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Observational Study
. 2025 Apr 1;8(4):e254666.
doi: 10.1001/jamanetworkopen.2025.4666.

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

Nardin Kirolos  1 , Haifa Mtaweh  1   2   3 , Rohini R Datta  4 , Daniel S Farrar  4 , Claire Seaton  5   6   7 , Jeffrey N Bone  8 , Fiona Muttalib  6   7   9 , Caitlyn L Kaziev  3 , Jonathan Fortini  9 , Sanjay Mahant  1   3   10   11 , Aaron Campigotto  12   13 , Gabrielle Freire  1   14 , Rae S M Yeung  15   16   17   18 , Jonathan H Rayment  6   7   19 , Connie Yang  6   7   19 , Jocelyn A Srigley  7   20   21 , Manish Sadarangani  6   7   22 , Francine Buchanan  23 , Shaun K Morris  1   3   4   24   25 , Peter J Gill  1   3   10   26 ; READAPT-Kids Study Group Members
Collaborators, Affiliations
Observational Study

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

Nardin Kirolos et al. JAMA Netw Open. .

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).

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mtaweh reported receiving the Research Scholar Award from the American Gastroenterology Association outside the submitted work. Dr Seaton reported receiving grants from the Rural Coordination Centre of British Columbia during the conduct of the study. Mr Fortini reported receiving grants from the Public Health Agency of Canada and the SickKids Foundation during the conduct of the study. Prof Yeung reported receiving grants from the Canadian Institutes for Health Research during the conduct of the study. Dr Rayment reported receiving personal fees from Vertex Pharmaceuticals and Boehringer Ingelheim and grants from Vertex Pharmaceuticals outside the submitted work. Dr Sadarangani reported receiving grants from GlaxoSmithKline paid to his institute, Merck paid to his institute, Moderna paid to his institute, Pfizer paid to his institute, and Sanofi Pastur paid to his institute outside the submitted work. Dr Buchanan reported receiving grants from the Canadian Institutes for Health Research during the conduct of the study and personal fees from the American Academy for Cerebral Palsy and Developmental Medicine outside the submitted work. Dr Morris reported receiving grants from the Public Health Agency of Canada during the conduct of the study and personal fees from GlaxoSmithKline, Pfizer, and Sanofi Pasteur outside the submitted work. Dr Gill reported receiving grants from the Canadian Institutes of Health Research, the PSI Foundation, and the Hospital for Sick Children outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Age and Risk Ratio for Severe Disease Outcome Among Children Hospitalized With Respiratory Syncytial Virus (RSV)–Confirmed Acute Respiratory Tract Illness
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.
Figure 2.
Figure 2.. Forest Plot of Risk Factors for Severe Disease Among Children Hospitalized With Respiratory Syncytial Virus (RSV)–Confirmed Acute Respiratory Tract Illness Stratified by Age Groups
ARR indicates adjusted risk ratio.
See this image and copyright information in PMC

References

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