Use of convalescent serum reduces severity of COVID-19 in nonhuman primates

  1. Robert W. Cross
  2. Abhishek N. Prasad
  3. Viktoriya Borisevich
  4. Courtney Woolsey
  5. Krystle N. Agans
  6. Daniel J. Deer
  7. Natalie S. Dobias
  8. Joan B. Geisbert
  9. Karla A. Fenton
  10. Thomas W. Geisbert

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Abstract

No abstract available

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  1. Version published to 10.1016/j.celrep.2021.108837
  2. ScreenIT

    SciScore for 10.1101/2020.10.14.340091: (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 variableAnimal challenge: Prior to enrollment in this study, AGMs (Chlorocebus aethiops; n=10; 6 males, 4 females; St Kitts origin, Worldwide Primates, Inc.) were tested for sero-reactivity to SARS-CoV-2.
    Cell Line AuthenticationContamination: This isolate is certified mycoplasma and Foot-and-Mouth Disease virus free.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISA: SARS-CoV-2-specific IgG antibodies were measured in sera by ELISA at the indicated time points.
    ELISA: SARS-CoV-2-specific IgG
    suggested: None
    SARS-CoV-2-specific
    suggested: None
    After a one-hour incubation, plates were washed six times with wash buffer (1 x PBS with 0.2% Tween-20) and incubated for an hour with a 1:5000 dilution of horseradish peroxidase (HRP)-conjugated anti-primate IgG antibody (Fitzgerald Industries International; Cat: 43R-IG020HRP).
    anti-primate IgG
    suggested: None
    For IHC, specific anti-SARS immunoreactivity was detected using an anti-SARS nucleocapsid protein rabbit primary antibody at a 1:800 dilution for 60 minutes (Novusbio).
    anti-SARS
    suggested: None
    anti-SARS nucleocapsid protein
    suggested: None
    Secondary antibody used was biotinylated goat anti-rabbit IgG (Vector Laboratories) at 1:200 for 30 minutes followed by Vector Streptavidin Alkaline Phosphatase at a dilution of 1:200 for 20 min (Vector Laboratories).
    anti-rabbit IgG
    suggested: None
    For IHC, specific anti-fibrin was detected using an anti-fibrin monoclonal mouse primary antibody at a 1:3200 dilution for 60 minutes (Sekisui Diagnostics).
    anti-fibrin
    suggested: None
    Secondary antibody used was biotinylated goat anti-mouse IgG (Vector Laboratories) at 1:200 for 30 minutes followed by Vector Streptavidin Alkaline Phosphatase at a dilution of 1:200 for 20 min (Vector Laboratories).
    anti-mouse IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For in vivo challenge, the P2 virus was propagated on Vero E6 cells and the supernatant was collected and clarified by centrifugation making the virus used in this study a P3 stock.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Slides were developed with Bio-Red (Biopath Laboratories) for 7 minutes and counterstained with hematoxylin for one minute.
    Biopath
    suggested: None
    Statistical Analysis: The data was analyzed and graphed in GraphPad Prism 8.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Overall, the consensus of these studies is that therapeutic benefit is possible; however, a number of caveats associated with doing human studies including unknown incubation times, effective dose, and/or route(s) of exposure. These shortcomings highlight the need for experimentally-controlled studies to help understand potential risks of this approach. Others have demonstrated therapeutic benefit in rodent models of COVID-19 but limited information was gleaned in terms of the pathophysiological parameters impacted by treatment with CCP (Chan et al., 2020; Imai et al., 2020). While hyper-immune plasma has been shown to provide therapeutic benefit in related MERS-CoV-infected primates (van Doremalen et al., 2017), to date, there are no reports demonstrating convalescent sera or plasma treatment benefit in NHP models of COVID-19. Here, we provide evidence that convalescent sera with high neutralizing antibody titers can be given as a postexposure treatment using a NHP model which faithfully recapitulates hallmark features of human COVID-19. Compared to LD-treated or untreated control animals, HD-treated AGMs had lower viral burdens in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several clinical parameters previously shown to be important in human disease including: pro-longed coagulation times, elevated fibrinogen, thrombocytopenia, and hypercytokinemia. Differences in clinical parameters of the LD-treated group ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We 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 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 10.1101/2020.10.14.340091v1 on bioRxiv