Early pandemic molecular diversity of SARS-CoV-2 in children

  1. Ahmed M. Moustafa
  2. William Otto
  3. Xiaowu Gai
  4. Utsav Pandey
  5. Alex Ryutov
  6. Moiz Bootwalla
  7. Dennis T Maglinte
  8. Lishuang Shen
  9. David Ruble
  10. Dejerianne Ostrow
  11. Jeffrey S. Gerber
  12. Jennifer Dien Bard
  13. Rebecca M. Harris
  14. Paul J. Planet

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Abstract

Background

In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children’s Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus.

Methods

We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences. We used genotyping tools to track variants over time and to test for possible genotype associated clinical presentations and outcomes in children.

Results

Our analysis uncovered 13 major lineages that changed in relative abundance as cases peaked in mid-April in Philadelphia. We detected at least 6 introductions of distinct viral variants into the population. As a group, children had more diverse virus genotypes than the adults tested. No strong differences in clinical variables were associated with genotypes.

Conclusions

Whole genome analysis revealed unexpected diversity, and distinct circulating viral variants within the initial peak of cases in Philadelphia. Most introductions appeared to be local from nearby states. Although limited by sample size, we found no evidence that different genotypes had different clinical impacts in children in this study.

Summary

Using sequencing and a novel technique for quantifying SARS-CoV-2 diversity, we investigated 169 SARS-CoV-2 genomes (83 <21 years old). This analysis revealed unexpected diversity especially in children. No clear differences in clinical presentation were associated with the different virus lineages.

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    SciScore for 10.1101/2021.02.17.21251960: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Samples were obtained under CHOP IRB protocol 17-014648 as part of routine clinical care, solely for non-research purposes, carrying minimal risk, and were therefore granted a waiver of informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Briefly, WGS of extracted viral RNA was performed as previously described using Paragon Genomics
    WGS
    suggested: None
    Temporal plots were extracted using a custom script and plotted in GraphPad Prism v7.0a.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    All statistics were performed with STATA version 15.0,
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    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 10.1101/2021.02.17.21251960 on medRxiv