COVID-19 and blood group
Since the start of the global pandemic, scientists have been working to determine what particular factors increase a person's likelihood of becoming infected with SARS-CoV-2, and what factors contribute to the clinical variability observed in COVID-19 patients.
One area of focus has been the potential influence of blood group. "There are a few clinical correlative studies that suggest blood group A individuals may be more likely to not only get infected with the virus, but may also experience a more severe disease course," says Dr Sean Stowell, associate professor of pathology at Brigham and Women's Hospital. Stowell is the lead researcher of a new study published in Blood Advances that adds to this body of work.1
SARS-CoV-2 entry into human cells is mediated by a protein on the viral surface known as the spike protein. This protein binds to the human receptor angiotensin-converting enzyme 2 (ACE2) via the virus's receptor binding domain (RBD).
The RBD is the focus of Stowell and colleagues’ latest research, he explains: "The blood group A antigen is a carbohydrate structure, and the RBD of SARS-CoV-2 possesses sequence similarity to an ancient family of carbohydrate binding proteins – called galectins – which we have previously demonstrated bind to blood group antigens. We sought to determine whether the receptor responsible for SARS-CoV-2 viral entry may directly engage the blood group A antigen."
What are blood group antigens?
Blood group antigens are either sugars or proteins that are attached to different components of the red blood cell membrane. The types of blood group antigens that present on your red blood cells determine your blood group. For example, blood group ABO antigens are sugars, whereas the blood group Rh antigens are proteins.
Their role is largely unknown, and science has not found any detrimental effects caused by their absence. However, they are incredibly important to consider in the context of blood transfusions, because any antigens that are not "self-antigens" – i.e., from a donor – can trigger unwanted immune responses. That's why donor blood must be cross-matched before it is administered to a recipient.
The scientists used a microarray that was populated with distinct types of blood group antigens to determine whether the RBD of SARS-CoV-2 may prefer blood group A. "This would provide a possible explanation for clinical observations of an association between blood group status and infectious risk," Stowell says.
SARS-CoV-2 RBD binds preferentially to blood group A antigens
The scientists discovered that the RBD of SARS-CoV-2 showed preference for binding to blood group A antigens on respiratory cells, not red blood cells. This finding was only applicable to blood group A. The RBD did not show preference for binding to any other blood group antigens found on respiratory or red blood cells.
When asked about the potential impact of this data in understanding COVID-19 susceptibility, Stowell said, "It is possible that the ability of the RBD to bind to the blood group A specifically found on respiratory epithelial cells may facilitate viral adherence following initial exposure or actual cellular infection. However, additional studies are certainly needed to define the possible influence of blood group A on actual SARS-CoV-2 infection."
Stowell and colleagues also explored whether the RBD of SARS-CoV, a related coronavirus that caused the severe acute respiratory syndrome outbreak in 2003, demonstrated any interesting interactions with blood group antigens. "We found the same phenomenon. The RBD of SARS-CoV preferentially bound to the blood group A uniquely expressed on respiratory epithelial cells. This was particularly interesting, as prior reports had likewise observed an association between blood group A and SARS-CoV infection," says Stowell.
Of course, we cannot change our blood type – it is inherited. So how might these study results be utilized? Stowell says that, if interactions with blood group antigens indeed influence risk of infection, therapeutic or prevention approaches that leverage the blood group antigen (or similar structures) could be used to reduce – or prevent – SARS-CoV-2 infection.
It's important to note that the study simply examined binding of the critical domain, the RBD, to synthesized carbohydrate blood group antigens presented in a microarray format. "While this approach provides a more definitive way to examine the fine specificity of the RBD toward distinct blood group types, studies actually examining SARS-CoV-2 infection of respiratory cells isolated from blood group A, B or O individuals are needed to truly define the influence of these antigens on infectious risk," says Stowell.
The next steps for the research team are to extend their work to look at cells that express various types of blood group antigens. "These studies are currently underway, and we hope will provide more insight into how blood group A antigen engagement may influence SARS-CoV-2 infection," Stowell concludes.
Sean Stowell was speaking to Molly Campbell, Science Writer for Technology Networks.
1. Wu SC, Arthur C, Wang J, et al. SARS-CoV-2 receptor binding domain preferentially recognizes blood group a. blood advances. 2021. https://doi.org/10.1182/bloodadvances.2020003259.