COVID-19 Hospitalization Among Children <18 Years by Variant Wave in Norway

  1. Robert Whittaker
  2. Margrethe Greve-Isdahl
  3. Håkon Bøås
  4. Pål Suren
  5. Eirik Alnes Buanes
  6. Lamprini Veneti

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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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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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  1. Version published to 10.1542/peds.2022-057564
  2. ScreenIT

    SciScore for 10.1101/2022.03.29.22273093: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: Ethics: Ethical approval for studies on the risk of severe disease by SARS-CoV-2 variant based on data from the national preparedness registry for COVID-19 was granted by Regional Committees for Medical Research Ethics - South East Norway, reference number 249509.
    IRB: Ethics: Ethical approval for studies on the risk of severe disease by SARS-CoV-2 variant based on data from the national preparedness registry for COVID-19 was granted by Regional Committees for Medical Research Ethics - South East Norway, reference number 249509.
    Sex as a biological variableFrom August 2021 there has been a general recommendation that all pregnant women in the second or third trimester get vaccinated.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    An important limitation with severity studies based on reported COVID-19 cases is that undiagnosed cases will affect reported outcome proportions, while systematic differences in undiagnosed cases between groups may affect comparisons. In our study, this is particularly relevant for the comparison of the Alpha wave to other variant waves. The testing strategy was enhanced after the Alpha wave, thus a higher proportion of asymptomatic and mild cases may have been diagnosed among school-age children and adolescents in the Delta and Omicron waves. Also, the small number of outcomes must be considered, which restricted further exploration of our results. Given the low incidence of severe outcomes among child and adolescent COVID-19 cases, which may be further reduced through vaccination (20, 31, 34, 36), analyses of pooled data from several countries or meta-analyses could provide more precise estimates that can better elucidate differences in the risk of these outcomes between VOC in younger age groups. Further, we have based the analysis on variant waves, not cases with known data. However, in models for all COVID-19 cases reported in Norway, results based on these waves were consistent with analyses based on cases with known variant in periods when one variant was superseding another (see supplement A, section 4). Finally, we analysed an Omicron wave when the sublineage BA.1 was the dominant circulating variant. Further studies are still needed to establish differences in dise...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.03.29.22273093v1 on medRxiv