Radiolab - Dispatch 14: Covid Crystal Ball

Episode Date: March 12, 2021

Last summer, at a hospital in England, a man in his 70s being treated for complications with cancer tested positive for covid-19. He had lymphoma, and the disease plus his drugs weakened his immune system, making him particularly susceptible to the virus. He wasn’t too bad off, considering, and was sent home. That was Day 1. This is the story of what the doctors witnessed, over the course of his illness: the evolution of covid-19 inside his body. Before their eyes, they get a hint of what might be to come in the pandemic.  This episode was reported by Molly Webster.  Special thanks to Ravindra Gupta, Jonathan Li. Support Radiolab by becoming a member today at Radiolab.org/donate.      Want to learn more about some of the covid case studies? Here are a couple papers to get you started:The “U.K. Paper”, co-authored by Ravi Gupta, one of our sources for the episode: https://www.nature.com/articles/s41586-021-03291-y A case study out of Boston, co-authored by Dr. Jonathan Li, one of our sources for the episode: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 For more on immune suppression and covid-19, check out this amazing Scientific American article:  https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/

Wait, you're listening to radio lab from W and Y Whoops, are you there? Yeah, that's it. That was amazing. You started coming. I still don't see you. I'm, Chad, I've been around. This is Radio Lab, dispatch number, whatever number we're at. I'm gonna say 14, I'm not sure.

This dispatch is a little bit more low five than even our others because, I don't know, I just wanted to play you a conversation I had with senior correspondent Molly Webster. She and I check in every Friday morning, where she usually just kind of updates me on new research. She's following things she's been interested in and in this case her research update to me last Friday was just so interesting. I'm recording. You're here. You're recording. That we decided to record. Okay we'll talk and then you

just tell me to stop whenever. I will tell you to stop it. Why would I tell you that? You know, Chad, you'd be the rare person in my life who doesn't. She told me about a few new studies that she had just read. These were articles about different individual COVID patients from different spots around the world and each paper looked at how the virus behaves inside a single human body one a case study from the UK starts with a man in his 70s Coming into a hospital with an immune system that was already pretty low

Yeah, his immune system was low because he had lymphoma Uh-huh, and then was on a drug to try and keep the cancer in check and that lowers your immune system. So this man in his 70s? He had a suppressed immune system and he shows up in a hospital because of cancer stuff and while he's there, they test him and he's positive for SARS-CoV-2. But he seems relatively fine and he just just has a small cough or something, and so they send him home.

And then, 35 or 34 days later on, day 35, he walks back into the hospital and what had been a cough for the last month had turned into a shortness of breath. And they test him again again and he has coronavirus. Which most likely meant that he had coronavirus for the whole month and couldn't get rid of it. So he tests positive for coronavirus and he has like the COVID-19 pneumonia kind of that settles into your lungs. The crackly cough thing. Yeah, you know, the gray spots on the lungs that they like identifying

CT scans and stuff. And so they check them into the hospital. And then what basically starts is just a series of trying to treat this man at the same time the UK is actually really good about taking samples and genetically sequencing them. As we all know in a way that America is not doing right now. And so over the course of his time in the hospital, and he does eventually end up dying on what they say is day 102. Oh, wow.

Over the course of that time, they sequenced his virus 23 times. So basically, over the last three and a half months of this man's life, the doctors take snapshots of the virus inside him. You can think of these as a series of stills that capture what the virus is doing, how it is moving. You can think of them as mug shots, series of mug shots. Now at this point, this is going back a year, there was really only one main version of SARS-CoV-2 that was out there, or at least in our consciousness.

There weren't all of these variants from South Africa or Brazil. Or the New York City variant. That there's a new one? Yeah, I did. And now the New York City one is new, and now there's a new Oregon variant. Oh snap.

None of that was on our radar, yeah, we were just focused on the original. The original, like what I call like OG SARS-CoV-2. That was the perp that the doctors expected to see on all those mug shots. And they did see it on day one. But then when he went away and came back 34-ish days later and proceeded to get sicker and sicker in the hospital. They sequenced again, and this time they saw something different.

Instead of just one COVID virus inside them. They saw pop-up, like, little subpopulations. They saw a whole bunch of different kinds. With enough variation that they look different. What they noticed is like, oh, there's still the dominant, like, OG SARS-CoV-2 genetic sequence all over this body. Okay. But there's like really small quiet,

like subpopulations that are hanging around. And at the time, they were like, whoa, whoa, whoa, there's all these like variations. Whoa, has this person been infected by like six different types of this virus? And they all happen to, has this person been infected by like six different types of this virus? And they all happen to get into this person at the same time? Oh, like he somehow managed to have six different encounters with six different coronaviruses or like they want to get a case and then it cleared. Yeah. And then

maybe got it again. And then again and again and again. So the doctors at that point have a new thought. Maybe this isn't the same infection that he's had the whole time. Maybe these are separate viruses, entirely separate. But, and they realize, no, this is one strain that got in and just keeps changing, changing, changing, changing, changing. In other words, what the researchers came to understand,

and they weren't trying to study this. They were simply trying to say the man's life, is that these subpopulations were one virus rapidly mutating, trying out new forms inside a human body. That when you have a human body that has a compromised immune system, the COVID virus will just rapidly experiment. That the immune-suppressed body is like a playground of sorts, because nothing actually shuts the virus down, and it can replicate un-inhibited. This one researcher said that at any point in time when you're infected with coronavirus,

you can have at least a billion copies of the virus inside of you. One billion? One billion. And so that means that every time it replicates, it has a chance to mutate, substitute, delete one little nucleotide. But I thought the whole deal with the coronavirus. I mean, you and I did a story about this. Is that unlike the other RNA viruses, which are super sloppy, the coronavirus actually catches its own mistakes pretty well and doesn't mutate that much.

So it doesn't actually mutate that fast, but it still does just mutate, and every time it replicates, there is a chance that mutation can set in in and hence evolution can happen, right? Because if you change part of your genetic code, you have a chance to like have new characteristics that let you survive in the world in a different way. And so if it's in the body and it's allowed to replicate a billion times with really nothing to stop it every time it replicates you throw the dice and something can happen. So getting back to this guy, the researchers noticed that he's got all of these different subpopulations of SARS-CoV-2 viruses, different kinds inside of them. But most of the new variants? They're not really doing much. They don't have much dominance. Like if

you actually look at the numbers, I think it's something like I may be making this up, but I don't think I am, but it's something like the original genetic virus is almost at a hundred percent dominance And every every other little subpopulation is like less than two percent But then she says the doctors start to give this guy treatments So he gets the hospital day 35, day 41, they do a round of REM desiveer. That's one of the few drug treatments available against the virus. Day 54, they do another round of REM desiveer.

And then on day 63, they give them convalescent plasma from a donor. And this is like the blood you take from the body of a person who has successfully fought off Covey 2. And you put it in a person who's struggling to mount an antibody defense system to like take the virus down. The thought is, and this is also a story we've done, the antibodies in the survivor's blood will help you fight off the virus. So day 6 to 3, guy gets infusion of plasma. And then on day 65, they give them another batch of convalescent plasma. So they're like giving treatments, and then as they're giving treatments, they're taking

samples and genetically sequencing them. And what they see is that by the time they check his samples in the 80s, like day 82 or day 81 The the different sub types have like exploded really And and there are like very noticeable changes in the coronavirus inside his body More on that, after the break. Hi, this is Deandra from the Long Beach Peninsula, Washington. Radio Lab was supported in part by the Alfred P. Sloan Foundation, enhancing public understanding of science and technology

in the modern world. More information about Sloan at www.Sloan.org Science reporting on Radio Lab is supported in part by Science Sandbox, a Simon's Foundation initiative dedicated to engaging everyone with the process of science. This is Radio Lab, I'm Chad Abemurad. Today we are in Molly Webster territory. Actually we are in the middle of a recording of Heronize Weekly Meeting where she was telling me about some papers that have just come out that show how the SARS-CoV-2 virus behaves inside a single human body.

I also just want to say before we rejoin that conversation, God bless the man in the UK. The human beings who are at the center of these case studies. Papers kept their identities secret. Of course, we will obviously do the same, but in a few of these cases, not all, these people passed away. the same, but in a few of these cases, not all, these people passed away. And they allowed doctors to study them in the final months of their life so that we could all learn something about the nature of this enemy, so endless gratitude to those people.

Okay, so before the break, Molly was explaining that in this man in the UK with a compromised immune system, the doctors first noticed that there were all of these variants of the coronavirus popping up, like all these different subpopulations, which were basically kept in check for a while, but then as soon as the doctors started trying to treat the patient with drugs and convalescent plasma, those subpopulations just explode. And there are like very noticeable changes in the coronavirus inside his body. They see like these deletions, that they call deletions at 69 and 70.

And then there's this other mutation at something called 796. It's very wonky like all based on like amino acid positioning. Okay. And suddenly that, that virus variant is like dominant. And the OG stars cove2 virus variant has like become a quiet subpopulation. Weird. So, okay, help me unpack what that. Yeah. I don't quite know how to, how to to hear that does that mean that that whatever that it was in the plasma whatever antibody army came in from the donor obliterated OG SARS But it somehow allowed for this little sub population to just bloom essentially so what they say is like oh my gosh we added in all of these antibodies, and we've just witnessed how SARS-CoV-2 might try

and get around those antibodies. So they basically witnessed evolution happening right in front of them? Yes. Is that the way to say it? That is right. And in the example you just gave where there was a mutation in 1690 or 70 or whatever it was,

what does that actually do for the virus? So the 6970 deletion on its own makes the virus twice as efficient at infecting cells. Really? And they think that's because it can clamp on more tightly to your cells. And so if you have that variation, you bind more tightly, which means like when you inject

your genetic material, it all gets inside. And like the cell can't shake you. Okay, so we're only at stage one here. So they see this scary mutation bloom in this one patient, this poor man. And then Molly says, as they kept trying to treat the man, and then test him to measure the effect of those treatments, they saw this kind of real time evolution, just continue and escalate. They'd see all of these different populations come and go, rise, fall.

There might be two different types, and they rise and fall together. And then there's somewhere like if virus variant A is in there, D won't survive. I have this like a little part of the paper cut out. I'm just going to read it to you. It's as patterns in the variant frequencies suggest competition between virus populations carrying different mutations. Viruses with the mutation deletion pair, spike, letter of 796, 6970, rose to high frequency during convalescent plasma therapy, but were then out competed

by another population in the absence of therapy. Specifically, these data are consistent with a lineage of viruses with the NSP2i513T and RDRP V157L variant, which was dominant on day 66 but was out competed during therapy by the mutation deletion variant, that's 796 and 6970, with the lapsed in therapy the original strain, which had acquired NSP 15N1773S and the spike Y200HT240i, regained dominance, followed by the emergence of a separate population with the spike W64 GP 330S variant. That's like one paragraph from the paper. I said, though, so those are all different subpopulations

of coronaviruses that are kind of duking it out in this one guy. This all happened in that one body, in that one patient in the UK, this is just from that paper. How many different corona tribes are we talking about? Let's just see if we can do a quick count. So, it's 501Y, 796, 6970, 240i, 200h, 330s, W64g, i513T, V157L, and 1773S. So something like at least 10 different populations,

rows and fell. Viruses have state, like these virus variants have exist in different parts of the body. Some of them exist all over globally. Some exist in different parts of the body. Some of them exist all over globally. Some exist in different parts of the body and they're all having different types of battles with the things that you're putting inside. And then they're all having different types of battles with each other. And they're seeing this in a single human. Yes, a single person. Wow, I don't know why, but this is completely

blind my mind. Well, because one of the scientists described it as like you can see a single body, a single patient as like a battleground or a training ground. Oh wow. That's scary. If you look, if you look in and follow, no, it's like if you can look in and Follow the action. It's almost like the Truman show, but rather than us being in the Truman show You're looking in you're looking into the Truman show like watching the world Change and be manipulated and you're like now I want to make it rain Now, now I will cause a tornado and I'm gonna see like how the world Now I will cause a tornado and I'm gonna see like how the world re that how this world reacts to that. It's just like a whole microcosm inside one person. And in that passage of red, it said that the different populations of coronavirus are competing.

Are they fighting? How are they fighting? Not fighting. It's all about real estate, really. It's like, can you get in a cell? How fast can you get in a cell and How fast can you get in a cell and how quickly can you replicate in that cell? If you think about the body, there is a limited number of cells for the virus to infect. And so if it wants to make lots of different types of itself, and I'm saying wants like it has like a wish, if it wants to make different types of itself, all of those different variants are fighting for the same real estate. Like there's one paper about a patient who had a immune suppressed, had coronavirus for at least 70 days, asymptomatic.

Eventually it cleared their system, but they saw the virus mutating inside this one person. There's something a medicine can witness. I think it's not even like learn. It's like actually like what we can witness is in a sense, everything that is happening out in the wild, but like in one place. Whoa, whoa, be, oh yeah, I just did a big jump. You just made a jump, which is, which is where my mind was going, which was, yeah. If, okay, so if we zoom out just a bit

and we look at this one body and we see that these variations, these different populations that are rising and falling and competing for real estate, is there anything that they are seeing in these single human cases inside of these single immunosuppressed people that is mirroring what we're seeing out in the world in terms of all the different variants that are floating around in South Africa and Brazil and all that? Africa and Brazil and all that. So that's where it gets really spinny. That's that's where it gets

really trippy is that these patients end up being like a blueprint. Like with them, you could see what the virus might do in the future. And to break that down, what they saw happen inside those bodies where the formation and creation of mutations that then appeared out in the wild six months later in like the UK variant, the South African variant, and the Brazil variant that we're all like running scared from. Whoa. Five months before a scary virus variant showed up in the wild, they saw it inside a person. Okay, okay, okay. If they're seeing these mutations dominate in immunocompromised bodies before they dominate

in the wild, does that tell them that they started an immunocompromised body and then got out into the wild? Well, so that's an interesting question. So with these specific case studies that were and then got out into the wild? Well, so that's an interesting question. So with these specific case studies that were written up, whatever happened inside the body never left the body, because the patient was in hospital the whole time and closed down. But the thought now is based on two of these case studies

and a few others that have come out is that probably at least the UK variant that B117 came out of an immunocompromised body because they said that variant has like eight significant mutations in it and in order to get that in the wild, it would take many many months. And if you were genetically sequencing like they do very frequently in the UK, you would see the tracings of that change start to happen. Interesting. Like, oh, there's a change here. That's change one. There's a change here. That's change two. There's a change here

That's change three. But everyone said one day they woke up and there was a new virus with eight significant changes. Which makes them think that that all happened in one hidden place and then burst onto the scene. That's so funny because that was the experience of consuming the news, was it like, oh, co-co-e-to, and then I remember hearing that it doesn't mutate that much, okay, great. Glad to hear that. And we'veate that much. Okay, great. Yeah.

Glad to hear that. And we've got these vaccines coming in. Yay. And then suddenly I like literally on a Tuesday, everyone was like, oh snap. There's a very. We've got a new variant. And I'm like, wait, what? Where did that come from?

Yeah, where did that come from? Well, scientists have the same reaction. And what they're saying is in these like immune suppressed patients where you can witness the virus trying to adapt and where you can like step-by-step see how it interacts with each treatment, you give it, you can actually have a clue to like, how the virus might change in the future. Because if, if, if, if, if, if, if, if, if, Because if bananas, that's so weird.

Like seeing the future. It is. It is. Like there's one guy called it a crystal ball. Another guy called it the a harbinger of like what's to come in the virus. Until like he I. That's so wild. Yeah, the idea is at some level the virus can change a lot of ways, but at another level, it can only change so many ways. And so if you watch it mutate, like, a million, two million, three million, four million,

five million times inside a person's body, and you see which variants dominate, there's like a pretty good chance that, like, okay, if the virus ever rolled the dice out in the wild and It landed on this mutation this mutation would take hold and thrive. So it's very possible It's gonna hit the same mutations in different places independently and we might be able to see that in advance inside one person. Yes Yeah, you know, it's what I Would I when I'm struck by. Yeah. It's really, it's, it's, it's interesting to hear the story right now. You know, because it's, it's, it's like from one moment to the next, it's really hard

to know whether to feel optimistic or pessimistic, right? Right. You know, it's like, and kind of the story you're telling, and it's weird to like look outside and see like, oh, it's sunny, like spring is coming. Like, the vaccines are rolling out. We might actually get to go have dinner with friends again, and everybody's like in this kind of like, ah, ah, normal life is returning. What the story you're telling me is like, is it? Virus is crafty.

Then maybe so are we? I don't know. It's weird to juxtapose what you're saying against that sense of like optimism that's out in the world because what I'm hearing is that simultaneously, this virus is figuring us out and we're figuring it out. And maybe we're turning the corner or maybe we're just in the first chapter

of a very long story, you know? Yeah, like I... I think I keep having a, having a lot of visuals. Like myself and I would say my community are probably at the lowest ed. I've seen them act in the last year. But also with, with a whole bunch of like hope. Just starting to like glimmer. I keep thinking of that midnight in the garden

of good and evil statue. Do you know what that is? It's like the little girl and she has her hands up by her shoulders with her palms like up to the sky. And it's like good and evil are like weighted on each side. I feel like that feels like this moment in COVID to me where you're holding like optimism and pessimism, you're holding like hope and just like utter exhaustion, like, I'm both shoulders.

Yeah. Wow. Yeah, that's exactly it. This episode would not be possible without the council and the interviews with Ravi Gupta and Jonathan Lee. Thank you both so, so much. Huge thanks to them and thanks again to Molly and to you for listening. I'm Chad Abel-Marrad. We'll be them and thanks again to Molly and to you for listening, I'm Chad Abel Mrod. We'll be back with you again next week.

Hi, my name is Sophia Berg, I'm calling from Bonn, Germany. Vailulet was created by Chad Abel Mrod and is edited by Thorin Wheeler. Lulu Miller and Lottesnasa are our co-host, Suzy Lecdenberg, our executive producer, Dylan Kease is our director of Sound Online. I'll start off with Putes, Simon Edler, Jeremy Bloom, Becca Bressler, Rachel Kusik, David Gable, Matt Kielty, Annie McEwan, Sarah Carrey, Ariane Wack, Pat Walters, and Molly Webster,

with help from Chima, Oliyae, Sarah Sandback, Johnny Moons and Karen Young. Our fact checkers are Diane Kelly and Emily Krieger. I'm you