Risk for severe outcomes of COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany

  1. Anna-Lisa Sorg
  2. Markus Hufnagel
  3. Maren Doenhardt
  4. Natalie Diffloth
  5. Horst Schroten
  6. Rüdiger von Kries
  7. Reinhard Berner
  8. Jakob Armann

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Abstract

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources — a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) — in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5–11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities.

Conclusion : Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5–11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in the overall disease burden among all pediatric age groups.

What is Known: • SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking. • Asymptomatic SARS-CoV-2 infections are common in children.
What is New: • We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources. • The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5–11 years old.

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  1. Version published to 10.1007/s00431-022-04587-5
  2. ScreenIT

    SciScore for 10.1101/2021.11.30.21267048: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics: The DGPI registry was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK-110032020) and was assigned clinical trial number DRKS00021506.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The SARS-CoV-2 KIDS study authors reported a seroprevalence of SARS-CoV-2 IgG antibodies of 10.8% (95% CI 8.7, 12.9) for March 2021, and observed no major change through May 2021 [8].
    SARS-CoV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    REDCap is a secure, web-based software platform designed to support data capture for research studies, providing 1) an intuitive interface for validated data capture; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for data integration and interoperability with external sources.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Our analysis was performed using SAS Version 9.4 (SAS Institute, Cary, NC, USA).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    Strengths and limitations: The strength of our analysis lies in its provision of reliable estimates for evaluating the risk of severe manifestations related to SARS-CoV-2 infections in children. Our analysis has several limitations, mainly due to uncertainties in the raw data in the three different sources, which are mostly estimates. The population at risk: We do not know the exact number of SARS-CoV-2 infections in children in Germany. We have estimated the number based upon recently published results of a nationwide, prospective survey of IgG antibodies in pediatric patients in German pediatric hospitals. Limitations include potential selection bias, ELISA cut-off values, precision and the suitability of IgG detected by ELISA to depict SARS-CoV-2 infections in children. Nevertheless, the data are comparable to the standards of other seroprevalence estimates worldwide. On this basis, our data provide the best available estimates for Germany. The number of cases: Reporting to the DGPI register is voluntary, while reporting laboratory-confirmed SARS-CoV-2 infections to the statutory notification system is compulsory. Thus, the latter may be assumed to be more comprehensive. Because case definitions in the DGPI register and the statutory notification system were identical, this provides a reasonable basis for correcting the underreporting of the DGPI cases based upon the statutory notification system. Limiting the analysis to children up to the age of 14 (rather than 17) is a ...

    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.

    About SciScore

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  3. Version published to 10.1101/2021.11.30.21267048v1 on medRxiv