ABO and COVID-19 susceptibility: A role for ABH glycans and ABO antibodies?
Bruce Motyka1,2,3,4, Anne Halpin1,2,3,4,5,6, Caishun Li1,2,3,4, Tess Ellis1,2,3,4, Jean Pearcey1,2,3,4, Roger Bascom1,2,3,4, Linh Nguyen3,7, John Klassen3,7, Matthew S Macauley3,7, Todd L Lowary3,7,8, Shang-Te D Hsu8, Jayan Nagendran1,2,9, Marcelo Cypel2,10, Don D Sin11, Andrew Lane12, Avi Z Rosenberg12, Lori J West1,2,3,4,5,9,13.
1Alberta Transplant Institute, University of Alberta, Edmonton, AB, Canada; 2Canadian Donation and Transplantation Research Program, University of Alberta, Edmonton, AB, Canada; 3Canadian Glycomics Network, University of Alberta, Edmonton, AB, Canada; 4Dept of Pediatrics, University of Alberta, Edmonton, AB, Canada; 5Dept of Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB, Canada; 6Alberta Precision Laboratories, University of Alberta Hospital, Edmonton, AB, Canada; 7Dept of Chemistry, University of Alberta, Edmonton, AB, Canada; 8Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; 9Dept of Surgery, University of Alberta, Edmontonc, AB, Canada; 10University of Toronto, Toronto, ON, Canada; 11University of British Columbia, Vancouver, BC, Canada; 12Johns Hopkins School of Medicine, Baltimore, MD, United States; 13Dept of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, Canada
Introduction: Population-based and GWAS studies have reported an association between ABO blood group and SARS-CoV-2 susceptibility, with ABO blood group A (ABO-A) individuals relatively more susceptible than other ABO-groups, and ABO-O individuals relatively protected. We aimed to define possible roles of ABH glycans and ABO antibodies in susceptibility to SARS-CoV-2 infection.
Methods: I) We examined the ABH glycan decoration of lung and nasal tissue from individuals of known ABO blood groups by immunohistochemistry using a panel of monoclonal antibodies to ABH glycan subtype antigens. II) We investigated ABH glycan binding properties of the SARS-CoV-2 receptor binding domain (RBD) protein using electrospray ionization mass spectrometry (ESI-MS). III) We measured ABO antibodies (isotype and ABH glycan subtype-specificity) in ABO-O COVID-19 hospitalized patients (n=50) and healthy controls (pre-COVID vaccination, n=73) with a novel Luminex bead-based assay.
Results: I) Tissue ABH: In ABO-A individuals, upper (sustentacular cells) and lower airway epithelial cells were found to be decorated with A-subtype II and III/IV glycans, but lung endothelium was decorated with only A-subtype II glycans. ABO-A-glycans on lung epithelial and endothelial cells were co-localized with ACE2 (Fig. 1A-C). II) Glycan binding: A-glycans bound RBD protein (Fig. 2). III) ABO antibodies: In ABO-O individuals, IgM anti-A antibodies specific for subtypes II-IV, and IgG anti-A antibodies specific to subtype IV were significantly lower in individuals with COVID-19 compared to healthy controls (Fig. 3).
Conclusion: Expression of tissue A-glycans and their co-localization with ACE2 in airway epithelial cells of ABO-A individuals, together with their ability to bind spike RBD proteins, are consistent with a possible viral co-receptor role, as described for other viruses. This could enhance infection susceptibility in ABO-A individuals. We have previously shown that healthy ABO-O individuals have a wide range of anti-A antibody levels (IgG, IgM) and thus cannot be categorized into one risk group. This heterogeneity is likely of key importance in understanding the population-level association between ABO-O blood group and the lower risk of COVID-19 infection. Our preliminary data support the hypothesis that ABO-O individuals with lower levels of anti-A antibodies, perhaps of a particular subtype-specificity and/or isotype, may be at higher risk of infection than ABO-O individuals with more abundant anti-A antibodies.
This work was supported through the Canadian Institutes of Health Research and the Women and Children's Health Research Institute / Stollery Children's Hospital Foundation..
Lectures by Anne M Halpin
| When | Session | Talk Title | Room |
|---|---|---|---|
|
Sun-30 16:40 - 18:00 |
Abstracts Session 1 | ABO and COVID-19 susceptibility: A role for ABH glycans and ABO antibodies? | Grand Georgian |
|
Mon-01 09:20 - 10:20 |
Abstracts Session 2 | IgG and IgM ABO antibodies detected by a novel bead-based assay fail to be discriminated by hemagglutination methods | Grand Georgian |