Blood group A enhances SARS-CoV-2 infection.

Area of Science:

• Virology
• Immunology
• Glycobiology

Background:

• ABO(H) blood group antigens are recognized risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Mechanisms linking ABO(H) antigens to COVID-19 susceptibility are not fully understood.
• The SARS-CoV-2 receptor-binding domain (RBD) shares similarities with galectins, which are carbohydrate-binding proteins.

Purpose of the Study:

• To investigate the glycan-binding specificity of SARS-CoV-2 RBD.
• To compare SARS-CoV-2 RBD binding with that of galectins.
• To elucidate the role of ABO(H) blood group antigens in SARS-CoV-2 infection.

Main Methods:

• Utilized glycan array analysis to compare binding profiles of SARS-CoV-2 RBD and galectins.
• Assessed the infectivity of SARS-CoV-2 variants (including Delta and Omicron) on blood group A-expressing cells.
• Investigated the inhibitory effect of galectins on SARS-CoV-2 infection of blood group A cells.

Main Results:

• SARS-CoV-2 RBD, including Delta and Omicron variants, demonstrated specificity for blood group A.
• SARS-CoV-2 viruses showed a preferential ability to infect blood group A-expressing cells.
• A blood group-binding galectin inhibited SARS-CoV-2 infection enhancement in blood group A cells, while a non-binding galectin did not.

Conclusions:

• SARS-CoV-2 directly engages blood group A antigens.
• This binding provides a direct mechanistic link between ABO(H) blood group expression and SARS-CoV-2 infection susceptibility.
• The findings offer insights into host-pathogen interactions in COVID-19.