Abstract

There is limited evidence on whether the relative severity of coronavirus disease 2019 (COVID-19) in children and adolescents differs for different severe acute respiratory syndrome coronavirus 2 variants. We compare the risk of hospitalization to acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C) among unvaccinated persons <18 years with COVID-19 (cases) between waves of the Alpha, Delta, and Omicron (sublineage BA.1) variants in Norway. We used linked individual-level data from national registries to calculate adjusted risk ratios (aRR) with 95% confidence interval (CI) using multivariable log-binomial regression. We adjusted for variant wave, demographic characteristics, and underlying comorbidities. We included 10 538 Alpha (21 hospitalized with acute COVID-19, 7 MIS-C), 42 362 Delta (28 acute COVID-19, 14 MIS-C), and 82 907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalization with acute COVID-19 was lower in the Delta (aRR: 0.53, 95% CI: 0.30-0.93) and Omicron wave (aRR: 0.40, 95% CI: 0.24-0.68), compared to the Alpha wave. We found no difference in this risk for Omicron compared to Delta. The risk of MIS-C was lower for Omicron, compared to Alpha (aRR: 0.09, 95% CI: 0.03-0.27) and Delta (aRR: 0.26, 95% CI: 0.10-0.63). We do not find clear evidence that different variants have influenced the risk of hospitalization with acute COVID-19 among unvaccinated children and adolescents in Norway. The lower risk of this outcome with Omicron and Delta may reflect changes in other factors over time, such as the testing strategy, maternal vaccination and/or hospitalization criteria. The emergence of Omicron has reduced the risk of MIS-C.

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