Comparison of SARS-CoV-2 infections among 3 species of non-human primates

  1. Shuaiyao Lu
  2. Yuan Zhao
  3. Wenhai Yu
  4. Yun Yang
  5. Jiahong Gao
  6. Junbin Wang
  7. Dexuan Kuang
  8. Mengli Yang
  9. Jing Yang
  10. Chunxia Ma
  11. Jingwen Xu
  12. Xingli Qian
  13. Haiyan Li
  14. Siwen Zhao
  15. Jingmei Li
  16. Haixuan Wang
  17. Haiting Long
  18. Jingxian Zhou
  19. Fangyu Luo
  20. Kaiyun Ding
  21. Daoju Wu
  22. Yong Zhang
  23. Yinliang Dong
  24. Yuqin Liu
  25. Yingqiu Zheng
  26. Xiaochen Lin
  27. Li Jiao
  28. Huanying Zheng
  29. Qing Dai
  30. Qiangmin Sun
  31. Yunzhang Hu
  32. Changwen Ke
  33. Hongqi Liu
  34. Xiaozhong Peng

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Abstract

COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta , 6 Macaca fascicularis ) and New world monkeys (6 Callithrix jacchus ), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta , 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis , the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus.

One Sentence Summary

M. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus .

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  1. Version published to 10.1101/2020.04.08.031807v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.04.08.031807: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethics statement: All animal procedures were approved by the Institutional Animal Care and Use Committee of Institute of Medical Biology, Chinese Academy of Medical Science (Ethics number: DWSP202002 001), and performed in the ABSL-4 facility of Kunming National High-level Biosafety Primate Research Center, Yunnan
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Flow cytometric analysis was conducted on Cytoflex (Backman, USA) using florescent-labelled antibodies against cellular surface marker CD45, CD3, CD4, CD8, CD14.
    CD45
    suggested: None
    CD3
    suggested: None
    CD4
    suggested: None
    CD8
    suggested: None
    CD14
    suggested: None
    HRP-conjugated goat anti-human IgG (H+L) antibody was added to detect the captured spike-specific antibodies.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Viruses were amplified on Vero-E6 cells and concentrated by ultrafilter system via 300kDa module (Millipore).
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Localization of viral RNA in tissues: A novel nucleic acid hybridization technique RNAscope was performed to detect and localize viral RNA in paraffin-embedded tissue sections using SARS-CoV-2 specific probe (RNAscope® Probe-V-nCoV2019-S, ACD, Cat No. 848561, targeting the region of 21631 – 23303 (NC_045512.2) of SARS-CoV-2 genome).
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)
    Data was plotted via the software GraphPad.
    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.

  3. Version published to 10.1101/2020.04.08.031807v1 on bioRxiv