| Proposed mechanisms for association between ABO blood type and SARS‐CoV‐2 infection |
| Anti‐A and/or anti‐B antibodies serve as viral neutralizing antibodies by binding to A and/or B antigens expressed on the viral envelope, thereby preventing infection of target cells |
| The SARS‐CoV‐2 S protein is bound by human anti‐A antibodies, which may block the interaction between the virus and ACE2R, thereby preventing entry into the lung epithelium |
| An increase in ACE‐1 activity in group A individuals predisposes to cardiovascular complications, accounting for severe COVID‐19 |
| Variation of VWF and Factor VIII levels by ABO type with higher levels in group A individuals contributing to risk of thromboembolic disease and severe COVID‐19 |
| ABH glycans, if present on SARS‐CoV‐2 S protein, may modify the affinity of SARS‐CoV‐2 for ACE2R, its cellular receptor. |
| ABH glycans on target cells could serve as alternative, lower‐affinity receptors for SARS‐CoV‐2 S protein or bind other viral envelope structures. |
| Suggested experiments to confirm the proposed associations between ABO blood groups and SARS‐CoV‐2 infection |
| In vitro production of recombinant SARS‐CoV‐2 S protein in cell lines that can synthesize ABH glycans to determine whether these are, indeed, on the recombinant protein. |
| Culturing SARS‐CoV‐2 in cell lines capable of synthesizing ABH glycans, isolating the virus and determining whether anti‐A and anti‐B prevent infection of cell lines that do not express the corresponding ABH antigen. These experiments would also allow testing whether IgM and IgG anti‐A (or anti‐B) antibodies were equally effective. |
| Producing recombinant SARS‐CoV‐2 S protein in identical host cell lines (e.g. by transfecting in the relevant glycosyltransferases) and then quantifying the affinity of the purified proteins for their receptor. This can determine if ABH glycans are present on SARS‐CoV‐2 S protein and if they modify the affinity of SARS‐CoV‐2 for ACE2R. |
| Produce SARS‐CoV‐2 in vitro in ABH‐expressing cell lines; and quantify the infectivity of a given target cell line with purified virus. |
| Quantify IgA anti‐A and/or anti‐B and correlate with risk of susceptibility to infection by SARS‐CoV‐2 and severity COVID‐19 illness. |
Source:
ABO blood group and COVID‐19: a review on behalf of the ISBT COVID‐19 working group
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