Soon after SARS-CoV-2 began its assault on the world, scientists began searching for clues about what, if any, factors made people more or less likely to get infected with the virus, and more or less likely to get severely sick if they did.
Early studies from China in 2020 suggested people with certain blood types—specifically blood type A—might be at greater risk for getting infected—while those with type O may be protected against infection. Some small studies confirmed the connections, while others did not, leaving public health experts agnostic about how important blood type might be as a potential risk factor for COVID-19.
While working with scientists at the U.S. Centers for Disease Control and Prevention to develop a blood-based test for COVID-19, Dr. Sean Stowell, an associate pathology professor at Brigham and Women’s Hospital and Harvard Medical School, learned the finger-like projections jutting from the SARS-CoV-2 virus were very similar to those from blood groups on human cells. The connection is important because the virus uses those projections, or proteins, as the entryway to bind to and then infect human cells. If the virus recognizes the blood group proteins, then that might mean certain blood groups could enhance the viruses’ ability to infect cells. That would provide an explanation for how blood type might play a role in COVID-19 risk.
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With his team, Stowell did a series of experiments to understand the connection, and reported the results in a paper published this week in the medical journal Blood. He found that, indeed, the cells from people with blood type A were more likely to get infected with SARS-CoV-2 than cells from people with blood type O. Type O is essentially a clean slate when it comes to blood type proteins, so it can serve as a universal donor and be transfused to people with type A, B or AB and not trigger an immune response. Types A, B and AB, however, each contain different groups of proteins, or antigens, which, as Stowell learned, makes them interact differently with the COVID-19 virus.
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In the studies, type A was linked to anywhere from a 25% to 50% increased risk of infection, depending on the particular variant involved. Type A blood group cells were particularly vulnerable to getting infected with Omicron variant viruses.
The reason has to do with SARS-CoV-2’s affinity for type A blood proteins. The virus has receptors that help it to bind to cells with antigens from blood type A, so they’re “stickier” for the virus, says Stowell. With more virus attached to cells, the virus is more likely to find the keyhole it needs to infect cells, called the ACE2 receptor. “Blood group A doesn’t itself help the virus get into cells, but because it makes cells more sticky to the virus, the chance that the virus can find ACE2 receptors and get into cells is higher. Since the group A antigens are all over the place in someone with type A blood, the virus can land on a cell surface more readily than in someone with type O blood,” he says.
Does that mean that people with type A should be especially careful about getting exposed, and are at higher risk of developing more severe disease if they do get infected? Possibly, says Stowell, but it’s not a given. That’s because blood type is one of many factors that influences the risk of COVID-19 infection, as well as the risk of developing severe complications. While some studies have documented that type A is linked to a 48% increased risk of dying from COVID-19, not everyone with type A blood has the same amount of A group antigens among their cells. People also have varying levels of ACE2 receptors on their cells, so even those with type A blood may not necessarily be at higher risk of getting infected compared to people with type O blood. So there could be variability even among those with blood type A.
By the same token, Stowell says people with type O blood shouldn’t assume they have a free pass when it comes to COVID-19. Regardless of blood type, people should continue to take the proper precautions, including staying up to date on their vaccines and wearing masks when infections start rising. “I worry from a public health standpoint that the data suggests that people with type A are more likely to get infected and the counter is that people with type O might be partially protected,” he says. “I don’t want people to think that somehow their blood group status should make them less concerned about being wise and using standard precautionary measures when it comes to COVID-19.”
From a practical standpoint, however, the new information about how blood types may influence COVID-19 risk could help doctors better manage risk among groups such as the elderly and those with compromised immune systems. While those with any blood type will likely be treated the same, if doctors know certain elderly people or cancer patients have type A blood, for example, it might make them more vigilant about watching for signs and symptoms of infection and educating their patients about protecting themselves from exposure.
Stowell plans to build on this work and explore how people with type B blood, whose antigens differ only slightly from those with type A, fare when it comes to COVID-19 risk. “We don’t know why the virus doesn’t bind to type B quite as well, but we are doing that work right now,” he says.
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