Distinct Patterns of Emergence of SARS-CoV-2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio

  1. Huolin Tu
  2. Matthew R Avenarius
  3. Laura Kubatko
  4. Matthew Hunt
  5. Xiaokang Pan
  6. Peng Ru
  7. Jason Garee
  8. Keelie Thomas
  9. Peter Mohler
  10. Preeti Pancholi
  11. Dan Jones

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Following the worldwide emergence of the p.Asp614Gly shift in the Spike (S) gene of SARS-CoV-2, there have been few recurring pathogenic shifts occurring during 2020, as assessed by genomic sequencing. This situation has evolved in the last several months with the emergence of several distinct variants (first identified in the United Kingdom and South Africa) that manifest multiple changes in the S gene, particularly p.Asn501Tyr (N501Y), that likely have clinical impact. We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS-CoV-2 clade 20G variants. One variant, that has become the predominant virus found in nasopharyngeal swabs in the December 2020-January 2021 period, harbors S p.Gln677His (Q677H), affecting a consensus QTQTN domain near the S1/S2 furin cleavage site, nucleocapsid (N) p.Asp377Tyr (D377Y) and membrane glycoprotein (M) p.Ala85Ser (A85S) mutations, with additional S mutations in subsets. The other variant present in two samples, contains S N501Y, which is a marker of the UK-B.1.1.7 (clade 20I/501Y.V1) strain, but lacks all other mutations from that virus. The Ohio variant is from a different clade and shares multiple mutations with the clade 20G viruses circulating in the area prior to December 2020. These two SARS-CoV-2 viruses, which we show are also present and evolving currently in several other parts of North America, add to the diversity of S gene shifts occurring worldwide. These and other shifts in this period of the pandemic support multiple independent acquisition of functionally significant and potentially complementing mutations affecting the S QTQTN site (Q675H or Q677H) and certain receptor binding domain mutations (e.g., E484K and N501Y).

Article activity feed

  1. Version published to 10.1101/2021.01.12.426407v3 on bioRxiv
  2. Version published to 10.1101/2021.01.12.426407v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.01.12.426407: (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 analysis pipeline included BaseSpace, a custom pipeline using GATK tools and DRAGEN RNA Pathogen Detection software (Illumina)
    BaseSpace
    suggested: (BaseSpace, RRID:SCR_011881)
    GATK
    suggested: (GATK, RRID:SCR_001876)
    MAFFT alignment files were analyzed for maximum likelihood using RAxML (Stamatakis, 2006)
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    Prior to formal phylogenetic analyses, both data sets were examined in TempEst version 1.5.3 (Rambaut, 2016) to screen for outliers and assess temporal signal.
    TempEst
    suggested: (TempEst, RRID:SCR_017304)
    Phylodynamic analyses were then carried out in BEAST version 1.10.4 (Suchard, 2018) under a strict clock model with coalescent exponential growth and an HKY substitution model with gamma-distributed rates (4 categories) and unlinked parameters for each codon position.
    BEAST
    suggested: (BEAST, RRID:SCR_010228)
    Tracer version 1.7.1 (Rambaut, 2018) was used to assess convergence.
    Tracer
    suggested: (Tracer, RRID:SCR_019121)
    TreeAnnotater version v1.10.4 (Suchard, 2018) was used to compute the maximum clade credibility (MCC) tree, which was plotted using FigTree version 1.4.4 (Rambaut, 2018).
    FigTree
    suggested: (FigTree, RRID:SCR_008515)

    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: 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.
    • No funding statement was detected.
    • 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.

  4. Version published to 10.1101/2021.01.12.426407v1 on bioRxiv