50 Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020–May 2021
Authors: Farrar Daniel , Drouin Olivier , Hepburn Charlotte Moore , Baerg Krista , Chan Kevin , Cyr Claude , Donner Elizabeth , Embree Joanne , Farrell Catherine , Forgie Sarah , Giroux Ryan , Kang Kristopher , King Melanie , Laffin-Thibodeau Melanie , Luu Thuy-Mai , Orkin Julia , Ouldali Naïm , Papenburg Jesse , Pound Catherine , Price Victoria E , Proulx-Gauthier Jean-Phillippe , Purewal Rupeena , Sadarangani Manish , Salvadori Marina , Thibeault Roseline , Top Karina , Viel-Thériault Isabelle , Kakkar Fatima , Morris Shaun 
Published: October 2022

Abstract

Background
Children living with chronic comorbid conditions are at increased risk for severe COVID-19 disease, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. Age-specific baseline indicators of COVID-19 severity are also needed to evaluate the effectiveness of SARS-CoV-2 vaccination strategies in the paediatric population.

Objectives
In this study, we aimed to 1) identify factors associated with severe COVID-19 in children, and 2) describe rates of hospitalization, intensive care unit (ICU) admission, and severe COVID-19 within specific pediatric age groups.

Design/Methods
We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from March 2020–May 2021. Cases were reported voluntarily by a network of &gt;2800 paediatricians and paediatric subspecialists. SARS-CoV-2 hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease was defined as intensive care, ventilatory or hemodynamic requirements, select organ system complications, or death. Outcomes were described among children aged &lt;6 months, 6–23 months, 2–4 years, 5–11 years, and 12–17 years. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for child age and sex, coinfections, and timing of hospitalization.

Results
We identified 541 children hospitalized with SARS-CoV-2 infection, including 329 (60.8%) with COVID-19-related disease. Median age at admission was 2.8 years (IQR 0.3-13.5) and 42.9% (n=232) had at least one comorbidity. Among COVID-19-related hospitalizations, severe disease occurred in 29.5% of children (n=97/329), including a higher proportion of children aged 2–4 years (48.7%) and 12–17 years (41.3%) (Table 1). Comorbidities associated with severe disease are described in Figure 1, and included technology dependence (adjusted risk ratio [aRR] 1.96, 95% confidence interval [CI] 1.31-2.95), neurologic conditions (e.g. epilepsy and chromosomal/genetic conditions) (aRR 1.87, 95% CI 1.34-2.61), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1.66, 95% CI 1.13-2.42).

Conclusion
While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. Children aged 2–4 years more commonly experienced severe COVID-19 in this study, which was conducted at a time when no children were eligible for SARS-CoV-2 vaccines. Notably, this high-risk group remains without access to approved vaccines. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children.