No Evidence for Human Monocyte-Derived Macrophage Infection and Antibody-Mediated Enhancement of SARS-CoV-2 Infection

  1. Obdulio García-Nicolás
  2. Philip V’kovski
  3. Ferdinand Zettl
  4. Gert Zimmer
  5. Volker Thiel
  6. Artur Summerfield

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Abstract

Vaccines are essential to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and to protect the vulnerable population. However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. The potential infection of Fc receptor bearing cells such as macrophages, would support continued virus replication and inflammatory responses, and thereby potentially worsen the clinical outcome of COVID-19. Here we demonstrate that SARS-CoV-2 and SARS-CoV neither infect human monocyte-derived macrophages (hMDM) nor induce inflammatory cytokines in these cells, in sharp contrast to Middle East respiratory syndrome (MERS) coronavirus and the common cold human coronavirus 229E. Furthermore, serum from convalescent COVID-19 patients neither induced enhancement of SARS-CoV-2 infection nor innate immune response in hMDM. Although, hMDM expressed angiotensin-converting enzyme 2, no or very low levels of transmembrane protease serine 2 were found. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.

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  1. Version published to 10.3389/fcimb.2021.644574
  2. ScreenIT

    SciScore for 10.1101/2020.12.22.423940: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The use of buffy coats was approved by the SRC review board.
    Consent: For this study an informed consent and ethical approval was not needed because only leftovers of serum samples for diagnostic laboratory procedures were used.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    2.2 Cells: Vero cells (E6 and B4 lineages, African Green monkey kidney epithelial cells) and Huh-7 cells (human hepatocellular carcinoma cells) were cultured in Dulbecco’s minimal essential medium (DMEM; Life Technologies), supplemented with 10 % fetal bovine serum (
    Vero
    suggested: None
    Huh-7
    suggested: None
    MERS-CoV was propagated in Vero B4 cells in MEM supplemented with 2% of FBS and non-essential amino acids at 37°C.
    Vero B4
    suggested: CCLV Cat# CCLV-RIE 1146, RRID:CVCL_1912)
    Following an incubation period of 24 h, macrophages and Vero E6 cells were analyzed by flow cytometry for SARS-CoV-2 and SARS-CoV nucleocapsid (N) protein expression.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Finally, the percentage of infected hMDM was determined by by enumeratingof dsRNA positive cells in 10 fields/well using an Axio Observer Z1 inverted microscope equipped with a Zeiss Colibri Illuminator (CarlZeiss) and digital imaging Zeiss software (AxioVision, v4).
    Colibri Illuminator
    suggested: None
    AxioVision
    suggested: (AxioVision Imaging System, RRID:SCR_002677)
    All generated images were analyzed using ImageJ software.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    For analysis, Flowjo V.9.1 software (Treestars, Inc.) was used.
    Flowjo
    suggested: (FlowJo, RRID:SCR_008520)
    Detection limits were 30 pg/ml for TNF, 10 pg/ml for IFN-β, 4 pg/ml for IL-1β and 9 pg/ml for IL-6. 2.7 Statistics: For the generation of figures and data analyses the GraphPad Prism 8 Software (GraphPad Software, Inc.) was employed.
    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.
    • No funding statement was detected.
    • 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 10.1101/2020.12.22.423940v1 on bioRxiv