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Genes, Blood Type Tied to Risk of Severe COVID-19

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SARS-CoV-2 virus particles
Caption: Micrograph of SARS-CoV-2 virus particles isolated from a patient.
Credit: National Institute of Allergy and Infectious Diseases, NIH

Many people who contract COVID-19 have only a mild illness, or sometimes no symptoms at all. But others develop respiratory failure that requires oxygen support or even a ventilator to help them recover [1]. It’s clear that this happens more often in men than in women, as well as in people who are older or who have chronic health conditions. But why does respiratory failure also sometimes occur in people who are young and seemingly healthy?

A new study suggests that part of the answer to this question may be found in the genes that each one of us carries [2]. While more research is needed to pinpoint the precise underlying genes and mechanisms responsible, a recent genome-wide association (GWAS) study, just published in the New England Journal of Medicine, finds that gene variants in two regions of the human genome are associated with severe COVID-19 and correspondingly carry a greater risk of COVID-19-related death.

The two stretches of DNA implicated as harboring risks for severe COVID-19 are known to carry some intriguing genes, including one that determines blood type and others that play various roles in the immune system. In fact, the findings suggest that people with blood type A face a 50 percent greater risk of needing oxygen support or a ventilator should they become infected with the novel coronavirus. In contrast, people with blood type O appear to have about a 50 percent reduced risk of severe COVID-19.

These new findings—the first to identify statistically significant susceptibility genes for the severity of COVID-19—come from a large research effort led by Andre Franke, a scientist at Christian-Albrecht-University, Kiel, Germany, along with Tom Karlsen, Oslo University Hospital Rikshospitalet, Norway. Their study included 1,980 people undergoing treatment for severe COVID-19 and respiratory failure at seven medical centers in Italy and Spain.

In search of gene variants that might play a role in the severe illness, the team analyzed patient genome data for more than 8.5 million so-called single-nucleotide polymorphisms, or SNPs. The vast majority of these single “letter” nucleotide substitutions found all across the genome are of no health significance, but they can help to pinpoint the locations of gene variants that turn up more often in association with particular traits or conditions—in this case, COVID-19-related respiratory failure. To find them, the researchers compared SNPs in people with severe COVID-19 to those in more than 1,200 healthy blood donors from the same population groups.

The analysis identified two places that turned up significantly more often in the individuals with severe COVID-19 than in the healthy folks. One of them is found on chromosome 3 and covers a cluster of six genes with potentially relevant functions. For instance, this portion of the genome encodes a transporter protein known to interact with angiotensin converting enzyme 2 (ACE2), the surface receptor that allows the novel coronavirus that causes COVID-19, SARS-CoV-2, to bind to and infect human cells. It also encodes a collection of chemokine receptors, which play a role in the immune response in the airways of our lungs.

The other association signal popped up on chromosome 9, right over the area of the genome that determines blood type. Whether you are classified as an A, B, AB, or O blood type, depends on how your genes instruct your blood cells to produce (or not produce) a certain set of proteins. The researchers did find evidence suggesting a relationship between blood type and COVID-19 risk. They noted that this area also includes a genetic variant associated with increased levels of interleukin-6, which plays a role in inflammation and may have implications for COVID-19 as well.

These findings, completed in two months under very difficult clinical conditions, clearly warrant further study to understand the implications more fully. Indeed, Franke, Karlsen, and many of their colleagues are part of the COVID-19 Host Genetics Initiative, an ongoing international collaborative effort to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes. Some NIH research groups are taking part in the initiative, and they recently launched a study to look for informative gene variants in 5,000 COVID-19 patients in the United States and Canada.

The hope is that these and other findings yet to come will point the way to a more thorough understanding of the biology of COVID-19. They also suggest that a genetic test and a person’s blood type might provide useful tools for identifying those who may be at greater risk of serious illness.

References:

[1] Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Wu Z, McGoogan JM, et. al. 2020 Feb 24. [published online ahead of print]

[2] Genomewide association study of severe Covid-19 with respiratory failure. Ellinghaus D, Degenhardt F, et. a. NEJM. June 17, 2020.

Links:

The COVID-19 Host Genetics Initiative

Andre Franke (Christian-Albrechts-University of Kiel, Germany)

Tom Karlsen (Oslo University Hospital Rikshospitalet, Norway)

66 Comments

  • GA Peach says:

    Why are all these people asking for medical advice in the comment section of this article??!?!?!?!?!?!

  • Carol says:

    Seems to make sense, well done, looking forward to more news on this subject

  • Darlene B. says:

    We are interested in your studies regarding the severity of the covid19 virus on individuals with type A and type O negative blood since this relates to my husband and me.

    • Kimberly says:

      Me Too! I want to know how many people who are Rh Negative have had Covid-19 and how many people who were Rh Negative have died from Covid-19 too!

      • Mike Norris says:

        I am disappointed that few are paying much attention to Rh factor in these statements. Within the primary research that the above information references is a further reference that essentially posits that Rh factor is a dominant indicator of risk. You can find this information here: Zietz M, Tatonetti NP. Testing the association between blood type and COVID-19 infection, intubation, and death. April 11, 2020 (https://www.medrxiv.org/content/10.1101/2020.04.08.20058073v1. opens in new tab).

      • Stacey says:

        Me too! Please let me know if you find any information on RH negative in regards to Covid.

  • Bulelwa Mnyanda says:

    Quite interesting and makes sense.

    • Cyndi Mc. says:

      My blood type is 0-, rh- . I heard that people who’s rh- are resistant to certain viruses. Is there any truth to that?

  • Marilyn Novak says:

    This virus has so many facets, with the blood clotting one being among the most frightening. Hopefully what we learn will help us when we experience the next pandemics, as it is difficult to imagine us being able to convince people with the custom of eating wild animals to give it up.

  • Brenda S. says:

    My father in law is 94. He lives in a nursing home. He had 2 positive tests then a negative result came today. He is B+ blood type.

  • Dianne Davies says:

    What about AB blood groups are they at risk?

  • Kathleen L. says:

    I have AB negative blood type. It is the rarest blood type, I am more likely to get sick if I contract the coronavirus?

  • Heather K says:

    Does the Rh factor make a difference also? Is A+ at a higher risk than A- blood type?

    • Andrea O. says:

      I have Type O blood (read the NEJM article) My question is about how likely it is for this blood type to be an asymptomatic carrier, possibly endangering others more than oneself.

  • Ram says:

    My Blood Group is AB+ve ,four days back I got cold and fever after three days symptoms Normal. I don’t know what’s happened

    • Brian J Wheeler says:

      As I read this, the denominator of the ratio of type O victims of Covid-19 would not include the people who had very mild, asymptomatic cases and therefore never sought testing. In other words, the percentage benefit to type O people may be bigger than the numbers suggest. Is this a legitimate observation?

  • J Carr says:

    if AB have no antibodies, how do vaccines work and are there the gene and blood tests available now?

  • Chrystal says:

    Im am A- Rh negative I have never had a virus ever in my life I have never had the flu and don’t get any Vaccines. I avoid modern Medicine if at all possible. I have been around a positive covid Patient and never contracted the virus I tested negative.
    Is it possible that there are some folks that could have a immunity?

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