Since the coronavirus pandemic emerged, people have been scrambling to understand what puts them at risk.
And when studies began to surface suggesting that blood type and Covid-19 might be intertwined, the connection attracted immediate attention.
"There are two questions," Mypinder Sekhon, an intensive care physician at Vancouver General Hospital. tells Inverse. "One is susceptibility for getting infected with SARS-CoV-2 and the other is developing severe Covid-19."
On Wednesday, two studies were released in the journal Blood Advances that address each one.
The first study suggests people with type O blood may be less susceptible to Covid-19. That's based on an analysis of 473, 634 people tested for Covid-19, and a control group of about 2.2 million people. Of these, 38.4 percent of people with Covid-19 had type O blood, significantly less than the 41.7 of people in the control population who had that blood type — a result that implies they may be slightly less likely to test positive.
Michael Barnkob, the study's first author and a doctor at Odense University Hospital, points out that people with type O blood are not immune to the virus in any way. But he adds that the study clarifies whether blood type influences who may get the disease in the first place.
"These are not massive differences in risk, but they do suggest some interesting biology is at work," he tells Inverse. "With some confidence we can now say that blood type does affect your chance of contracting the virus, but not that it affects the severity of disease following infection."
That's where the second paper, co-authored by Sekhon, comes in.
That research shows blood type is linked to more severe forms of Covid-19. The paper focuses on 95 critically ill people with Covid-19. It suggests some 84 percent of those with type A or B blood needed ventilators to battle the illness. Only 61 percent of people with type O blood ended up on ventilators. People with type O or B blood also only stayed in the intensive care unit for nine days, compared to people with type A blood, who stayed for 13.5 on average.
There are other studies that complicate the picture, suggesting there is not connection between disease outcome and blood type (like this paper, produced by scientists at Massachusetts General Hospital).
The research on blood type and Covid-19 is still preliminary.
But here's where we stand right now.
Blood type and getting Covid-19
Barnkob's paper isn't the only one to suggest a connection between blood type and less susceptibility to Covid-19. A meta-review published in July also found that type O blood was linked to lower likelihood of infection.
The new study can't quite explain why this may be the case, but Barnkob has a few working ideas that all come down to the structure of blood itself.
Blood is comprised of two parts: plasma (yellowish stuff that's filled with proteins like antibodies) and red blood cells.
The blood cells, like the cells that make up other tissues in the body, are covered in surface markers. Those surface markers are sugars that differ in structure depending on what type of blood you have. For example, someone with type A blood will have a slightly different sugar molecule on their blood cell compared to someone with type B blood. The letter connotes which sugar molecules are present: people with the AB blood type have both, people with O have neither.
People can also have a surface protein on their blood cells called the Rhesus factor. The plus and minuses seen on blood types references the presence of that Rhesus protein.
Put all those things together and you end up with eight different blood types: A+, A-, B+, B-, O+, O-, AB+, AB-.
To take things one step further, there are also antibodies present in the plasma portion of each person's blood. Someone with type A blood will actually have have anti-B antibodies in plasma: the antibodies sensitive to the incompatible blood type. Type O blood has neither A nor B-style sugars on the red blood cells, but it does have anti-A and anti-B antibodies in the plasma.
The coronavirus, suggests Barnkob, may be reacting differently to these surface factors and the antibodies present in each person's blood type.
"If virus particles are made in a blood type A individual, then that virus particle is coated with A sugars," he explains. "If this virus particle infects an O-type individual, he or she will have antibodies against A and B sugars, and be less likely to become infected."
That's just one theory. Barnkob also suggests the virus may simply be better at binding to cell surfaces with type A and type B sugars on them.
Angelico Mendy, a professor at the University of Cincinnati College of Medicine, tells Inverse another theory is worth exploring in future research, too. It's possible that anti-A antibodies (the kind present in non-A blood types) may prevent the coronavirus from binding to cells in the first place.
"[A] patient with type A blood who do not have the anti-A antibodies would be at higher risk, while those with O blood who have the anti-A antibodies seem to be protected," he says.
But if that were the case, scientists would also expect to see protection in people with type B blood as well as type O, something that, he notes, hasn't clearly documented.
Finally, the connection may also involve the Rhesus protein. A study recently accepted for publication (but a pre-print, for now) on 1,559 people at New York Presbyterian Hospital, noted that people who lacked Rhesus protein (the - attached to their blood type) also had 2.7 percent lower risk of infection with Covid-19.
It's not just that paper. Another paper, this time, on 1,289 adult patients from Massachusetts General Hospital found people with B+ and AB+ blood types were more likely to test positive for the virus, again suggesting the picture is more complicated than it might appear.
"Our work can perhaps inspire scientists to look more closely in these directions: some work in cell lines do indicate that the first two hypotheses might have some legs," says Barnkob.
Blood type and severe Covid-19
Though some papers have found no connection between blood type and severity of disease. For instance, Mendy is the author of a pre-print paper that examined 428 patients with Covid-19. His results showed that blood type didn't affect who ended up in the hospital or who ended up in the intensive care unit.
Sekhon cautions that it's too soon to write off a connection completely.
Other studies, like the July meta-analysis also hinted people with type O blood may suffer from less severe disease compared to other blood types.
Sekhon believes his study sample was broad enough to suggest a clear pattern:
"Our population covers about 90 percent of overall COVID-19 emissions within the province of British Columbia so represents quite a diverse and large population," he says.
There are other theories that warrant investigating, he says. People with type O blood actually have less Von Willebrand factor (a protein which helps with clotting) in their blood. People with types A and B blood have as much as 25 percent more of that factor, which could be linked to severe Covid-19 side effects like blood clots.
"We do know now that patients with Covid-19 are at higher risk of developing blood clots which can have adverse effects on organ function. So that may be a plausible mechanism," he says.
But there needs to be a bigger study, preferably one conducted across countries, to help solidify the connection between severity and blood type.
"The other essential step is to repeat these observations," Sekhon says.
For now, it's clear that blood type doesn't outweigh risk factors like age or pre-existing conditions. But it's something that scientists are keeping an eye on.