Your blood type might put you at greater risk for COVID-19, according to a paper published this month in the Blood Advances by researchers from Harvard. Inspired by recent genome-wide association studies which found the locus responsible for blood type expression to be among the most significant genetic predictors of SARS-COV-2 infection, they found that SARS-COV-2, the coronavirus responsible for COVID-19 preferentially binds blood group A, likely making people with this blood type more susceptible to infection.

There are several blood groups found in humans. The basic blood groups are denoted ABO(H) for the carbohydrate chains A, B, AB, and O, with H representing the “Bombay phenotype” which can be present or absent. In addition there is the rhesus factor, which plays a role in blood transfusion compatibility and can be negative (-) or positive (+), making one either A-, A+, B-, B+, and so on.

The reason why your blood type might influence your risk for infection by the virus is because, the receptor-binding domain of SARS-COV-2 shares genomic sequence similarity with an ancient lectin family called galectins that are known to bind blood group antigens.

Galectins are proteins that bind carbohydrates (string of sugars) and exhibit a high affinity (binding capacity) for the blood group antigens.  Genomic sequencing revealed similarities between the receptor binding domain of SARS-COV-2 and human galectin, making the virus capable of recognizing blood group antigens in humans. The receptor binding domain is part of the spike protein on the surface of the virus that is responsible for infection, and researchers have determined that it also displays a preference for blood group A.

Importantly, the virus does not bind well to blood group A antigens expressed on the red blood cells (RBC’s) in the blood, which may be very fortuitous, as this might have lead to hemolysis (red blood cell destruction) or greater morbidity and mortality. However, experiments revealed that the virus instead binds preferentially to organ tissues expressing a variation of the blood group A sugar. Specifically, SARS-COV-2 binds to epithelial cells in the respiratory tract. This can be understood in the adverse respiratory signs and symptoms associated with pulmonary infection by the virus, such as, cough, shortness of breath, pneumonia, and overall damage to the lungs.

The reason for this difference in affinity is that RBC’s express type II (B_1-4) blood group antigens, which differ slightly in structure to the blood group antigens in the respiratory epithelium. Respiratory epithelial cells in the airways of the lungs express type I (B_1-3) blood group antigens. The receptor binding domain of SARS-COV-2 binds the type I structure better than the type II structure found in RBC’s.  Interestingly, this was also reported to be the case with SARS-COV-1, the Coronavirus responsible for the SARS (Severe Acute Respiratory Syndrome) outbreak in the early 2000’s. SAR-COV-1 and SAR-COV-2 share over 85% genomic similarity, so it’s not surprising that the receptor binding domain of their spike proteins would both preferentially bind the same blood type.

Interesting facts about blood groups

• H deficiency is rare; most people have it.
• O+ is the most common blood type and is found most frequently in Black/African-American and Latinx populations.
• Caucasians are just as likely to be blood type O+ as they are A+, the second most common blood type in the United States.  
• AB- followed by B- then AB+ and B+ are the rarest blood types, respectively.

The most significant finding was that SARS-COV-2 recognizes and binds more readily to blood group A antigens, when compared to the other blood groups. Therefore, blood type A is a strong predictor for increased susceptibility to infection by coronavirus SARS-COV-2. As for morbidity and mortality, blood group A has not been associated with increased risk of morbidity or mortality, and the major risks factors for severe disease or death from COVID-19 are age over 65, Caucasian race, and male gender. Though, researchers debate whether blood type A also contributes to the disease severity of COVID-19, it likely plays a role in the progression of the disease.

It is important to note, that while blood type A might increase your risk of contracting SARS-COV-2, there is no blood type that confers protection against the virus and COVID-19. Therefore, it is still necessary to follow all preventative measures such as wearing a mask, social distancing, and hand-washing. Vaccination is also effective at decreasing the risk of severe illness or death from COVID-19 and may also protect against infection in the first place.

References

1. Shang-Chuen Wu, Connie M. Arthur, Jianmei Wang, Hans Verkerke, Cassandra D. Josephson, Daniel Kalman, John D. Roback, Richard D. Cummings, Sean R. Stowell; The SARS-CoV-2 receptor-binding domain preferentially recognizes blood group A. Blood Adv 2021; 5 (5): 1305–1309. doi: https://doi.org/10.1182/bloodadvances.2020003259
2. Ramo A, Mehrotra H, Onwubiko I, et al. Correlation between ABO blood groups and disease severity and mortality in hospitalized COVID-19 patients. Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 104.