Risk Factors for Severe Disease Among Children Hospitalized With Respiratory Syncytial Virus

Kirolos N, Mtaweh H, Datta RR, et al. JAMA Netw Open. 2025;8(4):e254666. doi:10.1001/jamanetworkopen.2025.4666

Key Points

Question  What are the current risk factors for severe respiratory syncytial virus (RSV) infection given the changing epidemiologic characteristics after the COVID-19 pandemic?

Findings  In this cohort study that included 709 cases of RSV-associated acute respiratory tract infection, severe disease was more likely among children aged 2 years or older with pulmonary and neurologic, neuromuscular, or developmental conditions; children younger than 2 years with a history of prematurity; or children younger than 6 months.

Meaning  Given the identified risk groups, this study suggests there may be benefit associated with prevention strategies, such as universal prophylaxis with monoclonal antibodies in infancy and for children aged 2 years or older in specific high-risk groups.

Abstract

Importance  A resurgence of respiratory syncytial virus (RSV)–associated acute respiratory tract infection (ARI) was observed in 2022 and 2023 after the COVID-19 pandemic. Changes in the demographic characteristics, disease severity, and outcomes of patients were observed, which could impact the identification of risk groups for interventions aimed at reducing the severity of RSV disease.

Objectives  To identify factors associated with severe clinical outcomes among children hospitalized with RSV-associated ARIs in 2022 and 2023.

Design, Setting, and Participants  This observational cohort study, conducted at 2 large, Canadian, tertiary-level pediatric hospitals, comprised all 709 cases of RSV-associated ARI among children younger than 18 years who were admitted to the hospital or intensive care unit (ICU) from July 1, 2022, to June 30, 2023.

Exposure  Diagnosis of RSV-associated ARI.

Main Outcomes and Measures  The primary outcome of severe disease was defined as requiring noninvasive or invasive ventilation or death. Risk factors for severe disease and ICU admission (secondary outcome) were assessed using multivariable Poisson regression, and results were reported as adjusted risk ratios (ARRs) with 95% CIs, with age-stratified models (<2 years and ≥2 years).

Graphical presentation of association between age and
risk ratio for severe disease outcome among children
hospitalized with RSV-confirmed acute respiratory tract illness
when fit with restricted cubic spline and adjusted for sex,
presence of any comorbidities, transfer from hospital, presence
of any viral coinfection, symptom duration, and hospital site.
Reference age is 2 years.

Results  A total of 709 cases (median age, 13.1 months [IQR, 2.0-36.6 months]; 442 boys [62.3%]) were admitted with RSV-associated ARI; 452 (63.8%) were younger than 2 years, and 257 (36.2%) were aged 2 years or older. Severe disease was documented for 204 cases (28.8%). Patients with severe disease were younger than those with nonsevere disease (median age, 2.6 months [IQR, 1.3-16.0 months] vs 18.6 months [IQR, 4.5-39.1 months]; P < .001). Pulmonary disease and use of home oxygen (ARR, 2.47 [95% CI, 1.30-4.68]) and neurologic, neuromuscular, and developmental conditions (ARR, 1.89 [95% CI, 1.03-3.49]) were associated with severe disease among children aged 2 years or older. Among children younger than 2 years, age younger than 3 months (ARR, 2.34 [95% CI, 1.43-3.84]), age 3 to less than 6 months (ARR, 2.79 [95% CI, 1.65-4.70]), and prematurity (ARR, 1.40 [95% CI, 1.03-1.89]) were associated with severe disease.

Conclusions and Relevance  In this cohort study of children hospitalized with RSV in 2022 and 2023, severe RSV disease was more likely among those aged 2 years or older with pulmonary and neurologic, neuromuscular, or developmental conditions. For children younger than 2 years, age younger than 6 months and prematurity were the main risk factors. These findings support prevention strategies for all younger children, including premature infants, with potential benefit for children aged 2 years or older in specific high-risk groups.

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