It has been more than two years since the start of the global COVID-19 pandemic. Throughout that time, for some people, the infections became more frequent and hit closer to home. Their friends contracted coronavirus, and sometimes their children, grandparents and most of their co-workers too. It seemed to be only a matter of time before they would contract the virus as well but their luck never ran out it seems as if some people have never been knowingly infected with COVID-19 in over two years even after the wave of infections caused by the highly transmissible omicron variant.

If you ask them the reason, you'll hear all sorts of suppositions. For example, regular long trips on the underground will build up your resistance by repeatedly exposing you to small viral loads.

"This hypothesis falls in the realm of speculation," says Dr. Ulf Dittmer, director of the Institute of Virology at Essen University Hospital in Germany.

Some people not previously infected attribute it to scrupulously following COVID-19 precautions. Others thank their lucky stars for not contracting the virus from a contact person who later tested positive or while they partied at a club. Still, others wonder if they had an asymptomatic infection that wasn't detected, for instance before testing was widely available. Or maybe they did have symptoms but tested negative because the sample was collected improperly or the timing was inopportune.

Scientific attempts at an explanation go deeper, but there's no single definitive answer as to why some people still haven't caught COVID-19. A combination of factors could be the reason.

"A number of hypotheses appear plausible," says Dr. Leif Erik Sander, director of the Department of Infectious Diseases and Respiratory Medicine at Charité University Hospital in Berlin.

First of all, it's important to bear in mind that a significant number of COVID-19 infections go largely or completely unnoticed. In a systematic review and meta-analysis published late last year in the Journal of the American Medical Association (JAMA) Network Open, the authors noted that about 40% of people with a confirmed COVID-19 diagnosis were asymptomatic at the time of the test. The finding was based on 95 international studies involving nearly 30 million people.

The frequency of testing obviously plays a role in detecting infections. If you're not tested regularly, there's a greater chance you won't become aware of a mild or asymptomatic infection.

And your genes can play a role too in whether or not you get COVID-19.

"There are people who, owing to genetic characteristics, can't easily be infected with malaria or HIV (the virus that causes AIDS), for instance. In certain gradations this will also be true of Sars-CoV-2," says Sander, adding that the genetic factors aren't completely understood, however.

As virologist Dittmer explains, human leukocyte antigens (HLA) molecules, which are encoded by a complex of genes, play an important part in the body's immune response to pathogens such as Sars-CoV-2. He adds that a person's blood group, too, not only influences disease severity but perhaps also susceptibility to infection with the virus.

The protection provided by vaccinations is probably often underestimated. Although levels of antibodies in your blood able to bind to and neutralize invading coronaviruses decline some time after injection with a vaccine, "protection nevertheless remains significant for months," Sander says. "That, too, reduces infections."

Immune responses to COVID-19 vaccines vary from person to person. "If the response is especially good, vaccination in combination with a previous infection with one of the four endemic common cold coronaviruses can also play a role," he suggests.

According to Dittmer, a particular subclass of antibodies has been found to provide especially good protection from a novel coronavirus infection. "Measuring them is complicated though, so for the time being no one will know whether they've got these antibodies or not," he says.

The fact that children who get COVID-19 tend to have either no or only mild symptoms is down to their generally having an innate immune response that's stronger than the immune response of adults, according to Sander. It's often "preactivated," so to say.

Another phenomenon worth mentioning is that for a few days after getting an infection, people are typically less susceptible to infection with another pathogen. "This is due in part to interferons, which are defensive proteins in mucous membranes that also reduce susceptibility to Sars-CoV-2 in the event of contact with it in that time window," Sander says.

He also notes that some people's immune system may rid their body of the virus very quickly: "In a Swedish study, researchers detected specific T-cells (a type of white blood cell that's part of the immune system) in people who didn't test positive after contact with infected household members – a sign their immune system had indeed engaged Sars-CoV-2 even though an infection or antibodies against the virus weren't always detectable."

So what are we to conclude? If you think you've somehow managed to skirt a COVID-19 infection, you may already have one behind you. Or you may have benefited from certain temporary circumstances, as-yet-unexplained genetic factors and/or dumb luck.

"Just because you haven't had COVID-19 yet doesn't mean you're permanently safe," Sander warns. "A new coronavirus variant, or a different set of circumstances, can totally change that."