Blood Group A Enhances SARS-CoV-2 Infection

• Type of Material: Article
• Authors: Shang-Chuen Wu, Harvard Medical School; Connie M. Arthur, Harvard Medical School; Hau-Ming Jan, Harvard Medical School; Wilfredo F. Garcia-Beltran, Harvard Medical School; Kashyap R. Patel, Harvard Medical School; Matthew F. Rathgeber, Harvard Medical School; Hans Verkerke, Emory University; Narayanaiah Cheedarla, Emory University; Ryan Philip Jajosky, Harvard Medical School; Anu Paul, Harvard Medical School; Andrew S. Neish, Harvard Medical School; John D Roback, Emory University; Cassandra D Josephson, Emory University; Duane R. Wesemann, Johns Hopkins University; Daniel Kalman, Harvard Medical School; Seth Rakoff-Nahoum, Harvard Medical School; Richard D. Cummings, Harvard Medical School; Sean R. Stowell, Harvard Medical School
• Language: English
• Date: 2023-06-27
• Publisher: Elsevier
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: © 2023 by The American Society of Hematology.
• Final Published Version (URL): https://doi.org/10.1182%2Fblood.2022018903
• Title of Journal or Parent Work: Blood
• Grant/Funding Information: This work was supported by NIH R01 HL138656, R01 HL 165975 and U01 CA242109 to SRS and by R24GM137763 to RDC. We also appreciate helpful discussions with Akul Mehta, Patricia Zerra and Satheesh Chonat
• Keywords: SARS-CoV-2; receptor binding domain (RBD); galectins; infection; blood binding; blood group A cells
• Research Categories: Biology, Virology

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.