Written by Joyce Smith, BS. Researchers found that the SARS-CoV-2 receptor preferentially recognizes the blood group A antigen expressed on respiratory epithelial cells which may explain why individuals with group A blood may be more susceptible to respiratory failure from COVID-19 infections.
The world has witnessed how infection with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), labeled COVID-19 by the World Health Organization, spurred a global pandemic that overwhelmed modern health care systems and played havoc with world economies.
Although SARS-CoV-2 can have devastating outcomes, it appears that susceptibility to infection with the virus can vary greatly. A recent genome-wide association study identified the locus responsible for the ABO(H) blood group expression and found it to be one of the most significant predictors of SARS-CoV-2 infection risk 1. The study’s blood group-specific analysis showed a greater risk of infection for individuals of blood group A than other blood groups and a protective effect for those of blood group O compared to other blood groups. The mechanism by which ABO(H) antigens, and particularly those of blood group A, influence infection remains unknown.
The Stowell research team 2 from Brigham and Women’s Hospital, Harvard Medical School, began researching blood group antigens and the spike protein, called the receptor-binding domain (RBD),on the SARS-CoV-2 virus that specifically recognizes angiotensin-converting enzyme 2 (ACE2) as its receptor to which it attaches and gains entry into cells 3. Spike proteins look similar to galectins which are carbohydrate-binding proteins from an ancient protein family that have been shown to bind to blood group antigens but have no particular affinity for any specific blood group (A, B, or O) 4. The team hypothesize that the SARS-CoV-2 RBD might interact with other host molecules, including blood group antigens, which in turn might increase disease susceptibility. Using a glucan microarray platform populated with many different types of synthetic blood group antigens 5, the team analyzed whether SARS-CoV-2 RBD would recognize and interact with any of the blood group antigens. They found that SARS-CoV-2 RBD had a strong preference for binding only to the blood group A antigen located on respiratory epithelial cells but had no preference for the red blood cells of blood groups A, B or O.
The discovery by the research team that SARSCoV-2 RBD not only shares a sequence similarity with lectins known to bind blood group antigens, but also has the ability to bind to blood group A antigens expressed on respiratory epithelial cells, suggests an association between SARSCoV-2 and blood group A. The mechanism by which SARSCoV-2 RBD preferentially recognizes and attaches to the blood type A antigen (found only in the lungs of blood type A individuals) may provide insight into the potential link between blood group A and COVID-19 infection. While these results do not demonstrate a direct association and given that other mechanisms may also contribute to the clinical COVID-19 picture, researchers stress the need for future studies to elaborate on these initial findings. In addition, they stress that future research should target the potential influence of ABO(H) expression on the adhesion of SARS-CoV-2 to the nasopharyngeal and respiratory tracts and whether the adhesion is ACE-2 dependent or not. Another important research consideration is the potential impact of ABO(H) antigen expression on the thromboembolic complications that frequently occur during COVID-19 disease progression 6.
Source: Wu, Shang-Chuen, Connie M. Arthur, Jianmei Wang, Hans Verkerke, Cassandra D. Josephson, Daniel Kalman, John D. Roback, Richard D. Cummings, and Sean R. Stowell. “The SARS-CoV-2 receptor-binding domain preferentially recognizes blood group A.” Blood advances 5, no. 5 (2021): 1305.
© 2021 by The American Society of Hematology
Posted April 5, 2021.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Ellinghaus D, Degenhardt F, Bujanda L, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. The New England journal of medicine. 2020;383(16):1522-1534.
- Wu SC, Arthur CM, Wang J, et al. The SARS-CoV-2 receptor-binding domain preferentially recognizes blood group A. Blood advances. 2021;5(5):1305-1309.
- Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444-1448.
- Stowell SR, Arthur CM, Dias-Baruffi M, et al. Innate immune lectins kill bacteria expressing blood group antigen. Nat Med. 2010;16(3):295-301.
- Arthur CM, Cummings RD, Stowell SR. Using glycan microarrays to understand immunity. Current opinion in chemical biology. 2014;18:55-61.
- Li J, Wang X, Chen J, Cai Y, Deng A, Yang M. Association between ABO blood groups and risk of SARS-CoV-2 pneumonia. Br J Haematol. 2020;190(1):24-27.
