Patient health records and whole viral genomes from an early SARS-CoV-2 outbreak in a Quebec hospital reveal features associated with favorable outcomes

  1. Bastien Paré
  2. Marieke Rozendaal
  3. Sacha Morin
  4. Léa Kaufmann
  5. Shawn M. Simpson
  6. Raphaël Poujol
  7. Fatima Mostefai
  8. Jean-Christophe Grenier
  9. Henry Xing
  10. Miguelle Sanchez
  11. Ariane Yechouron
  12. Ronald Racette
  13. Julie G. Hussin
  14. Guy Wolf
  15. Ivan Pavlov
  16. Martin A. Smith

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Abstract

The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbreak was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess viral diversity (unknown at the time in Quebec) and potential associations with clinical outcomes. We report 264 viral genomes from 242 individuals–both staff and patients–with associated clinical features and outcomes, as well as longitudinal samples and technical replicates. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades with mutations of clinical interest, namely in the Spike protein, that evaded supervised lineage assignment methods–including Pangolin and NextClade supervised lineage assignment tools. We also report that certain symptoms (headache, myalgia and sore throat) are significantly associated with favorable patient outcomes. Our findings demonstrate the strength of unsupervised, data-driven analyses whilst suggesting that caution should be used when employing supervised genomic workflows, particularly during the early stages of a pandemic.

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  1. Version published to 10.1371/journal.pone.0260714
  2. ScreenIT

    SciScore for 10.1101/2021.05.29.21257760: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The presence of SARS-CoV-2 was detected using the Abbott RealTime SARS-CoV-2 assay (Abbott, Chicago, Illinois, United States of America) on a Abbott RealTime M2000rt, a qualitative multiplex real time PCR device that has FDA emergency use authorization for in vitro diagnostic use.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Each sample was barcoded using Native Barcoding Expansion 1-12 and 13-24 kits (EXP-NBD104 and EXP-NBD114, ONT, Oxford, United Kingdom) and sequencing performed on FLO-MIN006 (R9.4.1) flow cells using MinION MK1b, MinION MK1c and GridION sequencers (ONT, United Kingdom).
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Phylogenetics: Assembled SARS-CoV-2 genome sequences with 80% or more completeness and the Wuhan-Hu-1 isolate reference genome (Genbank reference MN908947.3) were submitted to a multiple sequence alignment with MAFFT v7.475 using parameters “--maxiterate 500”.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    The resulting multiple sequence alignment was used to generate a maximum-likelihood phylogeny using MEGA X [7].
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)

    Results from OddPub: Thank you for sharing your code and 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.

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

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  3. Version published to 10.1101/2021.05.29.21257760v1 on medRxiv