Abnormal antibodies to self-carbohydrates in SARS-CoV-2 infected patients

This article has been Reviewed by the following groups

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Abstract

SARS-CoV-2 is a deadly virus that is causing the global pandemic coronavirus disease 2019 (COVID-19). Our immune system plays a critical role in preventing, clearing, and treating the virus, but aberrant immune responses can contribute to deleterious symptoms and mortality. Many aspects of immune responses to SARS-CoV-2 are being investigated, but little is known about immune responses to carbohydrates. Since the surface of the virus is heavily glycosylated, pre-existing antibodies to glycans could potentially recognize the virus and influence disease progression. Furthermore, antibody responses to carbohydrates could be induced, affecting disease severity and clinical outcome. In this study, we used a carbohydrate antigen microarray with over 800 individual components to profile serum anti-glycan antibodies in COVID-19 patients and healthy control subjects. In COVID-19 patients, we observed abnormally high IgG and IgM antibodies to numerous self-glycans, including gangliosides, N -linked glycans, LacNAc-containing glycans, blood group H, and sialyl Lewis X. Some of these anti-glycan antibodies are known to play roles in autoimmune diseases and neurological disorders, which may help explain some of the unusual and prolonged symptoms observed in COVID-19 patients. The detection of antibodies to self-glycans has important implications for using convalescent serum to treat patients, developing safe and effective SARS-CoV-2 vaccines, and understanding the risks of infection. In addition, this study provides new insight into the immune responses to SARS-CoV-2 and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses.

Article activity feed

  1. SciScore for 10.1101/2020.10.15.341479: (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 variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The bound serum antibodies were detected by incubating with Cy3 anti-Human IgG and DyLight 647 anti-human IgM (Jackson ImmunoResearch) at 3 µg/mL in PBS buffer with 3% BSA and 1% HSA (100 µL/well) under agitation at 37 °C for 2 hours.
    anti-Human IgG
    suggested: None
    anti-human IgM
    suggested: None
    Each of the antibody stocks (PGT121, PGT126, PGT128, NIH AIDS Reagent Program) were diluted to 100 µg/mL diluted 5-fold in 1% BSA in PBS buffer.
    PGT121
    suggested: (bNAber Cat# bNAberID_24, RRID:AB_2491041)
    PGT126, PGT128
    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: We detected the following sentences addressing limitations in the study:
    Several limitations of this study should be mentioned. First, our glycan microarray only contains a small portion of the glycans found in the human glycome. Thus, there may be other important anti-glycan antibody populations that were not detected. Second, our study included a relatively small cohort of 40 COVID-19 patients and 20 healthy controls. In other work, we have profiled serum anti-glycan antibodies in hundreds of healthy subjects, so our understanding of normal antibody repertoires draws from considerable experience.56, 87 In contrast, these are the first 40 COVID-19 patients we have evaluated, and additional testing will be helpful to more fully investigate the findings in this study. Third, information about patient symptoms and outcome were not available. Consequently, follow up studies will be needed to evaluate potential correlations between symptoms and anti-glycan antibody repertoires. Additional studies to address these limitations are currently underway. Lastly, our study highlights the importance of studying immune responses to carbohydrates. Glycans are one of the major families of antigens found on SARS-CoV-2 and other viruses, but responses to these antigens are often difficult to study. By profiling serum antibodies with a large and diverse carbohydrate antigen microarray, we were able to rapidly identify abnormally high antibodies to a variety of self-glycans. These results provide new insight into the immune response to SARS-CoV-2 and illustrate the ...

    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.