Why do some people just not get it?

Some have to go to the hospital, others are spared. Apparently the genes, previous infections and blood type have something to do with it.

Crowds of people meet in the Hallenstadion Zurich, infections are likely – but not for some people.

Ennio Leanza / Keystone

Imagine not having to worry about getting infected – because you were born with natural immunity to the Sars-CoV-2 coronavirus. With this superpower you would not only have a more relaxed life, you would also be in great demand as a research guinea pig.

Immunity to the coronavirus is currently a much-researched field. Scientists around the world are looking for people who have been shown to be resistant to the virus. The researchers want to use them to find out why Corona is so unfair: some people have been infected for the second or third time, or the virus knocks them out so much that they have to be treated in the hospital. Others, sometimes even very old people, are not affected at all or only mildly, despite repeated contact with the sick.

This was shown very impressively by an ethically controversial experiment from 2021, in which British doctors intentionally infected 34 young and healthy people with a small dose of corona viruses. 18 of them fell ill with mild symptoms, the researchers could not prove any infection in the other 16. It is unclear whether the test subjects really did not become infected or whether their immune system was able to fight the virus very early on.

Explanation No. 1: nothing noticed

So what distinguishes those who are hard hit by the virus from those whose immune systems seem to nip it in the bud quickly? Scientists have various hypotheses as to the mechanisms behind the phenomenon.

For those people who have been triple vaccinated and who are wondering why they are being spared, the most obvious thing is probably: they have already been infected unnoticed. Your immune system was able to limit the proliferation of the virus so much that a quick test did not even work because of the low viral load.

Explanation #2: previous infections

“Another explanation is cross-immunity,” says Alexandra Trkola, a virologist at the University Hospital of Zurich. Four other corona viruses, so-called HCoVs, have been circulating in the population for a long time and cause harmless colds. Various studies have shown that people who do not contract Sars-CoV-2 despite being at high risk are more likely to have certain T cells. These formed beforehand during an immune reaction against the HCoVs, but apparently also protect at least partially against Sars-CoV-2.

T cells are white blood cells and seek out virus-infected cells to destroy them. A few months ago, the virologist Alexandra Trkola was able to show in a study that another part of our immune system, the antibodies, not only protect against the harmless corona cold viruses, but also against Sars-CoV-2.

“These findings may help us in the development of new drugs and vaccines,” says Trkola. If effective T cells or antibodies could be injected in the future, people would probably be at least partially protected against almost all corona viruses that are in circulation. “Such a drug would probably even be helpful against completely new corona viruses.”

Explanation #3: genetic differences

Scientists around the world are looking for genetic quirks that make people resistant to the virus. Very few people are completely immune, but so far 15 gene segments have been discovered that seem to play a role. These are mostly responsible for the production of certain enzymes that are important for the immune system. For example, changes in the gene for the so-called ACE-2 receptor can lead to the virus being less able to penetrate cells.

A similar mechanism is known from the HI virus: Around one percent of humanity lacks the receptor that the virus needs to infect the cells. These people are protected against HIV infection. “This is not to be expected with Covid-19 because the ACE-2 receptor in the body performs important tasks and it is almost never absent,” explains virologist Trkola. But even small changes in the gene could result in greater resistance to infection with corona.

Explanation #4: the blood type

One of the 15 gene segments that have a decisive influence on the immune response to Sars-CoV-2 also determines the human blood group. The molecular biologist Andre Franke from the University of Kiel, together with Norwegian researchers, published a large study in the New England Journal of Medicine, which made waves in 2020, the results sounded so implausible: People with blood group A have the highest risk of a severe course, People with blood group 0, on the other hand, have the lowest. They also seem to get infected less often. In the meantime, the results have been repeated and confirmed by Danish and American studies.

The connection probably lies in the compatibility of the blood groups with each other: in the blood, the red blood cells carry different antigens. People with blood group A carry A antigens, blood group B has B antigens. People with blood group 0, on the other hand, don’t wear any at all. That is why a person with blood group 0 can donate his blood to everyone else, but conversely he cannot tolerate their blood because his immune system rejects the antigens.

French researchers from the University of Nantes are now suggesting in a study that the virus transmission works according to the same principle: a person with blood group 0 cannot easily become infected with people with other blood groups. But once infected, it can very easily infect others. This works because the coronavirus picks up their molecules as it multiplies in our cells. If blood group antigens from foreign blood groups are present, they immediately trigger a reaction in the immune system, which then also fights the virus.

Search call by researchers

Anyone who is now convinced of himself that he is one of those special immune people who can respond to a search call from scientists around the Greek immunologist Evangelos Andreakos, who wants to find genetically protected people. We are looking for so-called discordant couples, in which two people have shared a bed and home and only one has been infected – documented by regular tests. Perhaps the knowledge of one’s own immunity actually gives some people some peace of mind.