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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)

91 Comments

  • Herb says:

    There are 5 members of our household, myself, my wife and 3 adult daughers. Covid went through our house. Everyone had strong symtoms but me. I’m O+

    • Brigit says:

      I was exposed to both my teenagers over a period of time. They both tested positive for covid and I tested negative twice. I did get some strange symptoms at the time but continued testing neg for virus and tested neg for antibodies. I have O- Neg blood. Very bizarre and perplexing for me

  • Ken says:

    My wife and I (both A+ blood type and both 70 yrs old) tested positive in early July 2020. She spent 8 days, and I spent 11 days in hospital. My O2 was at 77% when I went by ambulance. Really did not think I was going to make it out. Came home with 02 for 2 months 24/7. Fast forward to Jan 2021. Got 1st Moderna shot. 12 hrs later: nausea, teeth chattering chills, hot sweats, and every joint and muscle ached. Could not get out of bed next morning. Took 800 mg Ibuprofen and was able to slowly get up 45 min later. By 3rd day I was back to normal but extremely fatigued. 2nd shot on Feb 14th. Same symptoms but much, much milder. Wife went thru same but much less severe on all fronts.

  • Gwen S. says:

    Was wondering if PF4 blood factor has any protection against severe Covid. I have that and thus far no covid and no reaction to vaccine. I know I can’t get Malaria with that blood factor. Just curious.

  • Joy M. says:

    On Thanksgiving Day I had a runny nose. I worked the next day and was off the weekend. I thought I had a sinus infection so I took medication for those symptoms. Only ran a low grade temp on Friday of 99 degrees. I worked with no symptoms Monday and Tuesday and had routine heck at work where I found out I had COVID. I was in disbelief. My symptoms were mild. I’m a 48-year-old woman. My husband’s symptoms were similar and our daughter did not contract it.

  • Eve E. says:

    Has there been any research done on whether increased severity of Covid-19 symptoms in blood type As is associated with whether or not the individual is homozygous or heterozygous? Are homozygous type A blood type individuals at higher risk than heterozygous type As?

  • J.Smith says:

    I’m type O- and lost my entire sense of taste and smell in mid December 2019. I also had a week long spate of gastro-intestinal symptoms and strange dreams (no fever or SpO2 issues). I thought it was due to the CBD isolate I was using for diabetic nerve pan in my feet (I’m 78 and have diabetes, heart failure, and cancer) but am otherwise in good physical condition for my age and underlying co-morbidities (6′ – 3″, 205 lbs, and can bench press 175 lbs. (50 reps)). I’m just now able to smell (~60%) and taste (~80%), but both are off and on. I’m fully immunized with the Moderna Vaccine as of 03/26/2021, and believe the vaccine improved my 1+ year “long covid” symptoms. Who may know? My entire family have type O- blood and have experienced similar loss of taste and smell episodes but no severe Covid-19 illness! I concluded by March 2020 that I was blessed with Type O-Neg Blood! The foregoing is for what it is worth to any readers.

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