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. 2023 Jun 27. Online ahead of print. doi: 10.1182/blood.2022018903

Blood Group A Enhances SARS-CoV-2 Infection

Shang-Chuen Wu 1, Connie M Arthur 1, Hau-Ming Jan 1, Wilfredo F Garcia-Beltran 2, Kashyap R Patel 1, Matthew F Rathgeber 1, Hans P Verkerke 1,3, Narayanaiah Cheedarla 3, Ryan Philip Jajosky 1, Anu Paul 1, Andrew S Neish 4, John D Roback 3,4, Cassandra D Josephson 5, Duane R Wesemann 6, Daniel Kalman 4, Seth Rakoff-Nahoum 7, Richard D Cummings 8, Sean R Stowell 1,
PMCID: PMC10294591  PMID: 37367252

Abstract

Among risk factors for SARS-CoV-2, ABO(H) blood group antigens have been one of the most recognized predictors of infection. However, the mechanisms whereby ABO(H) antigens influence susceptibility to COVID-19 remain incompletely understood. The receptor binding domain (RBD) of SARS-CoV-2, which facilitates host cell engagement, bears significant similarity to galectins, an ancient family of carbohydrate binding proteins. As ABO(H) blood group antigens are carbohydrates, we compared the glycan binding specificity of the SARS-COV-2 RBD with galectins. Similar to the binding profile of several galectins, the RBDs of SARS-CoV-2, including Delta and Omicron variants, exhibited specificity for blood group A. Not only did each RBD recognize blood group A in a glycan array format, but each SARS-CoV-2 virus likewise displayed a preferential ability to infect blood group A expressing cells. Preincubation of blood group A cells with a blood group binding galectin specifically inhibited the blood group A enhancement of SARS-CoV-2 infection, while similar incubation with a galectin that does not recognize blood group antigens failed to impact SARS-CoV-2 infection. These results demonstrate that SARS-CoV-2 can engage blood group A, providing a direct link between ABO(H) blood group expression and SARS-CoV-2 infection.

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Data Sharing: All reagents will be made upon email request

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Supplemental Figure, Methods and References

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Supplementary Materials

Supplemental Figure, Methods and References

Articles from Blood are provided here courtesy of Elsevier

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