Blood Type, Genes Linked to Covid-19 Risk



PERVASIVE good news about the O positive blood group—along with other possible genetic markers of health and disease—usually turns out to be a mixed bag. But recent studies on Covid-19 patients that link blood types and genetic markers to the risk of serious disease are helping explain why some people get sicker than others—and may ultimately contribute to using better drugs to fight the illness.

For Covid-19, type O blood reduced susceptibility to the infection but did not correlate with lower rates of hospitalization or death following infection—in a Danish study that compared blood from over 473,000 people infected with Covid-19 to that from more than two million in the general population.

A “slightly increased infection prevalence among non-O types” was the finding in a different study at the New York Presbyterian hospital system on 14,112 individuals who tested positive for Covid-19 infection. Importantly, in that study, Rh-negative blood type had a “protective effect” for all risks — of infection, intubation and death.

(Compared to those with O type blood, risk of intubation decreased for those with A type, and increased among AB and B types in this study. And risk of death increased for type AB and decreased for types A and B. In another study, those with type A were at higher risk of severe infection.)

Blood type is vital information for people needing transfusions; the wrong type is likely to trigger rejection, followed by severe reaction and even death. Each person’s blood type depends on the kinds of antigens or protein molecules on the surface of red blood cells—with four types in the “ABO system,” A, B, AB and O—which are involved in detecting unwanted or foreign cells.

The other system, referred to as Rh, indicates the presence or absence of a different molecule on the red blood cells called the Rhesus factor, which makes an individual’s blood type either positive or negative. The most prevalent blood type is O positive —found in 37% of the population, followed by A positive in 34%, down to the least common type, AB negative.

With the first SARS coronavirus, decreased susceptibility to infection may have occurred in patients with types O and B blood—with the possible explanation that anti-A antibodies blocked interaction between the virus and receptors in the cell, thus preventing transmission.

Among blood-type risk factors linked to Covid-19, venous thromboembolism (obstruction of a blood vessel by a clot) is more common among those with non-O blood types, as is coagulopathy (impaired ability of the blood to clot). But the latter may also be a downside following severe trauma: in a recent Japanese study, those with type O blood appeared to be at higher risk for death, perhaps due to reduced levels of blood clotting factors.

Those with non-O type blood are at higher risk for high blood pressure, high cholesterol and stroke due to disrupted blood flow to the brain. Coronary artery disease also occurs more often in these groups who have the ABO gene (sometimes confusingly referred to as ABO type blood) responsible for blood types A, B or AB. “If you have the ABO gene and you live in an area of high pollution, you may be at greater risk of heart attack,” explained New Jersey oncologist Douglas Guggenheim.

Those with the ABO gene are also more likely to develop Type 2 diabetes, compared to those with type O blood. An 18-year study of more than 82,000 female French teachers found 3,553 women diagnosed with Type 2 diabetes. Compared to those with blood type O, those with type A were 10% more likely to develop the disease and those with type B, 21% more likely.

Among other diseases, malaria infections are less likely to cause symptoms in people with type O blood. But those with type O tend to have higher levels of stomach acid and may be more prone to infections with the bacterium that causes stomach ulcers, Helicobacter pylori.

(The latter was one explanation in once-popular theories about a “blood-type diet” for why those with type O blood do better eating high levels of animal proteins. But skeptics have pointed to the lack of supporting research for these diets and trace any benefits to the universal recommendation to avoid processed food—making all of the diets based on blood type healthier than what most people eat.)

For Covid-19, additional genetic links include several sites on chromosome 3 associated with respiratory failure in critically ill patients. Recent studies also found genetic variants located close to genes involved in the interferon immune response, suspected to play a role in life-threatening Covid-19 infections.

But only a “chunk of the answer is in our genes,” said University of Edinburgh Covid-19 researcher Sara Clohisey. The likely combination of factors involved includes age, obesity and gender—though in men, who are more likely to die of Covid-19 than women, genetic variants related to sex have not yet shown up in these studies.

A recent example of the limited role of genetic inheritance in Covid-19 infections was a pair of identical twins, who contracted the infection from the same individual at the same time, exhibited the same symptoms and had similar vital signs and lab test results. But soon after admission to the same hospital, one twin went home while the other ended up in the ICU, needed a respirator, developed septic shock and took another month to recover.

Rather than genetic inheritance, the best explanation for different responses in monozygotic twins (who develop from one fertilized egg divided in two) is gene expression—epigenetic differences. In another case of twins, one developed a malignancy and the other did not, despite carrying a gene that put them both at risk.

(Epigenetics may also be the explanation for physiological differences observed in astronaut Scott Kelly—compared with his identical twin brother Arizona Senator Mark Kelly—after spending time on the International Space Station. As for whether blood type itself can change, the only possible explanation is a bone marrow transplant.)

For O positive type blood, the most pervasive bragging rights are patently unfounded: people with this type blood are not universal donors—able to give blood to everyone, regardless of blood type.  That would be O negative, highly valued because it is found in only about 6% of the population.

And those with AB+—also rare, making up less than 4% of the population—are universal recipients, able to receive blood of every type. People with any Rh-negative blood type can donate to someone who is Rh-negative or positive; but a person who is Rh-positive can donate only to someone who also has Rh-positive blood.

—Mary Carpenter

Well-Being Editor Mary Carpenter keeps us updated on Covid-19. To read more of her posts, click here.

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