Host barriers to SARS-CoV-2 demonstrated by ferrets in a high-exposure domestic setting

  1. Kaitlin Sawatzki
  2. Nichola J. Hill
  3. Wendy B. Puryear
  4. Alexa D. Foss
  5. Jonathon J. Stone
  6. Jonathan A. Runstadler

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Abstract

Ferrets have been demonstrated to be susceptible to laboratory infection of SARS-CoV-2, raising the possibility of natural transmission from humans into their pets in domestic settings. We demonstrate that ferrets may have host barriers that limit natural infection and transmission. First, we find no evidence of infection in 29 ferrets from a home with constant exposure to two adults with one confirmed and one suspected case of symptomatic COVID-19. Second, we analyze genetic sequences from viruses and hosts and demonstrate that ferrets have genetic factors that confer resistance to natural SARS-CoV-2 infection. These data suggest that ferret infection may require viral adaptation, and therefore ferrets may only be semipermissive models of SARS-CoV-2 disease or transmission.

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  1. Version published to 10.1073/pnas.2025601118
  2. ScreenIT

    SciScore for 10.1101/2020.08.21.254995: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Study enrollment and sample collection: The study participants were enrolled under a protocol approved by Tufts University Institutional and Animal Care and Use Committee and Health Sciences Institutional Review Board (#G2020-27).
    IRB: Study enrollment and sample collection: The study participants were enrolled under a protocol approved by Tufts University Institutional and Animal Care and Use Committee and Health Sciences Institutional Review Board (#G2020-27).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    To collect viral genomes from experimental ferret infection, sequencing reads were downloaded from 23 Illumina and Minion sequencing runs uploaded to NCBI Sequence Read Archive (PRJNA641813).
    Sequence Read Archive
    suggested: (DDBJ Sequence Read Archive, RRID:SCR_001370)
    Reads were confirmed to be post-quality control by Prinseq and mapped to the human donor sequence (hCoV-19/Germany/BavPat1/2020|EPI_ISL_406862|2020-01-28) using BWA (Illumina) and Pomoxis mini_align (Minion).
    Prinseq
    suggested: (PRINSEQ, RRID:SCR_005454)
    Mustela putorius furo orthologs were inconsistent with related species by preliminary RAxML ortholog analysis.
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    Seven publicly available RNAseq run from Mustela putorius furo (SRR11517721-SRR11517724, SRR391982, SRR391968, SRR391966) were downloaded and putative PCSK1-7/CTSL reads were extracted using BLAST.
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)
    Reads were then mapped back to the proposed ferret assembly with BWA and well-supported consensus sequences were called using Samtools.
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    These limitations and putative host-adaptations may negatively affect ferrets as a disease and/or transmission model and should be further investigated. We are, however, optimistic that the lack of spillover in this household supports that there is a very low risk of human-to-ferret SARS-CoV-2 transmission in domestic settings.

    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.

  3. Version published to 10.1101/2020.08.21.254995v2 on bioRxiv
  4. Version published to 10.1101/2020.08.21.254995v1 on bioRxiv