Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

  1. Rana Abdelnabi
  2. Robbert Boudewijns
  3. Caroline S. Foo
  4. Laura Seldeslachts
  5. Lorena Sanchez-Felipe
  6. Xin Zhang
  7. Leen Delang
  8. Piet Maes
  9. Suzanne J. F. Kaptein
  10. Birgit Weynand
  11. Greetje Vande Velde
  12. Johan Neyts
  13. Kai Dallmeier

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Abstract

Within one year after its emergence, more than 108 million people contracted SARS-CoV-2 and almost 2.4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1), variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics and new spikes in excess mortality. We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 lineages in Syrian golden hamsters to assess their relative infectivity and pathogenicity in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by ( i ) histological scoring, ( ii ) micro-computed tomography, and ( iii ) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. Overall, we established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.26.433062: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Infection of hamsters Housing and experimental infections of hamsters have been described15–17 and conducted under supervision of the ethical committee of KU Leuven (license P015-2020).
    Randomizationnot detected.
    Blinding15–17 In brief, for histological examination, the lungs were fixed overnight in 4% formaldehyde, embedded in paraffin and tissue sections (5 μm) after staining with H&E scored blindly for lung damage (cumulative score of 1 to 3 each for congestion, intra-alveolar hemorrhage, apoptotic bodies in bronchial epithelium, necrotizing bronchiolitis, perivascular edema, bronchopneumonia, perivascular inflammation, peribronchial inflammation, and vasculitis).
    Power Analysisnot detected.
    Sex as a biological variableIn brief, 6 to weeks old female Syrian hamster (Mesocricetus auratus) were sourced from Janvier Laboratories and kept per two in individually ventilated isolator cages.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    All virus stocks were grown on Vero E6 cells and median tissue culture infectious doses (TCID50) defined by titration using the Spearman-Kärber method as decribed.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    All strains B.1-G, B.1.1.7 and B.1.351 isolated in house were subjected to sequencing on a MinION platform (Oxford Nanopore)28 directly from the nasopharyngeal swabs.
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Statistical analysis All statistical analyses were performed using GraphPad Prism 9 software (GraphPad, San Diego, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.
    • 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 10.1101/2021.02.26.433062 on bioRxiv