Blood type and coronavirus susceptibility

Researchers recently posted a preprint publication showing that blood type seems to be related to susceptibility to the coronavirus. While this may seem odd at first, there are actually quite a few viral and bacterial pathogens – as well as chronic diseases – that are influenced by blood type.

This article explains how your blood type can influence cardiovascular disease and diabetes and how your immune response is linked to your blood type. We will wrap up with an explanation of the preprint article on COVID-19 and blood type, along with research from the original SARS outbreak that may shed some light on this link.

Blood groups and pathogen susceptibility

Let me start off with a quick explanation of blood groups (skip ahead if you know all of this). There are actually many different blood groups, but for this explanation, I’m going to focus only on ABO typing.

ABO blood types:

There are four ABO blood types: A, B, AB, or O.

All cells have a type of glycoproteins called an antigen on the plasma membranes. Your immune system recognizes these antigens as marking the cells as being ‘self’. In contrast, antigens on the surface of invading pathogenic bacteria or viruses are recognized as being foreign and then attacked by your immune system.

On red blood cells (RBCs) there is a specific type of antigen called and agglutinogen. A type has A antigens, B type has B antigens, AB has both, and O has no antigens.

People with type A blood produce the A antigen and have antibodies that react against type B blood. People with type B blood produce the B antigen and have antibodies that react against type A blood.  Type AB, the rarest blood type, has both antigens produced and creates no antibodies. Type O blood produces no antigens but has antibodies against both A and B.

While we refer to this as your ABO blood type, these antigens are also found on platelets, leukocytes, plasma proteins, certain tissues, and some cell surface enzymes. Also, the antigens exist in a soluble form, not connected to the cell surface, and this can be secreted (by the majority of people) in the sweat, saliva, breast milk, urine, and gastric secretions. [ref]

While pictures of red blood cells may show these antigens as a few little spikes, each red blood cell can be decorated with about 2 million of the antigens for the ABO blood type. [ref]

A quick history time-out:

Blood types were first identified in the early 1900s. It had been observed that mixing some individual’s blood with others would cause agglutination – clumping together of red blood cells.  By the mid-1940s, a test had been developed to determine which types of antibodies were in the blood, thus paving the way for blood transfusions.

It is hard to imagine in this day and age of genetic testing, machine learning, and world-wide connectivity that blood typing is such a relatively recent concept.

Digging into the specifics:

These antigens are made up of glycoproteins – a sugar molecule chain called an oligosaccharide with a protein. The oligosaccharides differ in the sugar molecule at the end of the chain, and this is what determines the A antigen and B antigen (with the lack of either being type O).

The A and B antigens come in two types (Type I and II).  Type I antigens are the main type that is secreted by about 80% of the population in their saliva, mucus, semen, etc. The Type II antigens are present on red blood cells (e.g. different ones for type A vs type B) and also on epithelial cells and endothelial cells.[ref]

Getting a little bit deeper there, there are actually two types of blood type A antigens – A1 and A2. “A1 red cells express about 5 times more A antigen than A2 red cells…” [ref]

Infants are usually born without anti-A or anti-B antibodies. They develop the antibodies as they are exposed to bacteria and their immune system develops. [ref]

Variations by population group:

The percentage of a population who carries each blood type varies considerably from one play to another.

Keep in mind that people with type A blood can carry either two A alleles or an A and an O allele. Similarly, type B can carry either two B alleles or a BO combination. People with type O blood carry two O alleles.

Here is a map of the distribution of type A allele among native populations:

Here is a map of type B alleles among native populations:

Finally, a map of type O alleles by native population:

 

Want to dive deeper into this? Here is a breakdown by current country populations and by ethnic group.


Chronic conditions in which blood type matters:

There are quite a few diseases for which risk differs based on blood type. Part of this may be due to the blood type being presented on the endothelial cells, which are the cells that line blood vessels, rather than the presence of the antibodies on the red blood cells. It also may involve the flow of blood and coagulation factors in the plasma.

Cardiovascular events:

  • A study of 30,000 individuals followed for 6 years in the US found that type AB was at an 83% increased risk of stroke (compared to type O) and another study found that type B was at a 59% increased relative risk of stroke.[ref][ref]
  • In comparison to type O, people with type A, B, and AB are at an increased risk of blood clots (ranged from 79% to 170% increased relative risk). [ref]
  • Another study found non-O blood types to be at a 2-fold risk of thrombosis. [ref]
  • A two-year-long study of 3800+ patients in China found that the non-O blood types were at a 32% increased risk of cardiovascular events. [ref]
  • Atherosclerosis risk is linked to blood type also. People with type A were more likely to have higher severity scores, and people with type O were less likely to have a higher severity score. [ref]

Diabetes risk by blood type:

  • A study of over 84,000 people who were followed for 18 years found that people with blood type A were at a 10% increased risk of diabetes and people with blood type B were at a 21% increased risk for diabetes when compared to blood type O. Type AB seems to fall in the middle of the risk between A and B, and Rh-positive vs negative didn’t make a difference. [ref]

Non-alcoholic fatty liver disease:

  • A study of over 2,000 people found that, compared with people who were type O, people with type A were at a 50% increased risk, type B was at a 59% increase risk, and AB was at a 37% increased risk of non-alcoholic fatty liver disease.

Cognitive Impairment and Psychiatric disorders:

  • People with AB blood type were at an 82% increased relative risk of cognitive impairment. [ref]
  • A Croatian study found that people with the AB blood type were at a three-fold increased risk of psychiatric disorders.[ref]

Blood type and Immune System function:

There are a number of studies showing that blood type is important in the immune system and matters in the risk of various pathogenic diseases.

Malaria:

  • One study found that people with blood type O are at a 66% reduced risk of getting malaria compared with type A, B, and AB.[ref]
  • Other studies, though, indicate that it may just be a reduction in the risk of severe malaria instead. [ref]

Sepsis:

  • In patients critically ill with sepsis or trauma, blood type A increases the risk of acute kidney illness.[ref]
  • In infants, blood type AB is associated with an increased risk of sepsis, respiratory distress, and negative outcomes.[ref]

Acute Respiratory Distress Syndrome (ARDS):

  • In a Caucasian population, blood type A was associated with an increased risk of ARDS. This didn’t hold true, though, for an African American population. [ref]

Cholera-  ‘O’ no:

  • While it may seem that type O is best for most disease risks, for cholera, type O has been shown in several large studies to be a major disadvantage. In fact, researchers think that the low prevalence of type O blood in regions like Bangladesh that are prone to cholera outbreaks is due to the higher susceptibility to severe outcomes for type O people. [ref]
  • Older studies show that people with type A are least likely to be affected with cholera, while type O individuals may be at a 2-fold increased risk of the disease, especially severe disease.[ref]

Why is blood type important for chronic diseases and immune function?

Recent research explains that the ABO type on platelets regulates how they interact with von Willebrand factor, which is a glycoprotein found in the plasma. Von Willebrand factor is important for binding to other proteins and is important for blood clotting. It is also important in how blood flows through narrow vessels — affecting different sheer forces and flow rate. Researchers think the reason that people with type O blood are a little less likely to have vascular disease is likely due to the way that platelets (which also express ABO antigens) are less likely to bind with the von Willebrand factor. [ref]

For some pathogens, the presence or absence of the actual ABO antigen may play a role in how well they can survive. Cholera is one example. Another example is that people who don’t secrete their blood type are likely to be immune to most strains of the norovirus and rhinovirus. (article- check your type.) [ref]


COVID-19 and Blood Type:

A recent preprint study found that blood type was significantly linked to susceptibility to SARS-CoV2 infections. [ref] This has made headlines as a susceptibility factor for the coronavirus.

First, some caveats: This is a pre-print of a study, which means that it hasn’t undergone a peer review process that looks for flaws in the methods or statistics. Second, the data was only looking at people with severe cases of the disease in a hospital in China, so the data may be more indicative of susceptibility to severe COVID19 rather than overall susceptibility.

The researchers found that people with blood type A had a 20% higher risk for COVID19, while people with type O blood had a 33% decreased risk for the disease.

While these results obviously need to be replicated in other population groups, the decreased susceptibility for people with type O blood is in line with many other pathogen studies as well as studies on Acute Respiratory Distress Syndrome (ARDS).

Why the increased susceptibility only for people with Type A?

Research on the SARS virus outbreak in 2003-2003 may shed some light on why people with type A blood may be more susceptible.

A study from 2008 investigated why people with blood type O were at “very low odd of infection” from the original SARS virus. The original SARS virus also had a spike protein that binds to the ACE2 receptor, which is the receptor on lung and digestive cells that allows the virus to come inside the cell to replicate. (This is the way the current SARS-CoV2 virus replicates, as well.) Once the host cell has replicated the virus, the spike protein of the virion may contain the host blood type antigens.

The 2008 study showed that for the original coronavirus, the binding between the spike protein and ACE2 receptor could be blocked by the host’s anti-A antibodies.[ref] People with blood types B and O both produce anti-A antibodies.

Another possibility here is that the same link with increased risk of ARDS, sepsis, and cardiovascular problems for people who are non-Type O could be driving the differences in susceptibility to severe COVID-19.

Do people with Type O blood not need to worry about COVID-19?

While there may be a statistical difference in the percentage of the population with type O blood and hospitalization for COVID-19, people with type O blood can definitely get the virus and may die from it. 

Blood type is just one factor, among many, that statistically may affect susceptibility at a population level. It is one of those things that geeks and researchers find interesting.  But as an individual, you should still wash your hands, stay away from people who are contagious, and avoid getting this virus.

 


Related Genes and Topics:

Acute Respiratory Distress Syndrome (ARDS) genes
ARDS is caused by an overwhelming immune response to a virus, bacteria, or lung injury. Learn more about which of your immune system genes are involved in ARDS.

Viral Immunity: Your genes protect you
Your genetic variants shape your immune system and give you superpowers against some pathogens – and perhaps more susceptible to others.

Non-secretors: Norovirus resistance and gut microbiome
A genetic variant in the FUT2 gene controls whether or not you secrete your blood type into your saliva and other bodily fluids, such as your intestinal mucosa. This alters the gut microbiome – and protects you from Norovirus.

Hemochromatosis – Too Much Iron
A couple of common mutations can cause you to build up iron, leading to iron overload or hemochromatosis. This is one genetic disease where knowledge is really powerful – you can completely prevent hemochromatosis through blood donations.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.