It has been proven that millions of people in Germany were infected with Sars-CoV-2 in the Omicron wave. However, some people have never had a positive test result before. What can be the reason?

The impacts came more and more frequently and closer: Corona hit friends, their children, grandparents, most of the work colleagues. For people who have been spared so far, their own corona infection in the past few months has often only seemed a matter of time.

However, some have withstood the omicron wave that is currently subsiding with millions of infected people nationwide, i.e. in more than two years of the pandemic they have still not knowingly been infected with Sars-CoV-2.

If you ask people who count themselves as part of the group, you hear a whole range of assumptions about possible causes: Do regular long subway rides possibly become harder because you keep getting small amounts of the virus? To anticipate: “This thesis falls into the realm of speculation,” says the Essen virologist Ulf Dittmer.

Lucky or already infected?

Other people who have not yet been infected give themselves good marks for complying with the corona rules. Some simply consider themselves lucky because they would not have been infected either from a later positive contact person or from visiting a club. Some doubt whether they already had the virus, just unnoticed and unconfirmed. For example, in the days when tests were hardly available. Or when you had symptoms but the tests never worked. It cannot be ruled out that it was due to incorrect sampling or timing.

Scientific approaches to explaining the question go deeper. However, there is no definitive answer that explains non-infection. Rather, the key may lie in a combination of different circumstances. “There are a few hypotheses that seem plausible,” says Leif Sander, who heads the Infectious Diseases Clinic at the Berlin Charité.

Many unnoticed infections

First of all, one has to consider that a not inconsiderable proportion of cases go largely or completely unnoticed. In an overview paper from the end of 2021 in the “Jama Open Network”, the authors summarized that even in the case of confirmed corona infections, around 40 percent had no signs of illness at the time of the test. The basis was almost 100 different international studies with data from a total of around 30 million people.

Against this background, the test frequency plays a role in the detection of infections. Those who test infrequently are more likely to miss a very mild or asymptomatic infection. With frequent testing, mild cases are more likely to be detected.

Genetic Traits

Apart from that, genes can also play a role. “There are people who, due to genetic characteristics, are difficult to be infected with malaria or HIV, for example. To a certain extent, this will also apply to Sars-CoV-2, »says Sander. However, the genetic factors are not fully understood.

As Ulf Dittmer, Director of the Virology Institute at Essen University Hospital, explains, the genetic make-up of the immune system – so-called HLA molecules – plays an important role in protecting against Covid-19. And blood groups not only influenced the severity of the disease, but perhaps also the transmission of Sars-CoV-2.

vaccination protection

Vaccination protection is probably often underestimated: the level of antibodies in the blood, which can render harmless corona viruses that have penetrated the body, drop in the period after the vaccination. “However, the protection remains significant for months. That also still reduces infections,” says Sander.

Immune responses to vaccination also differ from person to person. “If the answer is particularly good, the combination of vaccination and a previous infection with one of the four common cold coronaviruses can also play a role,” the Charité professor points out.

Virologist Dittmer says that it is now known that a special subclass of antibodies provides particularly good protection against corona infection. “However, the measurement is complicated, so for the time being no one will know whether they have these antibodies or not.”

More activated immune system in children

According to Sander, children have the phenomenon that they generally have a more strongly activated innate immune system, so to speak, the immune system is often pre-activated. In addition, there is the effect that people are generally less susceptible to the next lurking pathogen for a few days immediately after an infection. “One of the reasons for this is the so-called interferons, special antibodies in the mucous membrane, which also reduce the susceptibility to Sars-CoV-2 in the event of contact in the time window.”

Another conceivable factor: In some people, the immune system may throw the virus out of the body very quickly, as Sander says. “In a Swedish study, researchers found specific T cells in people who did not become positive after contact with infected household members – a sign that their immune system has definitely dealt with Sars-CoV-2, even if an infection and also Antibodies against the virus were not always detectable.”

What follows? Anyone who thinks they have been spared so far could already have the infection behind them. Or have benefited from certain temporary effects, as yet unknown genetic factors and coincidences. Sanders conclusion: “The fact that you have not had Corona before does not mean that you are safe for all time. It can look completely different with a new virus variant or depending on the situation.”