Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022). Patients <17 years hospitalized for COVID-19 (excluding incidental SARS-CoV-2) at 13 pediatric hospitals were included. Lineages were defined via genetic sequencing or dominant lineage upon hospitalization. Severe disease included intensive care, ventilatory/hemodynamic requirements, systemic complications, and/or death.

Results: We analyzed 3218 COVID-19 hospitalizations, including 81.4% admitted during Omicron predominance. Median age was highest among Delta cases (2.9 years, interquartile range [IQR] 0.2-10.9) and lowest among Omicron BQ.1 cases (0.6 years, IQR 0.2-1.8). Severe COVID-19 remained common in Omicron vs. ancestral cases (27.2% vs. 23.2%). The proportion of hospitalized cases aged 5-16 years declined following the introduction of age-specific COVID-19 vaccines. Vaccination reduced the risk of in-hospital severe disease for ages 12-16 years (two vs. zero doses; adjusted risk ratio 0.49, 95% confidence interval 0.32-0.77).

Conclusion: More children were hospitalized with Omicron lineages than all prior lineages. COVID-19 vaccination was associated with a lower burden of severe disease among ages 5-16 years.

Impact Statement: This study estimates the effect of SARS-CoV-2 lineage, Omicron sub-lineage, and vaccination on COVID-19 disease severity, using data from two Canadian national surveillance programs. Few national studies describe the clinical presentation and severity of Omicron sub-lineages among hospitalized children. In Canada, Omicron lineages were associated with substantially more pediatric COVID-19 hospitalizations than all prior lineages combined, though risk of severe COVID-19 was highest during the Delta period. COVID-19 vaccines were associated with reductions in hospitalization (ages 5-16 years) and severe disease (ages 12-16 years) across Omicron sub-lineages.