Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2

  1. Linlin Bao
  2. Wei Deng
  3. Hong Gao
  4. Chong Xiao
  5. Jiayi Liu
  6. Jing Xue
  7. Qi Lv
  8. Jiangning Liu
  9. Pin Yu
  10. Yanfeng Xu
  11. Feifei Qi
  12. Yajin Qu
  13. Fengdi Li
  14. Zhiguang Xiang
  15. Haisheng Yu
  16. Shuran Gong
  17. Mingya Liu
  18. Guanpeng Wang
  19. Shunyi Wang
  20. Zhiqi Song
  21. Ying Liu
  22. Wenjie Zhao
  23. Yunlin Han
  24. Linna Zhao
  25. Xing Liu
  26. Qiang Wei
  27. Chuan Qin

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection.

One Sentence Summary

Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.03.13.990226: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementAll animal procedures and experiments were carried out in accordance with the protocols approved by the Institutional Animal Care and Use Committee ( IACUC ) of the Institute of Laboratory Animal Science , Chinese Academy of Medical Sciences ( BLL20001) .Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    , Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications . medRxiv , 2020.2003.2030.20047365 ( 2020) . 7 . N . M. A . OKBA et al. , SARS-CoV-2 specific antibody responses in COVID-19 patients . medRxiv , 2020.2003.2018.20038059 ( 2020) . 8 . K . K . To et al. , Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study .
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)
    At http://www.nhc.gov.cn/yzygj/s7652m/202002/54e1ad5c2aac45c19eb541799bf637e9.shtml. 15 . S. F . Wang et al. , Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins .
    Antibody-dependent SARS
    suggested: None
    1:100 diluted sera were added to each well and incubated for 30 minutes at 37°C , followed by the HRP-labeled goat anti-monkey antibody ( Abcam , ab112767 ) incubated for 30 minutes at room temperature.
    anti-monkey
    suggested: None
    After blocking in 1 % normal goat serum for 1 hour at room temperature , the sections were stained with 7D2 monoclonal antibody ( 1:500 dilution , laboratory preparation ) and CD68 antibody ( 1:500 dilution , Abcam , ab201340 ) at 4°C overnight , following with the incubation of HRP-labeled goat anti-mouse IgG ( Beijing ZSGB Biotechnology , ZDR-5307 ) for 1 hour .
    CD68
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>anti-mouse IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Alternatively , the sections were stained with CK7 antibody ( 1:1000 dilution , Abcam , ab181598)</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CK7</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">, CD4 antibody ( 1:500 dilution , Beijing ZSGB Biotechnology)</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CD4</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">, CD8 antibody ( 1:200 dilution , Abcam , ab4055)</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CD8</b></div>
        <div>suggested: (Abcam Cat# ab4055, <a href="https://scicrunch.org/resources/Any/search?q=AB_304247">AB_304247</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">CD20 antibody ( 1:500 dilution , Abcam , ab78237 ) or CD138 antibody ( 1:500 dilution , Abcam , ab128936 ) at 4℃ overnight , followed by HRP-labeled goat anti-rabbit IgG secondary antibody ( Beijing ZSGB Biotechnology , PV9001 ) for 60 min .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CD20</b></div>
        <div>suggested: (Abcam Cat# ab78237, <a href="https://scicrunch.org/resources/Any/search?q=AB_1640323">AB_1640323</a>)</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>CD138</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>HRP-labeled goat</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>IgG secondary antibody ( Beijing ZSGB Biotechnology , PV9001 ) for 60 min</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Neutralizing antibody assay Sera samples were tested for the presence of neutralizing antibody observed by cytopathic effect ( CPE) .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CPE</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Experimental Models: Cell Lines</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Then , serially two-fold diluted sera were incubated with 100 TCID50 SARS-CoV-2 for 1 h at 37°C , and added into Vero-E6 cells in a 96-well-plate.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Vero-E6</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Lu et al. , Comparison of SARS-CoV-2 infections among 3 species of non-human primates . bioRxiv , 2020.2004.2008.031807 ( 2020) . 10 . V . J . Munster et al. , Respiratory disease and virus shedding in rhesus macaques inoculated with SARS-CoV-2 . bioRxiv , 2020.2003.2021.001628 ( 2020) . 11</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>bioRxiv</b></div>
        <div>suggested: (bioRxiv, <a href="https://scicrunch.org/resources/Any/search?q=SCR_003933">SCR_003933</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">All data were analyzed with GraphPad Prism 8.0 software.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>GraphPad Prism</b></div>
        <div>suggested: (GraphPad Prism, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002798">SCR_002798</a>)</div>
      </div>
    </td></tr></table>

    Results from Barzooka: We also found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.03.13.990226v2 on bioRxiv
  3. Version published to 10.1101/2020.03.13.990226v1 on bioRxiv