PICU: 98.5% required mechanical ventilation; 35 children died--median age 5.1 months (interquartile range (IQR) 2.4-13.6), length of PICU stay 16 days (IQR 8-31) and 371 survived--median age 2.5 months (IQR 1.2-9), length of PICU stay 5 days (IQR 4-9). The overall PICU RSV mortality was 8.6% with a standardised mortality ratio of 0.76. During the study period 2009 RSV-positive patients were admitted to the children's hospital, giving a hospital RSV mortality rate of 1.7%. Of the deaths, 18 were directly RSV related (RSV bronchiolitis-related mortality PICU 4.4% and hospital 0.9%) as the patients were still RSV positive when they died and 17 children died from non-pneumonitis causes after becoming RSV negative. All of the RSV deaths had pre-existing medical conditions--chromosomal abnormalities 29%, cardiac lesions 27%, neuromuscular 15%, chronic lung disease 12%, large airway abnormality 9%, and immunodeficiency 9%. Nineteen children (56%) had pre-existing disease in two or more organ systems (relative risk (RR) 4.38). Predisposing risk factors for death were pre-existing disease (RR 2.36), cardiac anomaly (RR 2.98) and nosocomial/hospital-acquired RSV infection (RR 2.89). There is an interaction effect between pre-existing disease, nosocomial/hospital-acquired RSV infection and mortality (p<0.001). CONCLUSIONS: Pre-existing disease/comorbidity, in particular multiple pre-existing diseases and cardiac anomaly, is associated with a significantly higher risk of death from severe RSV infection. Nosocomial/hospital-acquired RSV infection is an additional major risk factor for death in children with severe RSV infection.