Risk factors for hospitalization, disease severity and mortality in children and adolescents with COVID-19: Results from a nationwide German registry

  1. J Armann
  2. M Doenhardt
  3. M Hufnagel
  4. N Diffloth
  5. F Reichert
  6. W Haas
  7. J Schilling
  8. S Haller
  9. J Hübner
  10. A Simon
  11. DT Schneider
  12. J Brunner
  13. A Trotter
  14. M Roessler
  15. J Schmitt
  16. R Berner

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Abstract

Objective

To characterize the clinical features of children and adolescents hospitalized with SARS-CoV-2 infections and to explore predictors for disease severity.

Design

Nationwide prospective observational cohort study.

Setting

Data collected from 169 out of 351 children’s hospitals in Germany between March 18, 2020 and April 30, 2021 and comparison with the Statutory Notification System.

Participants

1,501 children and adolescents up to 19 years of age with laboratory confirmed SARS-CoV-2 infections who were admitted to children’s hospitals and subsequently reported to the COVID-19 registry of the German Pediatric Infectious Disease Society (DGPI).

Main outcome measures

Admission to intensive care, in-hospital.

Results

As compared to the information in the statutory notification system, up to 30% of all children and adolescents hospitalized in Germany during the study period were reported to the DGPI registry. Median age was three years (IQR, 0-12), with 36% of reported cases being infants. Although roughly half of patients in the registry were not admitted to the hospital due to their SARS-CoV-2 infection, 72% showed infection-related symptoms during hospitalization. Preexisting comorbidities were present in 28%, most commonly respiratory disorders, followed by neurological, neuromuscular, and cardiovascular diseases. Median length of hospitalization was five days (IQR 3-10). Only 20% of patients received a SARS-CoV-2-related therapy. Infants were less likely to require therapy as compared to older children. Overall, 111 children and adolescents were admitted to intensive care units (ICU). In a fully adjusted model, patient age, trisomy 21, coinfections and primary immunodeficiencies (PID) were significantly associated with intensive care treatment. In a bivariate analysis, pulmonary hypertension, cyanotic heart disease, status post (s/p) cardiac surgery, fatty liver disease, epilepsy and neuromuscular impairment were statistically significant risk factors for ICU admission.

Conclusion

Overall, a small proportion of children and adolescents was hospitalized in Germany during the first year of the pandemic. The majority of patients within our registry was not admitted due to COVID-19 suggesting an overestimation of the disease burden even in hospitalized children. Nevertheless, a large proportion of children and adolescents with confirmed COVID-19 reported in Germany could be captured. This allowed for detailed assessment of overall disease severity and underlying risk factors in our cohort. The main risk factors for COVID-19 disease associated intensive care treatment were older patient age, trisomy 21, PIDs and coinfection at the time of hospitalization.

Trial registration

Registry of hospitalized pediatric patients with SARS-CoV-2 infection (COVID-19), DRKS00021506

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  1. ScreenIT

    SciScore for 10.1101/2021.06.07.21258488: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The 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

    Software and Algorithms
    SentencesResources
    Statistical Analysis: Analyses were performed using IBM SPSS v.25.0, R v.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    3.6.3 and Microsoft Excel v.2010.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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:
    Limitations: The main limitation of our analysis is the potential selection bias of cases reported to the DGPI registry. Therefore, the relative risks for ICU admission refer to hospitalized children with SARS-CoV-2 detection only. Disease severity and relative risks might be different in children hospitalized due to COVID-19. Population-based estimations of disease severity based on statutory notification data and estimations of registry coverage are subject to underreporting and possibly reporting bias. Different age medians of hospitalized children within the statutory notification system and the DGPI registry might indicate an underrepresentation of adolescents in the registry potentially resulting from their treatment in adult care units. In addition, the overall low case numbers of pediatric patients treated in the ICU make reliable analysis challenging, especially when aiming to define single comorbidities. Further, end of patient follow-up with end of hospitalization may impair detection of long-term sequelae. Conclusion: Overall, a small proportion of children and adolescents was hospitalized in Germany during the first year of the pandemic. The majority of patients within our registry was not admitted due to COVID-19 suggesting an overestimation of the disease burden even in hospitalized children. Nevertheless, a large proportion of children and adolescents with confirmed COVID-19 reported in Germany could be captured. This allowed for detailed assessment of overall...

    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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  2. Version published to 10.1101/2021.06.07.21258488v1 on medRxiv