Can people be naturally immune or resistant to COVID-19?

More than two years into the COVID-19 pandemic, most Americans have some immunity against the virus — either by vaccination or infection, or a combination of both. But there have been some rare cases in which certain unvaccinated people seem to have been able to dodge the virus despite being repeatedly exposed to it. This has raised the question of whether it is possible that some people are simply immune or resistant to COVID-19 without having had the virus or a vaccine.

Yahoo News spoke with three experts about whether such resistance to COVID-19 exists and how it would work.

Video transcript

CATHERINE TROISI: We're still investigating why it seems that some people are not getting infected. And I think there are a couple of potential explanations, all of which might be true in certain circumstances. One is that you've just been lucky. We rarely know, unless it's a household member, who we got COVID from. So maybe you just haven't been exposed or you've been exposed at low levels. That's one explanation.

The other explanation, which I think probably accounts for a fair proportion of these cases, are that you have had it. We know that a lot of cases are asymptomatic. You aren't sick, so you don't know that you had it. So that probably accounts for some of them as well.

And then there's this idea of cross-immunity. COVID is a coronavirus, as we know. And there are other coronaviruses that cause the common cold. In fact, about 30% of common colds are thought to be caused by these other coronaviruses.

SHANE CROTTY: When we say common cold, the word common is the most important part of that. There are probably 200 common cold viruses, of which four are coronaviruses. So it's not-- the sniffle I had two years ago probably wasn't a coronavirus, it was probably one of these other 200 cold viruses. But everybody's had these common cold coronaviruses at some point.

CATHERINE TROISI: And there is some evidence that at least some people have some immunity because they've seen a different coronavirus, but it's still the same family. That may account for part of it.

SHANE CROTTY: Main idea there would be t-cell responses that certain people happen to make in response to certain coronaviruses they've had before that may provide a degree of protection that other people just don't happen to have.

CATHERINE TROISI: The other possibility that we're investigating, but we know happens with other viruses, is that there are genetic differences between people, particularly with their immune systems. So some people just seem to be immune. They can be exposed to a virus and won't get sick.

NEVILLE SANJANA: I think there's actually some good historical precedent for this kind of thing. So I think the clearest example that we know, this is because there's been such a tremendous research effort, is with HIV/AIDS. And so there, we know that there's an entry receptor, similar to the one that we've identified for SARS-CoV-2, but it's a different gene. So there with HIV, the virus that causes AIDS, the entry receptor is CCR5.

And we know that there are some people have naturally have a mutation that gets rid of CCR5. They just don't express CCR5. And this leaves them virtually immune. I think there's a few things you can say about genetic factors with COVID-19. So if you look at the example of other viruses, one thing you might first think about is what's the entry mechanism? What's the entry receptor?

And so with the virus that causes COVID-19 with SARS-CoV-2, it's going to be ACE2. And so one thing that is worth looking into is whether these folks might have mutations in the ACE2 receptor that just make it harder for the virus to get in. Another thing that might be interesting is other genes across the genome.

So the human genome has about 20,000 genes in it. And some of those genes might make us more or less vulnerable to COVID-19. I think the reason we want to study these exceptional responders or to understand what genes modulate the virus' ability to get into the cells and infect the cells is by finding those genes, understanding that biology, even in people that maybe don't have a mutation in that gene or nearby that gene, we could still use that insight to develop next generation therapeutics.