Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

  1. Bas B. Oude Munnink
  2. Reina S. Sikkema
  3. David F. Nieuwenhuijse
  4. Robert Jan Molenaar
  5. Emmanuelle Munger
  6. Richard Molenkamp
  7. Arco van der Spek
  8. Paulien Tolsma
  9. Ariene Rietveld
  10. Miranda Brouwer
  11. Noortje Bouwmeester-Vincken
  12. Frank Harders
  13. Renate Hakze-van der Honing
  14. Marjolein C. A. Wegdam-Blans
  15. Ruth J. Bouwstra
  16. Corine GeurtsvanKessel
  17. Annemiek A. van der Eijk
  18. Francisca C. Velkers
  19. Lidwien A. M. Smit
  20. Arjan Stegeman
  21. Wim H. M. van der Poel
  22. Marion P. G. Koopmans

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus—one that spilled over from another species to infect and transmit among humans. We know that humans can infect other animals with SARS-CoV-2, such as domestic cats and even tigers in zoos. Oude Munnink et al. used whole-genome sequencing to show that SARS-CoV-2 infections were rife among mink farms in the southeastern Netherlands, all of which are destined to be closed by March 2021 (see the Perspective by Zhou and Shi). Toward the end of June 2020, 68% of mink farm workers tested positive for the virus or had antibodies to SARS-CoV-2. These large clusters of infection were initiated by human COVID-19 cases with viruses that bear the D614G mutation. Sequencing has subsequently shown that mink-to-human transmission also occurred. More work must be done to understand whether there is a risk that mustelids may become a reservoir for SARS-CoV-2.

Science , this issue p. 172 ; see also p. 120

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  1. ScreenIT

    SciScore for 10.1101/2020.09.01.277152: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The resulting raw sequence data was demultiplexed using Porechop (https://github.com/rrwick/Porechop).
    Porechop
    suggested: (Porechop, RRID:SCR_016967)
    Phylogenetic analysis: All available near full-length Dutch SARS-CoV-2 genomes available on 1st of July were selected (n=1,775) and aligned with the sequences from this study using MUSCLE (45).
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    The phylogenetic trees were visualized in Figtree (http://tree.bio.ed.ac.uk/software/figtree/).
    Figtree
    suggested: (FigTree, RRID:SCR_008515)
    A custom R script was used to distinguish synonymous from non-synonymous mutations and non-synonymous mutations were visualized using a tile map from the ggplot2 package (48).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Maps were created using R packages sp (50), raster (51) and rgdal (52) and ArcGIS 10.6 software by ESRI.
    ArcGIS
    suggested: (ArcGIS for Desktop Basic, RRID:SCR_011081)

    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 10.1126/science.abe5901
  3. NCRC

    Our take

    In this preprint that has not yet been peer-reviewed, the authors detailed the occurrence of SARS-CoV-2 in animals and humans on 16 mink farms in the Netherlands. The timing of outbreaks in animals relative to human cases, along with viral genome sequencing, provides evidence of transmission from humans to mink and vice versa, and multiple independent introductions of viral phylogenetic groups across farms. Countries with mink farms (or other carnivore farms), including Denmark, Spain, the US, and China, should monitor animals and workers for SARS-CoV-2 to prevent large outbreaks and the possibility of viral persistence in carnivore populations.

    Study design

    ecological;other

    Study population and setting

    This paper summarizes epidemiological investigations of SARS-CoV-2 outbreaks on 16 mink (Neovison vison) farms in the Netherlands between April and June 2020. The first outbreaks occurred on April 23 and April 25, 2020, after which the Dutch Minister of Agriculture implemented a surveillance system for SARS-Cov-2, involving weekly testing of dead animals and full investigation of outbreaks, and ordered all animals on infected mink farms to be culled. Workers on infected farms were tested by PCR or serology within days of the first diagnosis of infection in animals. Full investigations included whole genome sequencing of SARS-CoV-2 from infected animals and farm workers and tracing contacts with other farms that could have led to virus introduction, including movement of vehicles, workers, equipment, manure, or food. A total of 97 farm workers were tested for evidence of infection with the virus via PCR or serological assays. To assess the potential sources of the virus on the infected farms, the authors included 1,775 reference SARS-CoV-2 genomes from a national database, and 34 from anonymized COVID-19 patients in the same postal codes as farms in March and April. Additional genomes (N = 65) from COVID-19 cases in Poland were included because many seasonal workers on the farms come from Poland.

    Summary of main findings

    Screening of farm workers at 16 farms showed that 66/97 (67%) of individuals had evidence of SARS-CoV-2 infection either via PCR or serology. In most cases, virus genomes from human workers clustered phylogenetically with genomes from mink on the same. SARS-CoV-2 viruses grouped into five different phylogenetic clusters with outbreaks on farms having infections of one, or in one case two, virus groups. Such patterns imply that outbreaks on farm were largely from separate introductions and not due to transmission between farms. On two farms (NB1 and NB2), the timing of infections suggest that infected workers first introduced the virus to animals. On farms NB3 and NB7, workers became infected with SARS-CoV-2 only after the virus was spreading in the mink populations on the farms, suggesting that the human cases resulted from transmission from mink. Comparison of sequences from mink and mink farm workers to SARS-CoV-2 genomes from patients across the Netherlands (N = 1,775), from cases nearby to the first four farms (N = 34) and sequences from Poland (N = 65) showed that none were related to the mink farm outbreaks. Additionally, the presence of viral groups across different farms could not be explained by common ownership, shared personnel, feed supplier, veterinary service provider, or geographic distance.

    Study strengths

    The study benefited from the simultaneous or retrospective testing of both human workers and mink on each farm. Full genome sequencing increased the phylogenetic resolution for assessing relatedness between viruses infecting mink and humans. Including reference sequence from COVID-19 cases in the Netherlands and from elsewhere in Europe were important for understanding how outbreaks on farms began.

    Limitations

    The authors did not provide details on the number of animals that became ill or died from SARS-CoV-2 on each farm, or the prevalence of infection by PCR testing. Thus, we cannot determine any epidemiological parameters for the virus in mink (e.g., R0, infection fatality rate). The limited number of viral genomes that were used for comparison with viruses on each farm may explain their inability to determine the broader origin of outbreaks on farms. Limited testing in the Netherlands also means that spillback into the wider community from infected mink farms cannot be ruled out, even though it was not observed in these data. Lastly, interviews identified that some temporary workers were not included in testing and were lost to follow-up, so it cannot be ruled out that these workers may have partly contributed to virus introduction on farms, along with the permanent employees.

    Value added

    This report provides additional information on the outbreaks of SARS-CoV-2 on mink farms in the Netherlands, particularly the first evidence of an outbreak of SARS-CoV-2 in non-human animals and of animal-to-human transmission of SARS-CoV-2.

  4. ScreenIT

    SciScore for 10.1101/2020.09.01.277152: (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

    Antibodies
    SentencesResources
    All samples from the 8 employees taken on April 30th were negative by RT-PCR but tested positive for SARS-CoV-2 antibodies.
    SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    hCov−19/Netherlands/NB9_Mink_1 C V R L H I C V R L H I hCov−19/Netherlands/NoordBrabant_178/2020 C V R L H C I I L T L I F K C I F K C I K C I K C I M Q I G Q I G Q L G L G E L C G E L C G 25 62 115 G C 38 45 C L 32 34 55 57 182 207 219 224 229 258 L E 11 187 314 794 1003 1092 1179 1181 1315 1369 1637 1681 1882 2025 2143 2222
    G 25
    suggested: None
    Software and Algorithms
    SentencesResources
    The resulting raw sequence data was demultiplexed using Porechop (https://github.com/rrwick/Porechop).
    Porechop
    suggested: (Porechop, RRID:SCR_016967)
    Phylogenetic analysis All available near full-length Dutch SARS-CoV-2 genomes available on 1st of July were selected (n=1,775) and aligned with the sequences from this study using MUSCLE (45).
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    The phylogenetic trees were visualized in Figtree (http://tree.bio.ed.ac.uk/software/figtree/).
    Figtree
    suggested: (FigTree, RRID:SCR_008515)
    A custom R script was used to distinguish synonymous from non-synonymous mutations and non-synonymous mutations were visualized using a tile map from the ggplot2 package (48).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Maps were created using R packages sp (50), raster (51) and rgdal (52) and ArcGIS 10.6 software by ESRI.
    ArcGIS
    suggested: (ArcGIS for Desktop Basic, RRID:SCR_011081)
    From 2 samples WGS could be generated from the employees which clustered together with the sequences from the animals from this farm.
    WGS
    suggested: None

    Results from OddPub: Thank you for sharing your code.

    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.

    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.

  5. Version published to 10.1101/2020.09.01.277152v1 on bioRxiv