COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions

  1. Opeyemi S. Adeniji
  2. Leila B. Giron
  3. Netanel F Zilberstein
  4. Maliha W. Shaikh
  5. Robert A Balk
  6. James N Moy
  7. Christopher B. Forsyth
  8. Ali Keshavarzian
  9. Alan Landay
  10. Mohamed Abdel-Mohsen

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Abstract

Beyond neutralization, antibodies elicit several innate immune functions including complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). These functions can be both beneficial (by clearing pathogens) and/or detrimental (by inducing inflammation). We tested the possibility that qualitative differences in SARS-CoV-2 specific antibody-mediated innate immune functions contribute to Coronavirus disease 2019 (COVID-19) severity. We found that antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from non-hospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 antibodies as potential contributors to COVID-19 severity.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.11.426209: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: All research protocols of the study were approved by the institutional review boards (IRB) at Rush University and The Wistar Institute.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe cohort was also chosen to be 45–60% female per group.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ADCD measurements: Purified IgG antibodies were analyzed for their ability to fix complement on target cells.
    Purified IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    4 × 106 (ACE2)-CHO cells were pulsed with 20 μg biotinylated SARS-CoV-2 S1 or RBD proteins (Acro Biosystems) for 30 min at 37°C.
    ACE2)-CHO
    suggested: None
    A 200 μl suspension of THP-1 cells at 2.5 × 105 cells/ml was added to each well, for a total of 5 × 104 THP-1 cells per well.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    Cells were analyzed by flow cytometry, and data collected were analyzed in FlowJo software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analyses were performed in Prism 7.0 (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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.

  2. Version published to 10.1101/2021.01.11.426209 on bioRxiv