What Scientists Got Wrong About COVID-19

Early in the beginning of the COVID-19 pandemic, scientists predicted the SARS-CoV-2 virus would mutate slowly https://www.npr.org/2020/03/26/822107691/the-coronavirus-is-mutating-relatively-slowly-which-may-be-good-news. They were wrong. Hundreds of thousands of viral mutations https://www.sciencedirect.com/science/article/pii/S2665928X23000132?via%3Dihub and multiple seasonal waves https://www.npr.org/2024/08/15/nx-s1-5075060/covid-summer-wave-variants-vaccine later, we now know why. The answer changes researchers' understanding of viral evolution — and it could help predict the evolution of other viruses in the future. Emily https://www.npr.org/people/767284140/emily-kwong talks about it all with Sarah Zhang https://www.theatlantic.com/author/sarah-zhang/, a health writer for The Atlantic. Want to hear more virology or human biology stories? Let us know by emailing [email protected] mailto:[email protected]. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:22Emily Kwong?

  Hey, Short Wavers. Emily Kwong here. So this month marks five years since officials at the World Health Organization declared COVID-19 a pandemic, and we have come a long way since then. Researchers have figured out ways to slow the spread of the SARS-CoV-2 virus with masking and air filtering. They've developed safe treatments and vaccines, and they've tracked hundreds of thousands of different mutations. And now we know something else: how those mutations evolved. Because if you remember, in March of 2020, a lot of scientists predicted that the coronavirus was not going to evolve very much.

• 0:58Speaker 02

  It was thought that the coronavirus mutated pretty slowly, like half as fast as the flu or only a quarter as fast as HIV.

• 1:06Emily Kwong?

  This is Sarah Zhang, a health writer for The Atlantic. Back in 2020, some scientists thought that once vaccines arrived, they would offer years of protection.

• 1:14Speaker 02

  Unfortunately, I think we know what actually happened, which is that in the winter of 2020, we sort of got like this first big variant, what was known as Alpha. And then we just kept getting more and more variants.

• 1:27Emily Kwong?

  Beta, Delta, Omicron. The coronavirus continued to mutate to make these evolutionary jumps that helped it survive. And for a long time, scientists didn't know why. Sarah wrote a piece about this for The Atlantic last month, focusing on a series of studies that point to a relatively new idea: that the virus could be incubating and mutating further in one specific group of people.

• 1:53Speaker 02

  When the virus jumps from person to person, it gets about two mutations a month. But sometimes, when the virus finds someone who maybe their immune system is a little bit suppressed, they aren't able to fight off the virus. Instead of, you know, being sick for like a week or two weeks, they might be sick for weeks or weeks on end, or even months.

• 2:10Emily Kwong?

  Meaning that in people who are immunocompromised, the virus may be able to stick around and evolve.

• 2:16Speaker 02

  And in this process, it's almost like a training camp for the virus to figure out how to evade the human immune system. The virus during a long, persistent infection might find just the right combination mutations that makes it really good at infecting lots and lots of people.

• 2:31Emily Kwong?

  So today on the show, rethinking the rules of viral evolution and how scientists are racing to catch up and predict COVID's next move. I'm Emily Kwong, and you're listening to Short Wave, the science podcast from NPR.

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• 4:14Emily Kwong?

  So just to take a big step back, Sarah, why do viruses mutate? And what does that do to us when we get infected?

• 4:22Speaker 02

  Yeah, so when a virus infects you, it's basically copying itself millions and billions of times over and over again, right?

• 4:28Emily Kwong?

  So it can spread?

• 4:29Speaker 02

  Yeah.

• 4:29Emily Kwong?

  To different cells?

• 4:30Speaker 02

  Right, because it infects one cell, then it makes thousands of copies of itself. And then now you have thousands of copies to infect thousands more cells. It's basically a numbers game. The more of yourself you can make, the more of your progeny out there can continue to infect more people to continue to have more progeny out there. Most of these mutations, they don't really do anything. But in a really small number of cases, that mutation, or maybe even the whole set of mutations, might give the virus some advantage. Maybe it makes it better at entering cells. Or maybe it makes it better at infecting the upper airway so you can cough it up and then infect someone else.

• 5:06Emily Kwong?

  OK, so there's almost like one star pupil, or a few star pupils, who will prove advantageous against the army of the human immune system.

• 5:15Speaker 02

  Exactly. The star pupil is going to be one that just has a slight edge. It's a little bit better at copying itself. It's going to keep doing it more and more and more.

• 5:22Emily Kwong?

  And it has. It has continued to evolve. But right now, most of the variants that are dominant in the US are descendants of Omicron. Tell us about Omicron's origin story. When did it appear as a variant? And what surprised scientists about it immediately?

• 5:36Speaker 02

  Yeah, I sort of remember it happening, I think, just before Thanksgiving in 2021. And I think at that point, vaccines were pretty available. Things were maybe starting to settle back to normal. And then scientists made this big announcement that was really stunning, if you knew anything about viral evolution. And I think it was scientists in South Africa who first noticed it. They said, "We have this new variant that we found. It has 50 mutations."

• 6:02Emily Kwong?

  Whoa.

• 6:03Speaker 02

  Thirty of them.

• 6:03Emily Kwong?

  It racked up 50 mutations?

• 6:04Speaker 02

  Yeah, 50, five-zero mutations. Thirty of those mutations are all in the spike protein. And the spike protein, if you remember, is kind of the key that viruses use to enter our cells. So it's really important. It's also what's in our vaccines. So it's how our immune system, once we've been vaccinated, recognizes a virus. If you think of a vaccine as giving your immune system a mugshot, lots of changes in the spike protein mean the virus is put on a hat and changes glasses and its clothes. So it's not as recognizable to your immune system.

• 6:37Emily Kwong?

  Omicron rolled up and was like, I'm gonna be something like you've never seen before.

• 6:41Speaker 02

  Yeah, exactly. And so clearly, this was gonna be a sign of trouble because our immune systems were not really good at recognizing Omicron. Like people, even people who had been vaccinated, even people who had gotten COVID, you know, pre-Omicron, their immune system had this outdated mugshot of what this virus now looked like. So it was pretty clear that we were probably gonna get reinfected, or even if you're vaccinated, you're probably gonna get infected.

• 7:09Emily Kwong?

  Yeah, I remember this period as the Omicron wave of 2021. And you write that scientists think Omicron's rapid evolution is something to do with the virus incubating and mutating in immunocompromised people. It's a super interesting idea. Can you explain why scientists suspect that?

• 7:28Speaker 02

  Yeah, so we don't like have, we haven't traced Omicron back to like one person, and I just want to be clear about that. There's been a lot of sort of indirect evidence that suggests like this is what happened. So, you know, I mentioned Omicron has 50 different mutations, but 30 of them are all in spike.

• 7:44Emily Kwong?

  Yeah.

• 7:44Speaker 02

  Over time, as scientists have been studying these persistent infections in immunocompromised people, they see this very clear pattern that you not only get a lot of mutations, but you get them concentrated in spike. And the reason is probably because, you know, as the virus is infecting someone for weeks or months at a time, the immune system, even as someone who's immunocompromised, so like can do a little bit, right? Not enough to entirely clear the virus, but maybe enough to like suppress it a little bit. And it's still like recognizing the virus. But if the virus is able to change its spike, then it gets a little bit harder. They're kind of in this like back and forth cat and mouse game. It's really about the length of infection. You know, just like basically the more time

• 8:26Speaker 02

  you have, the more even random mutations you can accumulate. And some of these mutations will, will probably give it some sort of edge. And in most cases, it's not enough of the edge for the virus to then spread from that initial person. But in really rare cases, like probably Omicron, it does.

• 8:46Emily Kwong?

  What kinds of immunocompromised patients are we talking about? Do they include folks with long COVID?

• 8:52Speaker 02

  Yeah, that's a really good question. You know, the researchers I talked to who study this are really clear that these persistent infections aren't necessarily the same thing as long COVID. With long COVID, it's not like necessary that you are shedding viruses the entire time you're sick. With someone with one of these persistent infections, like you are shedding virus. So it's not the same thing as long COVID. It's possible that some people who have long COVID actually have one of these persistent infections. But I don't want to say that. I want to be pretty clear that they're not thought of as the same thing.

• 9:25Emily Kwong?

  So when it comes to just the rapid mutation capability of SARS-CoV-2, is it simply that it's just more powerful than other viruses? It's just better somehow?

• 9:35Speaker 02

  That's such a good question, and I think really one of the open questions of what's going on here, right? It's definitely true. We have not seen this with any other virus. You know, is this dynamic something specific to SARS-CoV-2? Or is it just like when you have a new virus jumping into new species for the first time, it just has like so many opportunities to mutate that it's just had all these chances because it's new? Or is there something that is, gives it some sort of ability that other viruses don't? And I don't think we entirely know yet.

• 10:07Emily Kwong?

  This phenomenon where a virus mutates more in immunocompromised patients, can that happen with any virus like HIV or bird flu?

• 10:18Speaker 02

  Yeah, we haven't seen this exact pattern in other viruses, but a few years ago before COVID, one of the scientists I talked to had studied flu in patients who were immunocompromised and had the flu for weeks and weeks. And he did find that you could see some of the same mutations over weeks inside these immunocompromised patients as you would then see the seasonal flu next year.

• 10:42Emily Kwong?

  Wow, that's really interesting.

• 10:43Speaker 02

  Though the thing that's different is that he didn't find any evidence that the flu viruses from immunocompromised patients was actually seeding next year's seasonal flu, right? He just thought they were happening in parallel. With SARS-CoV-2, it seems like one actually is seeding the other. These persistent infections are seeding the viruses that then affect all of us over the next few years. So I think this is somewhat new. And that's why it was so surprising that this could happen.

• 11:12Emily Kwong?

  Yeah, but part of what's cool about COVID is it's been sequenced in such depth. Like, we've really been tracking its every move.

• 11:19Speaker 02

  Yeah, we've never sequenced any other virus to the extent that we sequence COVID. So there's probably, there's probably a lot of stuff going on in viral evolution that we are just entirely not aware of because we are not sequencing other viruses, right? There are like, at least dozens, maybe even hundreds of viruses that cause the common cold. We don't really have a great grasp of how they evolve from year to year, from year to year.

• 11:43Emily Kwong?

  Man, so COVID really is changing how virology is done. It could change our understanding of viruses. If, if this tracking were to especially focus on infections within those who are immunocompromised, what would that do to disease surveillance?

• 11:59Speaker 02

  Yeah, something really interesting is that when scientists, even back, like, back in 2020, were looking at how viruses change in persistent infections, they were seeing some of the same mutations that ended up showing up in these variants, months and even sometimes years later.

• 12:16Emily Kwong?

  Oh, so almost like a crystal ball?

• 12:18Speaker 02

  Yeah, exactly. What's happening inside one infection is physically like a sped-up version of what might happen out in the world. So, you know, there's some thought that like, hey, if we could just keep a closer eye on these persistent infections, maybe that will give us a sense of what the virus is going to look like, you know, a month from now, or maybe a year from now. And I think it's important to sort of keep an eye on these things to make sure we see them early enough that we can start to take action. But also, I think we have to keep an open mind and, you know, we might not know what's going to happen in the future.

• 12:55Emily Kwong?

  Well, in the meantime, you are following as closely as you can. Sarah Zhang, thank you so much for talking to me.

• 13:00Speaker 02

  Thank you for having me.

• 13:03Emily Kwong?

  This episode was produced by Hannah Chin and edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Robert Rodriguez was the audio engineer. Beth Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting strategy. I'm Emily Kwong. Thanks for listening to Short Wave, the science podcast from NPR.

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