The antibody response to the glycan α‐Gal correlates with COVID‐19 disease symptoms

  1. José Miguel Urra
  2. Elisa Ferreras‐Colino
  3. Marinela Contreras
  4. Carmen M. Cabrera
  5. Isabel G. Fernández de Mera
  6. Margarita Villar
  7. Alejandro Cabezas‐Cruz
  8. Christian Gortázar
  9. José de la Fuente

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Abstract

The coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has affected millions of people worldwide. Characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to progress in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Galα1‐3Galβ1‐(3)4GlcNAc‐R (α‐Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti‐α‐Gal immunoglobulin M (IgM)/IgG antibodies produced in response to bacterial microbiota. In addition to anti‐α‐Gal antibody‐mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to α‐Gal may contribute to the control of COVID‐19. To address this hypothesis, we characterized the antibody response to α‐Gal in patients at different stages of COVID‐19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti‐SARS‐CoV‐2 (Spike) IgG antibody titers increased, reduction in anti‐α‐Gal IgE, IgM, and IgG antibody titers and alteration of anti‐α‐Gal antibody isotype composition correlated with COVID‐19 severity. The results suggested that the inhibition of the α‐Gal‐induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α‐Gal epitopes to modify the microbiota and increase α‐Gal‐induced protective immune response and reduce severity of COVID‐19.

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  1. Version published to 10.1002/jmv.26575
  2. ScreenIT

    SciScore for 10.1101/2020.07.14.201954: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The use of samples and individual’s data was approved by the Ethical and Scientific Committee (University Hospital of Ciudad Real, C-352 and SESCAM C-73). 2.2.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Samples from asymptomatic COVID-19 cases with positive anti-SARS-CoV-2 IgG antibody titers but negative by RT-PCR (n = 10) were collected in May 22-29, 2020 and included in the analysis.
    anti-SARS-CoV-2 IgG
    suggested: None
    Determination of antibody titers against SARS-CoV-2: Antibody titers specific for the recognition of virus infection based on IgG against SARS-CoV-2 Spike (EI 2606-9601 G) and Nucleocapsid (EI 2606-9601-2 G) proteins and IgA (EI 2606-9601 A) were determined by ELISA (Euroimmun, Lubeck, Germany) following manufacturer’s indications [19,20].
    SARS-CoV-2
    suggested: None
    Plates were washed four times with PBST and 100 μl/well of goat anti-human immunoglobulins-peroxidase IgG (FC specific; Sigma-Aldrich), IgM (μ-chain specific; Sigma-Aldrich), IgE (ɛ-chain specific; Sigma-Aldrich), and IgA (heavy chain specific; Bio-Rad, Hercules, CA, USA) secondary antibodies diluted 1:1000, v/v in blocking solution were added and incubated for 1 h at RT.
    anti-human immunoglobulins-peroxidase IgG
    suggested: None
    IgA
    suggested: None
    Reference values for serum immunoglobulin levels [21] were considered in the analysis of the profile of anti-α-Gal antibody isotypes. 2.5.
    anti-α-Gal
    suggested: None
    A Spearman Rho (rs) correlation analysis (p = 0.05; https://www.socscistatistics.com/tests/spearman/default2.aspx) was conducted between anti-SARS-CoV-2 Spike IgG titers and COVID-19 disease severity (2 = asymptomatic, 3 = hospital discharge, 4 = hospitalized, 5 = ICU), anti-α-Gal IgA, IgE, IgM and IgG antibody titers and disease severity (1 = healthy, 2 = asymptomatic, 3 = hospital discharge, 4 = hospitalized, 5 = ICU), and for anti-α-Gal IgA and IgG antibody titers between serum and saliva samples.
    COVID-19 disease severity (2 = asymptomatic, 3
    suggested: None
    anti-α-Gal IgA, IgE, IgM and IgG
    suggested: None
    anti-α-Gal IgA
    suggested: None
    IgG antibody titers between serum and saliva
    suggested: None
    Software and Algorithms
    SentencesResources
    The infection by SARS-CoV-2 was confirmed in all patients included in the study by the real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay from Abbott Laboratories (Abbott RealTime SARS-COV-2 assay, Abbott Park, Illinois, USA) from upper respiratory tract samples after hospital admission.
    Abbott Laboratories
    suggested: None

    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

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  3. Version published to 10.1101/2020.07.14.201954 on bioRxiv