Study identifies risk factors for severe COVID-19 in hospitalized children in Canada

In a recent study posted to the medRxiv* preprint server, researchers evaluated the risk factors for severe coronavirus disease 2019 (COVID-19) among hospitalized children in Canada.

Background

COVID-19 is reported to be mild among children. However, severe outcomes such as hospitalizations and deaths have also been reported in children. Chronic comorbidities have been important prognostic factors to assess disease progression.

However, evidence on the risks associated with comorbidities has been limited, albeit diabetes, neurological and pulmonary disorders, and multiple comorbidities have been reported to be associated with severe COVID-19.

Further, the age-based risk estimates of severe COVID-19 have been mixed with jurisdictional differences and may be confounded by multisystem inflammatory syndrome in children (MIS-C). Thus, robust indicators of specific risk factors in children are required to guide evidence-based decisions by policymakers and clinicians.

About the study

In the present prospective study, researchers identified factors associated with severe COVID-19 among hospitalized children in Canada, before the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and the authorization of COVID-19 vaccinations for children.

Data were obtained on children below 18 years with laboratory-confirmed-COVID-19 via the Canadian Paediatric Surveillance Program (CPSP) which was conducted between April 2020 and May 2021. The data included their age, body mass index z-score (BMIZ), SARS-CoV-2 exposure and test reports, chronic comorbidities, clinical manifestations, reasons for hospitalization, and outcomes including the level of care required and treatments/supports administered. The weekly incident cases were reported by online case reporting by more than 2,800 pediatricians via the Canadian Network for Public Health Intelligence.

Hospitalizations were classified as those associated with COVID-19, incidental infections, or social purposes/infection control admissions. Severe COVID-19 was described as COVID-19 cases that required intensive care unit (ICU) admissions, hemodynamic support or mechanical ventilation, and had pulmonary, cardiac, or neurological complications, or deaths. Children diagnosed with MIS-C by polymerase chain reaction (PCR) during their hospital stay were excluded from the study.

The hospitalized children were stratified by age into below six months, six to 23 months, two to four years, five to 11 years, and 12 to 17 years.  The timing of hospitalization was categorized as the first wave between March and August 2020, the second wave between September 2020 and February 2021, and the third wave between March and May 2021.

Clinical and demographical data were assessed using percentages, frequencies, interquartile ranges (IQR), and medians. Risk factors for severe COVID-19 were evaluated using multivariable Poisson regression analysis, after data adjustments for sex, age, the timing of hospital admission, and concomitant infections and were reported as adjusted risk ratios (aRR).

Results

A total of 544 hospitalized children were identified, of which 60% were COVID-19-associated and 40% were associated with incidental infections or for social purposes or infection control. Over 15%, 50%, and 35% of hospitalizations occurred during the first, second, and third COVID-19 waves with peaks in April 2020, January 2021, and April 2021, respectively. Hospitalizations were reported across all Canadian regions, most frequently from Ontario (42%) and Quebec (36%). Concomitant infections were reported in 8% of cases, most commonly urinary tract infections.

Among the hospitalized COVID-19 patients (n=330), 70% of them had non-severe COVID-19, whereas 30% had severe COVID-19. The mean age was 1.9 years (IQR 0.1 to 13.3), significantly higher among severe COVID-19 patients (6.5 years, IQR 1.5 to 14.8) than non-severe COVID-19 (0.8 years, IQR 0.1 to 9.7) patients.

Over 40% (n=142) of the patients had chronic comorbidities such as pulmonary disorders like bronchopulmonary dysplasia and uncontrolled asthma (aRR 1·6), neurological disorders such as epilepsy, and specific chromosomal disorders, (aRR 1·8), and technology dependence with parenteral nutrition, home oxygen or tracheostomy requirements (aRR 2); BMIZ >3 (aRR 1.9); premature births (3.5-fold higher risk of severe COVID-19).

About 18% of children had ICU admissions for a mean four-day period (IQR 2 to 7) with requirements of mechanical ventilation (7.6%) and vasopressors (2.4%). Overall, 33.3% (n=108) of the children needed hemodynamic or pulmonary support. Notably, immunosuppression (aRR 0.4) and cancers (aRR 0.7) were not associated with COVID-19 severity.

Five deaths were reported among COVID-19 children with acute complications, at an average age of eight years. Of note, children aged two to four years had the highest number of severe COVID-19 cases (49%), followed by age groups of 12 to 17 years (41%), five to 11 years (37%), six to 23 months (28%), and below six months of age (14%). Likewise, children aged two to four years had higher ICU admissions (33%), and children aged 12 to 17 years more frequently required hemodynamic or pulmonary support (51%), indicating that age and COVID-19 severity were significantly but non-linearly associated.

To summarize, the study findings showed that while severe COVID-19 was observed across all ages, the children aged two to four years and 16 to <18 years were at a higher risk. In addition, neurologic and pulmonary disorders and technology dependence were highly associated with COVID-19 severity.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.