Blood group A enhances SARS-CoV-2 infection
Shang‐Chuen Wu, Connie M. Arthur, Hau-Ming Jan, Wilfredo F. García-Beltrán, Kashyap Patel, Matthew F. Rathgeber, Hans Verkerke, Narayanaiah Cheedarla, Ryan Philip Jajosky, Anu Paul, Andrew S. Neish, John D. Roback, Cassandra D. Josephson, Duane R. Wesemann, Daniel Kalman, Seth Rakoff-Nahoum, Richard D. Cummings, Sean R. Stowell
Abstract
Among the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ABO(H) blood group antigens are among the most recognized predictors of infection. However, the mechanisms by which 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. Because ABO(H) blood group antigens are carbohydrates, we compared the glycan-binding specificity of SARS-CoV-2 RBD with that of 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 also 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, whereas similar incubation with a galectin that does not recognize blood group antigens failed to impact SARS-CoV-2 infection. These results demonstrated that SARS-CoV-2 can engage blood group A, providing a direct link between ABO(H) blood group expression and SARS-CoV-2 infection.