The coronavirus SARS-CoV-2 may latch more easily onto the airway cells of people with type A blood compared with those with type B or O blood, a new study suggests. The findings hint at a possible explanation for why, throughout the pandemic, studies have found those with type A blood are likelier to catch COVID-19 and develop severe symptoms than other blood types. Laboratory experiments revealed that part of the coronavirus called the "receptor binding domain" (RBD), which directly binds to cells to jumpstart infection, also grabs onto unique molecules associated with type A blood. These molecules, known as antigens, show up on cells that line the respiratory tract, including the lungs, according to the study, published March 3 in the journal Blood Advances. In theory, binding to these structures may help the coronavirus enter and infect the airway cells more easily — however, we don't know that for sure yet, the study authors told Live Science. "Does this really influence the ability of the virus to get into cells? Does it just influence its ability to adhere to the cells?" said study author Dr. Sean Stowell, a transfusion medicine physician-scientist with appointments at Brigham and Women's Hospital in Massachusetts and Emory University in Georgia. "That's open-ended. We're working on that right now, but the jury is still out." In other words, the data provide the first physical link between the coronavirus and type A blood, but more research is needed to confirm that this difference affects the odds of actual infection. Why would blood type matter? Since the early days of the pandemic, several studies of coronavirus patients have uncovered trends in what blood types seem to become infected most often, Live Science previously reported. "Many studies have found associations between blood groups and propensity for SARS-CoV-2 infections," in particular, showing that people with type O blood have a lower risk of catching COVID-19, compared with non-O blood types, said Dr. Torben Barington, a clinical immunologist at Odense University Hospital and the University of Southern Denmark, who was not involved in the study. People with type A blood may also be more likely to develop severe symptoms and respiratory failure when they do contract the virus, some studies found. "Several hypotheses have been proposed for these associations, but we still need to learn what the mechanisms actually are," Barington told Live Science in an email. This new study hints at a possible explanation for why SARS-CoV-2 may infect blood type A individuals more easily than type O — though it doesn't explain why type B is also linked to more infections than type O, he noted. Stowell said that he and his colleagues were curious about the link between blood type and COVID-19, but that they actually struck inspiration for their new study while developing a diagnostic test for the disease. While creating the test, "we started looking at different parts of the virus and realized that the receptor binding domain … it looks very similar to an ancient group of proteins called galectins," Stowell said. Galectins can be found in all multicellular animals and bind to carbohydrates, or sugar structures, known as glycans; in humans, galectins can be found all over the body and participate in many processes, from muscle development to metabolism to immune cell behavior, Stowell said. In the past, "we've observed that galectins really love to bind to blood group antigens," proteins and molecules that are specific to different blood groups and stick off the surface of cells. Blood group antigens come in two flavors — A and B — and the presence or absence of these antigens determine a person's blood group — A, B, AB, which has both, or O, which has neither, according to the American Red Cross. The antigens are found not only on blood cells in the body, but also on other tissues, including the lining of the lungs. Given the molecular similarity between the coronavirus RBD and galectins, "we thought, 'Well, maybe the virus directly binds to blood group antigens,'" Stowell said. If that were the case, blood group antigens may somehow influence the likelihood of the infection taking hold, he said. For example, some viruses accrue on cells by first grabbing hold of glycans on their surfaces, according to a 2016 report in the journal Current Opinion in Structural Biology; the viruses then let go of these glycans to slip through nearby entryways into the cell, triggering infection. Something similar could potentially be happening with blood group antigens and SARS-CoV-2, the authors thought. With this hypothesis in hand, the team headed to the lab to run experiments. In the lab The team analyzed how the RBD interacted with red blood cells isolated from blood group A, B and O individuals; they also ran experiments with synthetic blood group antigens, based on antigens found on both respiratory and red blood cells from the three blood groups. This allowed the team to compare whether and how the RBD binds with blood group antigens on blood cells and in the respiratory tracts. "The flavor of blood group antigens that are expressed on the surface of red blood cells are slightly different than the flavor that lines our lungs," Stowell noted. Specifically, due to their differing molecular structures, the antigens bind a little differently to respiratory cells than they do to blood cells, he said. What's interesting is that this subtle difference seems to matter to the RBD of the coronavirus, he said. Based on the experiments, the RBD doesn't readily bind to any of the red blood cell antigens and shows no preference between the blood types, in this regard. In contrast, the RBD "exhibited high preference" for the type A antigens found on respiratory cells. "It was clear; there was this preference. We didn't expect that," Stowell said. Now, "whether that actually means that the virus is more likely to infect blood group A, I'd say, we don't know." Given that these data were drawn from lab experiments, the result may not perfectly reflect what happens in the human body, said Fumiichiro Yamamoto, an immunohematologist at the Josep Carreras Leukaemia Research Institute in Barcelona, who was not involved in the study. "The binding may or may not reflect the actual situation on the cell surface," especially since the density of antigens on the cell surface may differ from scenarios tested in the lab experiments, Yamamoto told Live Science in an email. Additionally, in the body, other substances compete to bind to the same blood group antigens, so it's unclear how many coronavirus particles would ultimately latch on, he added. What's more, the type A antigens found on the surface of airway cells can also be secreted elsewhere in the body, such as in the saliva, he said. That means the virus could potentially bind to these free-floating antigens, as well, decreasing the number of viral particles that reach the respiratory cells, he said. And in addition to unique antigens, different blood types also carry specific blood group antibodies, molecules that help the immune system eliminate foreign invaders, Barington said. These antibodies are particularly "prevalent in blood group O individuals and have been proposed to neutralize virus on our mucosal surfaces," he said. It may be that both blood group antigens and antibodies influence the likelihood of COVID-19 infection, and their individual contributions will need to be sorted out, he said. In regards to the new study, "it's an important first step," Stowell said. "The critical thing to do [now] is to determine whether the actual virus, in terms of its ability to infect cells, is influenced by blood group antigens or not." Source
