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. 2022 Nov:15:100337.
doi: 10.1016/j.lana.2022.100337. Epub 2022 Aug 1.

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021

Daniel S Farrar  1 , Olivier Drouin  2   3 , Charlotte Moore Hepburn  4   5 , Krista Baerg  6   7 , Kevin Chan  8   9   10 , Claude Cyr  11 , Elizabeth J Donner  12 , Joanne E Embree  13   14 , Catherine Farrell  15 , Sarah Forgie  16   17 , Ryan Giroux  18 , Kristopher T Kang  19 , Melanie King  20 , Melanie Laffin Thibodeau  20 , Julia Orkin  4   21 , Naïm Ouldali  22 , Jesse Papenburg  23   24 , Catherine M Pound  25 , Victoria E Price  26 , Jean-Philippe Proulx-Gauthier  27 , Rupeena Purewal  6   28 , Christina Ricci  29 , Manish Sadarangani  19   30 , Marina I Salvadori  31 , Roseline Thibeault  32 , Karina A Top  33 , Isabelle Viel-Thériault  32 , Fatima Kakkar  22 , Shaun K Morris  1   8   34   35
Affiliations

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021

Daniel S Farrar et al. Lancet Reg Health Am. 2022 Nov.

Abstract

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada.

Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization.

Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39).

Interpretation: 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. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children.

Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Keywords: COVID-19; Children; Hospitalization; Risk factors; SARS-CoV-2; Surveillance.

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Conflict of interest statement

Kevin Chan is Chair of the Acute Care Committee of the Canadian Paediatric Society, and served on the billing/finance committee of the Pediatric Section of the Ontario Medical Association. Catherine Farrell is Chair of the Scientific Steering Committee for the Canadian Paediatric Surveillance Program and a member of the Board of Directors of the Canadian Critical Care Society. She has received funding from Health Canada and the Canadian Institutes of Health Research, as well as an honorarium for a presentation at a continuing education conference from the Université de Sherbrooke. Sarah Forgie is the President of the Association of Medical Microbiology and Infectious Disease Canada, and received an honorarium for participation in the Senior Medical Advisory Committee at Ryerson Medical School. Fatima Kakkar has received salary support for a protected time from the FRQS Chercheur Boursieurs Program, and received honoraria for presentations given to the Association des Pédiatres du Québec. She has also served on the Quebec COVID-19 maternal-child health advisory committee and received grants from FRQS Reseau SIDA Maladies Infectieuses and Foundation of Stars. Charlotte Moore Hepburn is the Director of Children's Mental Health of Ontario, and the Director of medical affairs for the Canadian Paediatric Society and the Canadian Paediatric Surveillance Program. Shaun Morris has received honoraria for lectures from GlaxoSmithKline. He was a member of ad hoc advisory boards for Pfizer Canada and Sanofi Pasteur. Jesse Papenburg has received consultant fees from Merck, honoraria from Astra-Zeneca and Seegene, and is a voting member of the National Advisory Committee on Immunization. He is also site principal investigator for industry trials by MedImmune, Merck, Astra-Zeneca, and Sanofi, and is Medical Lead of the Study Steering Committee for AbbVie. Rupeena Purewal is a consultant for Verity Pharmaceuticals. Christina Ricci and Marina Salvadori are employees of the Public Health Agency of Canada. Manish Sadarangani has been an investigator on projects, unrelated to the current work, funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. He is also Chair/Deputy Chair of Data Safety Monitoring Boards for two COVID-19 vaccine trials. Karina Top received a grant from GlaxoSmithKline to her institution outside the submitted work. No other competing interests were declared.

Figures

Figure 1
Figure 1
Risk ratios for severe COVID-19 by continuous child age. Risk factors analysis was conducted among children hospitalized for COVID-19-related disease only (n=330). Age was analyzed using Poisson regression with robust standard errors, where age was entered into the model as a restricted cubic spline with four knots. Predicted probabilities of severe disease were then exponentiated to visualize continuous risk ratios. The analysis adjusted for sex, comorbid conditions (categorized as none, non-complex, or complex), concomitant infections (any vs. none), and timing of hospitalization (first, second, or third wave).
Figure 2
Figure 2
Risk ratios for severe COVID-19 by sex, concomitant infections, timing of hospitalization, and chronic conditions. Risk factors analysis was conducted among children hospitalized for COVID-19-related disease only (n=330). Adjusted risk ratios (aRR) were calculated using Poisson regression with robust standard errors. The x-axis depicts risk ratios by multiples of two (i.e. 2–4–6–8 and 1/2–1/4–1/6–1/8–1/10). The primary model included continuous age (as analyzed in Figure 1), sex, concomitant infections, timing of hospitalization, and chronic condition category (i.e. none/unknown, non-complex, complex). Separate models were then run for each specific chronic condition, by substituting the overall chronic condition category with only the condition of interest. Finally, age <1 month and prematurity status were assessed in a separate model containing only children < 1 year old (n=140, including 20 severe cases), and did not adjust for additional variables due to the smaller available sample size. 1All cases of physician-reported obesity, regardless of the presence of height and weight data to calculate zBMI.
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