SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

  1. Bobo Wing-Yee Mok
  2. Conor J. Cremin
  3. Siu-Ying Lau
  4. Shaofeng Deng
  5. Pin Chen
  6. Anna Jinxia Zhang
  7. Andrew Chak-Yiu Lee
  8. Honglian Liu
  9. Siwen Liu
  10. Timothy Ting-Leung Ng
  11. Hiu-Yin Lao
  12. Eddie Lam-Kwong Lee
  13. Kenneth Siu-Sing Leung
  14. Pui Wang
  15. Kelvin Kai-Wang To
  16. Jasper Fuk-Woo Chan
  17. Kwok-Hung Chan
  18. Kwok-Yung Yuen
  19. Gilman Kit-Hang Siu
  20. Honglin Chen

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Abstract

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.28.271635: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    For animal challenge, viral stocks were prepared after two serial passages of isolated virus in Vero E6 cells in Dulbecco’s Modified Eagle Medium (DMEM) (Thermo Fisher Scientific) supplemented with 5% fetal bovine serum (Thermo Fisher Scientific), and 100 IU penicillin G/ml and 100 ml streptomycin sulfate/ml (Thermo Fisher Scientific).
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Images were obtained with an Olympus BX53 semi-motorized fluorescence microscope using cellSens imaging software.
    cellSens
    suggested: None
    Read counts were extracted using the “--quantMode GeneCounts” argument with STAR for each sample.
    STAR
    suggested: (STAR, RRID:SCR_015899)
    Volcano plots were generated using the EnhancedVolcano R package (www.bioconductor.org/packages/release/bioc/vignettes/EnhancedVolcano/inst/doc/EnhancedVolcano.html).
    EnhancedVolcano
    suggested: (EnhancedVolcano, RRID:SCR_018931)
    Boxplots were generated with ggplot2 R package (Wickham, 2016).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Principal component analysis: Log2FoldChange values for hamster DEGs for infections with each of the five isolates, contrasted to samples from uninfected animals, were extracted from the results of DESeq2.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    Evolutionary analysis was performed in accordance to the protocol set by the author (Hall, 2013), using MEGA X software.
    MEGA X
    suggested: None
    Sequences were aligned using MUSCLE, with positions with less than 95% coverage being excluded (Edgar, 2004).
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    Gene set enrichment analysis (GSEA): Comprehensive lists of known mouse-hamster gene orthologues were compiled from the BioMart database (Smedley et al., 2015)
    Gene set enrichment analysis
    suggested: (Gene Set Enrichment Analysis, RRID:SCR_003199)
    BioMart
    suggested: (biomaRt, RRID:SCR_019214)
    Heatmaps of significant GO groups were generated using the ComplexHeatmap R package (Gu et al., 2016).
    ComplexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)
    A phylogenetic tree was constructed with PhyML (v3.0) using the maximum likelihood algorithm.
    PhyML
    suggested: (PhyML, RRID:SCR_014629)

    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

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  2. Version published to 10.1101/2020.08.28.271635v1 on bioRxiv