RACHEL MARTIN, HOST:
Maybe you know these people. They're your neighbors or your friends or your family, people out there who seemingly have just dodged COVID completely. Joining us to talk about this phenomenon is NPR health correspondent Michaeleen Doucleff. Thanks so much for being here.
MICHAELEEN DOUCLEFF, BYLINE: Thank you for having me.
MARTIN: So at this point, it feels like most of us have had at least one bout with COVID. But there is that someone in our lives and you're like, what superpowers do you have that you have not contracted this thing yet?
DOUCLEFF: Exactly. You know, for me, it's this guy named Joe Esparza. I live in Alpine, Texas, now, and he owns the print shop here. And I was talking to him about this, and he told me his entire family has had COVID at different times.
JOE ESPARZA: My first experience with it was when my eldest son got it.
DOUCLEFF: Then his other son got sick.
ESPARZA: Step and repeat. It all happened again.
DOUCLEFF: Then finally, his wife got it. But during this entire time, Esparza himself never got sick and never even tested positive.
ESPARZA: I have no idea (laughter). But I guess I just got lucky.
MARTIN: What's the explanation?
DOUCLEFF: Well, what scientists are starting to realize is that maybe he got lucky in that he carries a gene that actually protects him from getting COVID.
MARTIN: OK. So this is a new information. There's a gene that can do that.
DOUCLEFF: Yeah, it's kind of starting to look like that. Esparza may be what some are calling a COVID superdodger. Scientists are just starting to figure out what protects some of them from the disease. But first, there's a really, really interesting history to virus superdodgers that I want to tell you about.
MARTIN: And I want to hear it. Tell me.
DOUCLEFF: OK. So it starts back in the early '90s with this guy, Nathaniel Landau. He was a young HIV researcher at Rockefeller University. He was just starting his career, but he was already on the verge of making a landmark breakthrough. The breakthrough had to do with what some might call an HIV superdodger. Scientists had just identified groups of people who are completely resistant to HIV.
NATHANIEL LANDAU: People who knew they had been multiply exposed to HIV, mainly through unprotected sex, yet clearly they were not infected. So the question was, were these people just lucky or did they really have something that was protecting them from infection?
DOUCLEFF: So scientists all over the world were trying to find the answer.
LANDAU: Yes, we were totally stressed out. There were many labs all racing. And we, of course, wanted to be the first.
DOUCLEFF: Landau and his lab were getting really close to answering the question. They had already discovered a huge clue. It had to do with how HIV infects cells. They discovered that the virus needs a little extra help getting inside the cell. It needs to bind with a very specific molecule on the surface of a human cell in order to enter and infect it. It's a receptor molecule called CCR5.
LANDAU: That was what they call a eureka moment. That was the moment where you could say, I found something that had never been seen before.
DOUCLEFF: Then just a few weeks later, they made the breakthrough they were looking for. They figured out why superdodgers were protected. These people didn't make HIV's helper, CCR5.
LANDAU: We were quite amazed.
DOUCLEFF: Landau and his colleagues found a defect or a mutation in the gene that encodes for CCR5. So these people couldn't make the molecule. And without this molecule, HIV couldn't enter and infect their cells.
LANDAU: The virus sticks to the cell, but it just stays stuck there. It's kind of like it's knocking at the door, but nobody's opening the door. The door is locked.
DOUCLEFF: So no matter how many times a person is exposed to HIV, they couldn't get infected. They're protected and protected for life.
LANDAU: So in the case of resistance to HIV, the story was very clear. You can put as much virus as you want onto those cells, and they will not get infected.
DOUCLEFF: The finding completely shifted the field of HIV. It suggested a way to cure the disease, which scientists are still working on today. But it did something else. It showed scientists that a person could be completely resistant to an infection, a true superdodger. Now, 25 years later, the race is on again with COVID-19. Labs all over the world are racing to understand why people like my friend Joe Esparza may have somehow managed to avoid COVID-19.
JILL HOLLENBACH: It's been challenging and interesting (laughter).
DOUCLEFF: That's Jill Hollenbach. She's an immunogeneticist at the University of California, San Francisco. She's one of the scientists looking for genes that protect people from COVID-19. And after two years of hunting, she and her team have now found something very close. Now, unlike the HIV gene, this mutation doesn't stop an infection, but rather, it increases a person's chances of being completely asymptomatic if they do catch COVID.
HOLLENBACH: Not even a sniffle, not a scratchy throat, entirely asymptomatic.
DOUCLEFF: The gene is called HLA, and this particular mutation on it protects people from getting sick because it helps to clear out the virus very quickly.
HOLLENBACH: That immune response gets just kind of fired up much more quickly so that you basically nuke the infection before you even start to have symptoms.
DOUCLEFF: People with this mutation were armed and ready to fight SARS-CoV-2 even before vaccines came along. They were pre-armed, so to speak.
MARTIN: That is amazing. The people we joke about as having these superpowers, they actually did. They could have this gene that would explain why they never got it.
DOUCLEFF: What's even cooler is that Hollenbach and her team have found that perhaps 10% of people out there have this protective mutation. And for those who tested positive for COVID but were completely asymptomatic, that percentage is likely even higher. So, Rachel, this is not rare.
MARTIN: So interesting. But with this mutation, people still get infected with COVID, right? Have scientists found anything that completely stops COVID from entering a cell like the HIV mutation that you were talking about?
DOUCLEFF: Not yet. No, they haven't. And actually, it might be really hard to find this. Other than HIV, scientists have found only one more example of people who are totally resistant to a viral infection. Specifically, they found people who are completely resistant to a strain of norovirus, which is the vomit bug.
MARTIN: Oh, yeah, I know it.
DOUCLEFF: Yeah. But really, that's it. Nevertheless, though, several research groups are still searching for a true COVID-resistant gene, and they are actively looking for COVID superdodgers to participate in their study.
MARTIN: OK. So how do you become someone who qualifies for the experiment?
DOUCLEFF: Yeah. So if you think you've been exposed many times to COVID but never tested positive - and true exposure is like you're living with somebody who's sick - you can send an email to the researchers running the experiment. And if you qualify, the team sends you a little kit to collect some of your saliva. You mail it back in, and they sequence your entire genome. And we actually have a link to that email that you need online at npr.org.
MARTIN: Such a fascinating story. NPR's Michaeleen Doucleff, thank you so much.
DOUCLEFF: Thank you so much, Rachel.
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