In This Article
- There has been a lot of recent press around early studies that found potential correlations between a person's blood type, their risk for COVID-19 infection and disease severity
- A Massachusetts General Hospital study published in the British Journal of Haematology found that among critically ill COVID-19 patients, there was no association between blood type and mortality rate among any race or ethnicity
- Researchers found that type A blood was seen more commonly and type O blood less commonly than would be expected in white patients; they did not observe this in Black or Hispanic patients
- In this Q&A, Rebecca Karp Leaf, MD, and Hanny Al-Samkari, MD, give us a rundown of what is known to date about the correlation between blood type and COVID-19 transmission/severity, findings from their study and why this connection may or may not exist
There has been a lot of recent press around early studies that found potential correlations between a person's blood type, their risk for COVID-19 infection and disease severity. A Massachusetts General Hospital study published in the British Journal of Haematology found that among critically ill COVID-19 patients, there was no association between blood type and mortality rate among any race or ethnicity. They also found that type A blood was seen more commonly and type O blood less commonly than would be expected in white patients, but they did not observe this in Black or Hispanic patients.
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In this Q&A, the study's lead authors, Rebecca Karp Leaf, MD, a non-malignant hematologist, and Hanny Al-Samkari, MD, a classical hematologist and clinical investigator, both at the Center for Hematology at the Mass General Cancer Center, give us a rundown of what is known to date about the correlation between blood type and COVID-19 transmission/severity, the findings from their study and why this connection may or may not exist.
Q. How does blood type affect a person's response to an infectious disease?
Dr. Karp Leaf: I wouldn't say that for every disease blood type is important—it's definitely not—but there are some infectious diseases where it does make a difference in terms of your chance of acquiring that disease or how severely the disease manifests.
The prime example of this is Plasmodium falciparum (a type of parasite that causes malaria). Individuals with type O blood who contract malaria often have less severe disease, and we see genetic pressure for type O blood in regions where malaria is endemic.
Dr. Al-Samkari: I would also add that in our area of hematology, the most common bleeding disorder in the world is von Willebrand disease: a genetic bleeding disorder caused by a missing or defective blood-clotting protein. Something as simple as a patient's ABO blood group impacts the level of von Willebrand protein that is in their blood. So, blood type does have an impact beyond making sure you get the right kind of blood when you get a transfusion. It's a topic of interest among people in our field and among blood bankers to understand how it could impact the likelihood of getting certain diseases.
Q. What was known about COVID-19 and blood type before your study began? What piqued your interest in studying blood type and COVID-19?
Dr. Karp Leaf: With SARS-CoV-1 in 2003 in Hong Kong, there was a small study that showed that health care workers with type O blood were less likely to get the disease than health care workers with other blood types.
When SARS-CoV-2 came around, clinicians started looking for a good explanation for why some people were more susceptible to the virus and others were seemingly protected. They looked to this older data and started wondering if these differences were related to blood type.
Dr. Al-Samkari: There are also some other reasons why there has been a lot of press about COVID-19, clotting issues and blood types. People are really interested in blood types. People often know their blood type, and rightly or not, it's something they think about when it comes to disease risk.
Q. Can you tell us more about your recent COVID-19 ABO study?
Dr. Al-Samkari: Our study was a sub study of the STOP COVID trial, which is a very large nationwide U.S. study of treatment outcomes in patients with COVID-19 who are critically ill. There were 67 institutions that contributed patient data to the trial, which resulted in a rigorous collection of data from the first several weeks of the pandemic as it was exploding.
Based on studies that suggested that patients with type A blood were more susceptible to getting COVID-19, we decided to do our own study to see if there was any truth to these prior data. We did an analysis of about 2,000 patients in the study who had blood type information available. We looked to see if certain patients with certain blood types were overrepresented compared to what would be expected in this cohort, who were geographically distributed throughout the U.S. and included multiple races and ethnicities. Then we asked, "Are more patients with a certain blood type dying than would be expected?"
And in a nutshell, what we found was that there were more white or Caucasian COVID-19 patients with type A blood than we would have expected and fewer with type O blood than we would have expected when compared to a study of healthy blood bank donors of three million people. This was not true for COVID-19 patients who are Black or African American or for patients who are Hispanic versus not Hispanic.
But most importantly, there was no significant difference in the mortality observed versus the expected mortality for each blood type when split out by race and ethnicity.
Dr. Karp Leaf: The bottom line is there was no difference in mortality. And we also have to think: Are healthy blood donors the best comparator group to use? The reason is that blood donors are enriched for type O blood (the "universal donor") and blood banks are more likely to need them to donate, so perhaps it looks like there are more people with type O in the general population.
There was a recent study in the New England Journal of Medicine that found two gene clusters enriched in patients with COVID-19; one of these clusters is responsible for control of a person's ABO blood group. That population was also enriched for patients with type A blood when compared to blood donors and patients without COVID-19. However, there did not seem to be an association between blood groups and the need for mechanical ventilation in this study.
Q. Why might blood type A lead to more infections/worse outcomes? Why might blood type O confer protection?
Dr. Karp Leaf: Some people have hypothesized that since patients with type O blood have lower levels of von Willebrand factor, they may be less likely to clot. And we do have data that patients with COVID-19 have a high risk of thrombosis. So, if you have type O and you have lower levels of von Willebrand, you might have a less dramatic clotting response than somebody with another blood type. But that doesn't explain why somebody would be more or less susceptible to getting the disease in the first place, only why they may or may not get more severe disease. Again, this is just a hypothesis.
There's also a hypothesis that anti-A antibodies stop the virus from entering host cells via the ACE2 receptor. Patients with type O blood have anti-A antibodies. But if you follow this logic, then people with type B blood would also be protected. And again, a lot of this work is based on small in vitro studies.
The point is, we really don't know.
Dr. Al-Samkari: In the discussion in our paper, we did write that if this was a true signal that was attributable to, let's say, the presence of anti-A antibodies in patients with type O blood, you would expect to see that in Black and Hispanic people as well, not just white patients. I think that we can't necessarily explain exactly why we found what we found here, but I think we feel relatively confident that our findings are not representative of some protective aspect of type O or some detrimental aspect of being type A.
Dr. Karp Leaf: We also have to point out that there is no biological reason why type A blood predicts severe disease in white patients and not in patients who identify as Black or Hispanic. It's also important to note that reporting of race in the U.S.—both in the blood donor population and in medical records—is highly variable and fraught with bias. So, we do have to be wary of that.
Q. Is there anything else you would like to say on this topic?
Dr. Al-Samkari: Just my two cents regarding studies in general: In the end, when there's multiple studies, each with a minor effect or no effect, and there's no clear effect pointing in one direction, that usually means that there's nothing there, or if there is something, it's minor.
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