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Infectious disease

Genetic study suggests that people’s blood type may affect their COVID-19 risk

People with type A blood may have higher risk of severe illness, while those with type O may have lower risk

by Alla Katsnelson, special to C&EN
June 11, 2020 | APPEARED IN VOLUME 98, ISSUE 23

 

09823-scicon3-typeo.jpg
Credit: Shutterstock
People with type O blood may have a lower risk of developing severe respiratory illness from SARS-CoV-2.

Last week, a genetic study of more than 1,610 COVID-19 patients in Italy and Spain found that people with type A blood had a higher chance of developing severe respiratory failure than people with type O blood (medRxiv 2020, DOI: 10.1101/2020.05.31.20114991). The findings add support to an idea that has been developing since early in the global pandemic, that type O blood is somehow protective against the disease, while type A may make people more vulnerable.

In the new study, researchers sequenced the genomes of COVID-19 patients in Spain and Italy who had been hospitalized with severe respiratory failure and compared variations in their DNA sequences to those of 2,205 healthy subjects. They found two regions of DNA in which sequence variations were significantly tied to how severely ill the people got. One of those regions contains the gene coding for a person’s ABO blood type. The findings were published on the preprint server medRxiv and have not yet been peer-reviewed.

On June 8, the personal genomics company 23andMe released preliminary results from a study of 750,000 people that came to similar conclusions. The company found that people with blood type O were 9-18% less likely to get COVID-19 than people with other blood types. The results from both of these recent studies align with those from a handful of other reports published earlier this year, including two preprints from a Wuhan (medRxiv 2020, DOI: 10.1101/2020.03.11.20031096) and a New York hospital (medRxiv 2020, DOI: 10.1101/2020.04.08.20058073), and a peer-reviewed study from Wuhan (Br. J. Hematol. 2020, DOI: 10.1111/bjh.16797).

It’s hard to say much about the 23andMe results because the company did not publish its data, says Fumiichiro Yamamoto, an immunohematologist at the Josep Carreras Leukaemia Research Institute in Barcelona, who identified the gene that encodes the blood type antigens in the 1990s. But, he says, the evidence of a link between risk of severe COVID-19 disease and blood type is now solid. The recent medRxiv study “is much more conclusive,” than previous work because the researchers searched through 8.5 million gene regions in an unbiased manner to come up with the association, Yamamoto says.

It’s not yet known how exactly blood type might play a role in SARS-CoV-2 infection. Andre Franke, a molecular geneticist at Kiel University and the co-lead author of the medRxiv study, told the New York Times on June 3 that he could only speculate on this question. He also noted that the gene region that codes for blood type is also associated with elevated levels of a key immune molecule, so theoretically, that too could contribute to the COVID-19 link. However, researchers who study blood type have some concrete ideas, based in part on research conducted during the 2002-3 severe acute respiratory syndrome (SARS) epidemic, caused by SARS-CoV-1, a viral cousin of the COVID-19 coronavirus.

Blood type is determined by specific sugar molecules that are added to proteins or lipids on our blood cells and other cell types. People with type A blood carry so-called A sugar antigens, those in people with type B blood have B antigens, and people with type O blood have neither. Correspondingly, the immune systems of people with type A blood develop antibodies for B antigens, people with type B blood have antibodies for A antigens, and people with type O blood have antibodies for both.

The spike protein of SARS-CoV-2, which is a key molecule the virus uses to infect cells, is also heavily glycosylated, says Laura Cooling, director of immunohematology at the University of Michigan. “The spike protein has got tons of sugars on it, and the virus is borrowing the host enzymes to put those sugars together,” she says. Research on SARS-CoV-1 suggested that the spike protein of virus particles often carry the blood group sugar antigen of the infected host cell that produces the pathogen.

SARS-CoV-2 can replicate in cells that express blood type antigens, says Jacques Le Pendu, a glycobiologist at the University of Nantes. So when an infected person coughs or sneezes, they possibly release viral particles coated in their blood type antigens. That means if a person with type A blood transmits the virus to a person with type O blood, the type O person will have antibodies that can fight the virus. However, if the person inhaling the particles is also type A, they won’t have those antibodies.

Data from the SARS epidemic also seems to support the type O protection idea. A 2005 report analyzed the fallout from one infected patient exposing 45 healthcare workers in a Hong Kong hospital to the SARS-CoV-1 virus. Of the 19 people with type O blood, 8 became infected, but of the 26 people with other blood types, 23 became infected (J. Am. Med. Assoc. 2005, 10.1001/jama.293.12.1450-c). In subsequent lab studies, Le Pendu found that antibodies against type A antigens block the interaction between SARS-CoV-1’s spike protein and the host cell receptor it uses to get into cells, but only if the virus particles had been made in cells that could express the A antigen.

But Cooling notes that the idea that having type O blood is protective doesn’t match up with the COVID-19’s epidemiology in the US. Type O blood is more prevalent among African Americans, yet African Americans have experienced disproportionately high infection rates. That epidemiological data suggests that the blood type protective effect might be quite small, compared with other factors, she says. “It’s what your blood type is, relative to the other person who exposed you, relative to all the other genetic and acquired health conditions you have,” she says.

Although the medRxiv study did not find an association with blood type B, both Yamamoto and Le Pendu suspect that a study including more type B people might find that the blood type shows the same increased risk as type A.

The presence or absence of blood type antibodies is not the only way that blood type might affects the body’s response to infection with SARS-CoV-2. Blood type influences blood clotting and a growing body of evidence suggests that COVID-19 pathology often involves overactive blood clotting. People with type O blood have lower levels of proteins that promote blood clotting. “This also strengthens the argument that group O individuals are least likely to be severely damaged by this disease,” Yamamoto says.

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Comments
Christina Hammer (June 12, 2020 2:09 PM)
I am concerned 56 female with factor five Lieden and AB positive blood type. Can I be taking something to reduce my chances of a bad outcome from covid? Thank you
Elizabeth (June 14, 2020 8:45 PM)
Christina,
My adult daughter is heterozygous, factor 5 Lieden ( and also AB positive). We keep her INR between 2.5 and 3. She will always make clots, but her blood is kept quite thin- so the rest of her blood will flow around her clots. I would think this would be the same if she were to be infected by Covid-19. She checks her INR monthly, more frequently if she isn’t in range.
Hope this gives you a bit of support.
Michelle Frank (June 17, 2020 3:13 AM)
Yes make sure you are not deficient in vitamin D. Excessive vitamin D can do damage. Search the YouTube videos for dr. John Campbell he is extremely educational. as of today he even posted with doctorate willinger about Sweden and their governmental policy. Sweden government is promoting palliative care for the elderly. When often supplemental oxygen via mask, antibiotics to support any secondary infections, and IV fluids could resolve some of the elderly cases.
It is a sad case in Sweden. But make sure you are not deficient for vitamin D.
Dr.Hu (June 17, 2020 3:23 PM)
If you take 500mg off a good Vitamin B-1 Thiamine Hydrochloride at dawn each day,
no air borne SARS or COVID viruses will be able to live in your body that day,since,
that feeds all your white blood cells,what they need to reproduce and destroy them.
But since our body does not store excess sulfides,you have to be sure take B1 every day.
Xander (June 27, 2020 9:19 PM)
Can you cite your source?
steven j turner (June 30, 2020 12:29 PM)
Please stop spreading dangerous misinformation with zero scientific evidence.
Joe Nosotti (June 13, 2020 5:26 PM)
Interesting findings. Where would blood type AB fit?
Alla Katsnelson (June 19, 2020 5:30 PM)
Hi - Thanks for your question! I should have explicitly noted this in the story - the GWAS study did not look at people with AB blood, perhaps because it is rare. But based on the reasoning described in the story, people with AB-type blood would be at least as susceptible as people with A-type blood. That's because people with AB-type blood lack both A and B antibodies.
Zetty (June 13, 2020 5:29 PM)
There's 4 blood types not just 3 -- how about AB?
Jenn (June 19, 2020 9:08 AM)
Found info about AB in this article https://www.google.com/amp/s/www.livescience.com/amp/why-covid-19-coronavirus-deadly-for-some-people.html
Thomas L Perkins (June 13, 2020 5:42 PM)
OK but what about A negative blood type blood?
Fred (June 14, 2020 2:08 PM)
The 'negative' part of 'A negative' is about an extra factor, called the rhesus antigen. A negative people have blood type A, without the rhesus antigen, so would be (hypothetically) at the same risk as those with A positive blood (ie. Blood type A, with the rhesus antigen).
Carisa Stephens (June 13, 2020 7:19 PM)
Are there any results for blood type AB? Does type AB carry antibodies for both types A and B or neither? I'm surprised this article (& the base case?) had no data / results for this category in the ABO blood categories. How do people with type AB fare in the fight against Covid-19?
Fred (June 14, 2020 2:11 PM)
People with type AB blood have both the A and B antigens, and so won't have antibodies to either antigen. Hypothetically, they wouldn't be protected by their blood type.
Alla Katsnelson (June 19, 2020 5:31 PM)
Indeed - they didn't look at that directly, but that is what I would surmise.
Proscovia (June 14, 2020 1:09 AM)
The results from the several studies are consistent, however, underlying factors could also be considered.
CORREEN SPECE (June 14, 2020 7:52 PM)
What about the RH factor? I'm RH negative, A negative to be exact.
Alla Katsnelson (June 19, 2020 5:32 PM)
The GWAS study did not look at RH factor, unfortunately.
Jimmy Hawkins jr (June 14, 2020 2:48 PM)
What about AB- BLOOD TYPE? I know it's very rare but a few of us are AB-!!!
Alla Katsnelson (June 19, 2020 5:34 PM)
The large genetic study did not look at AB blood type directly, but if the protection comes from antibodies, as blood type experts guess, then people with AB type blood would be at least as susceptible as people with A type blood.
J. O'Hanlon (June 15, 2020 9:20 AM)
Oh! Dear, we are an A Negative family . Myself, wife, daughter, son-in-law and two grandchildren all A Negative..
So we live with the heightened risk? So stay isolated ??!. Joe
Michelle (June 15, 2020 10:33 AM)
Has there been any research on sickle cell blood trait/ disease and covid 19? Would this explain higher mortality in African Americans and Mediterranean populations?
Katheryn (June 15, 2020 7:45 PM)
What about people with thalassemia anemia?
Samir Maher (June 16, 2020 6:00 AM)
What about type AB. That is AB+ and AB-
Don (June 17, 2020 8:34 AM)
What about anti-A,B (not anti-A or anti-B) found only in group O people which could be protective and explain why group B are not protected? The carbohydrate (sugar) structure recognized by anti-A,B are unknown but could be present on the Spike protein? Perhaps African-Americans have lower levels of anti-A,B than do other ethnicities and therefore are more susceptible to SARS-CoV-2 infection?
Alla Katsnelson (June 21, 2020 10:43 PM)
Hi Don - the genetic study did not look at people with AB blood, perhaps because it is rare. But based on the reasoning described in the story, people with AB-type blood would be at least as susceptible as people with A-type blood. That's because people with AB-type blood lack both A and B antibodies.
Philly (June 28, 2020 11:14 PM)
It's probably not genetics - the higher incidence of COVID deaths in African Americans is explained effectively by the higher rate of prior health conditions and higher risk of exposure among African Americans in the US, which relates to their higher rate of poverty and working jobs that don't allow for telecommuting. The fact that the disparity between White and Black deaths seems to be highest in areas where inequality is especially high further supports this thinking. Indigenous communities in the US are also experiencing high rates of death, similarly explained by their disproportionate economic and societal disadvantages.
In short, COVID didn't level the playing field here. It further exposed the huge inequalities present in our system.
Rena Leibovitch (June 17, 2020 2:39 PM)
What would be the effect of taking blood thinning drugs? I am an older person with type B blood and conditions that require blood thinner to reduce incidence of stroke. Could this help to protect me against COVID infection or reduce the severity if acquired?
Don (June 22, 2020 8:17 AM)
Sorry Alla, anti-A,B is not meaning AB blood. It is an antibody, IgG, that is only found in blood group O people. It is NOT anti-A or anti-B but an antibody that reacts with a carbohydrate (sugar) antigen, as yet to be elucidated, that is neither A or B but BOTH that is found on blood group A and blood group B and AB people (not found on blood group O). It is possible that any resistance by blood group O people to SARS-CoV-2 infection is related to only this blood group having anti-A,B and that the glycoprotein of the spike protein has this antigen or an antigen that is crossreactive with the anti-A,B and that would explain the blood group associations reported.
Carole Madore´ (June 22, 2020 11:48 AM)
Has there been any study of covid19 on the differences in RH+ or RH - factors in blood types?
Don (June 24, 2020 8:11 AM)
The genetics study listed on this page would have checked on the Rh type and would have shown an association with COVID-19 respiratory effects if there was one. One problem with Rh type is that most people are Rh+ so it is possible that not enough Rh- patients have been evaluated but I would think that Rh would not be involved as this antigen is ONLY found on red blood cells; whereas ABO antigens are found on most cells in the body (known as histo-blood group antigens), including lung cells and platelets.
Melissa (June 24, 2020 6:30 AM)
Good question Don. Anti A,B is a different monster than anti A or anti B. I have also wondered about the Rhesus factor. Looking at the percentages that appear immune would the combo of being both group O and type RH- could be a factor. African Americans have other antigens or lack of on their blood cells that help protect them from some disease such as malaria. Maybe some of these differences is what makes African Americans more susceptible?? But immunity to some diseases due to blood antigens has been around forever.aimmunity attributed to groups has been around forever. I think it deserves alot more research.
Casey (June 25, 2020 8:13 PM)
My blood type is Rh negative O negative it think that's how the doctors said it. Have there been a lot of people with Rh negative blood getting sick with covid-19 but I still have O negative.
Kim (June 26, 2020 2:41 PM)
I’m also rh-. That is not our blood type though. O- is your blood type(I’m also o-.) we just lack the The factor in our blood which all negative individuals do regardless of their letter type. The rh factor at this time does not look to be relevant in regards to covid risk of infection or severity
Agustin (June 26, 2020 5:47 PM)
Hello There
I am B- (52 years old but healthy) I and my Doctor are 99% sure I had the virus in late March, lost my sense of smell and taste (total) for 4 weeks, 10-12 days I sweated a lot, tired a lot, could sleep 12 hours nonstop, never affected my lungs (two other friends in the building also got sick, lost the sense of smell and taste for 2-3 weeks, but developed more flu symptoms, but like me, we all 3 had never lost the sense of smell and taste) got tested 10 weeks later and came back negative (swab) but a friend sent me the tester for antibodies, did two of them and was with high antibodies....are people with B- in more danger? Sincerely Agustin
Stacy Gonzalez (June 29, 2020 4:38 AM)
Have you have any information for thr RH Negative blood type by any chance? (Where we might fall in the category)
CeeCie (June 29, 2020 5:22 PM)
Could this research make a case for giving O- blood to A, B, & AB, COVID19 patients? Might the type O blood help the effects of the disease be less detrimental to the other blood type patients?
Kimberly Borneman (June 29, 2020 8:50 PM)

I have THE SAME QUESTION I AM RH NEGATIVE AS WELL
Araceli Cortez (June 30, 2020 2:21 PM)

I am o+ and have some of the symptoms my fever has reached 103 and iam diabetic have an ironand vitamin D difficiency and a low immune system will i get severe symptoms 😢 of covid 19

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