Pediatric critical COVID-19 and mortality in a multinational cohort

  1. Sebastian Gonzalez-Dambrauskas
  2. Pablo Vasquez-Hoyos
  3. Anna Camporesi
  4. Edwin Mauricio Cantillano
  5. Samantha Dallefeld
  6. Jesus Dominguez-Rojas
  7. Conall Francoeur
  8. Anar Gurbanov
  9. Liliana Mazzillo Vega
  10. Steven Shein
  11. Adriana Yock-Corrales
  12. Todd Karsies

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Abstract

Objectives

To understand the international epidemiology of critical pediatric COVID-19 and compare presentation, treatments, and outcomes of younger (<2 years) and older (>2 years) children.

Design

Prospective, observational study from April 1 to December 31, 2020

Setting

International multicenter study from 55 sites from North America, Latin America, and Europe.

Participants

Patients <19 years old hospitalized with critical COVID-19

Interventions

none

Main outcomes measured

Clinical course, treatments, and outcomes were compared between younger and older children. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) for hospital mortality.

Results

557 subjects (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Younger children had more respiratory findings (56% vs 44%), viral pneumonia (45% vs 29%), and treatment with invasive ventilation (50% vs 37). Gastrointestinal (28% vs 69%) or mucocutaneous (16% vs 44%) findings, vasopressor requirement (44% vs 60%), and MIS-C (15% vs 40%) were less common in younger children. Hospital mortality was 10% overall but 15% in younger children (odds ratio 1.89 [95%CI 1.05-3.39]). When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2.6; 95%CI 1.07-6.31) or pulmonary comorbidities (aOR 4.4; 95%CI 1.68-11.5), admission hypoxemia (aOR 2.33; 95%CI 1.24-4.37), and lower respiratory symptoms (aOR 2.83; 95%CI 1.49-5.39). Gastrointestinal (aOR 0.49; 95%CI 0.26-0.92) or mucocutaneous symptoms (aOR 0.31; 95%CI 0.15-0.64), treatment with intravenous immune globulin (aOR 0.33; 95%CI 0.17-0.65), and MIS-C (aOR 0.26; 95%CI 0.11-0.64) were associated with lower mortality.

Conclusions

We identified age-related differences in presentation and mortality for critical pediatric COVID-19 that should prompt more attention to improving management in younger children, especially in developing countries.

Table of Contents Summary

This is a multinational study describing critical pediatric COVID-19 clinical spectrum and related mortality in high and low-middle income countries during 2020.

What’s known on this subject

Pediatric critical illness due to COVID-19 is uncommon and have lower mortality compared to adults when hospitalized. While larger cohorts are from high-income countries (HICs), studies including data from low-middle-income countries (LMICs) remain scarce.

What this study adds

In our multinational cohort of critical pediatric COVID-19, we identified higher mortality than previously reported and age-related disease patterns. Children <2 years old had more respiratory disease and higher mortality, and older children had more non-pulmonary disease and better outcomes.

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  1. ScreenIT

    SciScore for 10.1101/2021.08.20.21262122: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics: This study was approved by the lead site, Nationwide Children’s Institutional Review Board, and each institutional review board at each participating site with a waiver of the need for informed consent (supplemental data, collaborators).
    Consent: Ethics: This study was approved by the lead site, Nationwide Children’s Institutional Review Board, and each institutional review board at each participating site with a waiver of the need for informed consent (supplemental data, collaborators).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study design and setting: CAKE is a prospective, observational cohort study examining the epidemiology and outcomes of children hospitalized for severe or critical COVID-19.
    CAKE
    suggested: (Cake, RRID:SCR_002133)
    We used REDCap (Research Electronic Data Capture, Vanderbilt University) online database hosted by Nationwide Children’s Hospital (Columbus, Ohio, USA).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Statistical analysis was performed using JMP 15 Pro for Mac (SAS Institute, Cary, North Carolina).
    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:
    Our study does have several limitations. As an observational study, we are unable to determine causality between treatments and outcomes. Unrecognized factors might be responsible for the higher mortality observed with certain age groups, clinical presentations, or treatments. Further, while we had a relatively large sample size and high number of deaths compared to other pediatric studies, mortality was still infrequent, limiting our ability to account for confounders. Although we had sites from many countries, our study involved a minority of PICUs in most countries, which may limit generalizability. Even with this limitation, our study involved a wider range of countries than other studies of critical pediatric COVID-19. This allowed us to provide a perspective on populations that have been underrepresented in prior research. We did not account for regional variation in patients, clinical practice, and outcomes but acknowledge that this variability likely impacts outcomes. We are currently gathering data to study this in our cohort. Since our study ended in December 2020, extrapolations of our findings to the current pandemic with viral variants and rising vaccination rates may be challenging. However, the clinical presentations and severity seen in our cohort seem to be similar to what has been anecdotally noted with the rise of the delta variant of SARS-CoV2. Lastly, we do not have data following discharge to capture late mortality or delayed complications such as long C...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.08.20.21262122v1 on medRxiv