Risk factors for severe respiratory syncytial virus infection: a Swedish nationwide cohort study

Abstract Background While risk factors for respiratory syncytial virus (RSV) hospitalization are well known, less is understood about predictors of severe outcomes. We aimed to identify risk factors for severe outcomes of RSV infection in children aged 0-18 years, and the prevalence of comorbidities in different age groups. Methods This is a register-based cohort study including all children born in Sweden between 2001-2022. Data on RSV-related ICD-10 diagnoses, sociodemographic factors, and comorbidities were retrieved from national registers. Outcomes were RSV-related death, Intensive Care Unit (ICU) admission, and prolonged hospitalization (≥7 days). Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were estimated for the full cohort and for the subpopulation of children with a record of RSV infection diagnosis. Results Among 2,354,302 children, 38,919 (1.7%) had an RSV diagnosis. Of these, 4,243 (10.9%) experienced severe outcomes (death: n = 27; ICU: n = 1,210; prolonged hospitalization: n = 3,253). The strongest associations were seen for birth in winter (HR: 2.96, 95%CI 2.53-3.46), small for gestational age (aHR: 3.76, 95%CI: 2.96-4.76), twinship (aHR: 3.41, 95%CI: 2.78-4.19), having siblings 0-3 years old (aHR: 2.92, 95%CI: 2.58-3.31), having a sibling who was hospitalized for lower respiratory tract infection before age 4 (aHR: 2.39, 95% CI:1.53-3.72) and comorbidities (aHRs >4). Similar, but attenuated, associations were seen in the RSV subpopulation. Among children experiencing severe disease outcomes, the proportion of comorbidities was lower in those 0-2 months than in older children (31.8% vs 56.2%, p < 0.001). Conclusions Several factors and comorbidities are linked to severe RSV outcomes. However, most severe cases occur in healthy full-term infants, especially in the first three months, highlighting the need for prevention strategies targeting all vulnerable infants or based on broader risk stratifications, rather than relying solely on comorbidities. Key messages • RSV prevention strategies should target all children, including healthy full-term infants, as severe outcomes can occur even in the absence of comorbidities, especially in the first months of life. • Certain factors (such as young age, birth in winter, small for gestational age, twinship, preschool-aged siblings), along with comorbidities, significantly contribute to severe RSV outcomes.