Instant Genius - COVID in waste, with Dave O’Connor and Marc Johnson

Episode Date: October 27, 2022

In this episode Jason speaks to virologists Dave O’Connor and Marc Johnson from the University of Wisconsin–Madison.   For the past year they have been hunting down a heavily mutated strain of SARS-CoV-2, the virus that causes COVID-19 in a search that has led them to scour through everything from sewage water to dog poo.   In this episode they explain how viruses mutate, how there may be rogue forms of coronavirus still out there and how we can track viruses down. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Hello and welcome to Instant Genius, a bite-sized master class in podcast form. Each week you'll hear world-leading scientists and experts talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor at BBC Science Focus magazine. In this episode, I speak to virologists Dave O'Connor and Mark Johnson from the University of Wisconsin-Madison. For the past year, they've been hunting down a heavily mutated strain of SARS-COV-2. the virus that causes COVID-19, in a search that has led them to scour through everything from sewage water to dog poo. In this episode, they explain how viruses mutate,

how there may be rogue forms of coronavirus still in the wild, and how we can track viruses down. Okay, so first of all, we don't usually have two guests on this podcast. So I think first things first, I think if you could introduce yourselves, please just tell us a little bit about what you do and what your name is and your role is, etc. So I'm Mark Johnson. I am a virologist at the University of Missouri. I've been studying viruses my whole career. But when COVID kicked off, I got sucked into the world of wastewater surveillance because the poop was just too tantalizing. And yeah, so I found some weird things which led

me to meet Dave O'Connor here. And hi, thanks for having me. I'm Dave O'Connor. I'm a professor at the University of Wisconsin-Madison. So sort of up north in the U.S. near the Canadian border. And I've been studying viruses for about 25 years and also began working on COVID in Wisconsin when the virus arrived in 2020. Yeah, so we saw your research in, on a paper that you put out,

we thought it was really interesting. So you've been tracking a heavily mutated variant of the SARS COV2 virus in wastewater. So can you just tell me a little bit how this project got started? The original beginning was last March when we had first started measuring COVID from wastewater. We would sequence a small part of the genome. It's just every one of the variants has a little signature.

You could just say, oh, here are those two mutations. That's alpha or the UK variants as it was known at the time. But early on, there was this one sewer shed that started to have these combinations of mutations, this constellation of changes that didn't match anything. It wasn't any of the known variants. and it sort of drove me crazy trying to figure out what it was or where it was coming from. And we started working with lots of other groups, and I found that these were fairly rare, but not that rare.

And totally found a total of 24 out of probably more than 600 sewer shots we've tested. But when Omicron hit, we found a way of specifically saying, are there any weird winniages that are not Omicron? because once Omicron took over, it was the only thing we would find in wastewater. So we would have this probe that would say, is there anything other than Omicron that's in the sewer shed? And I reached out to groups all around the country and the world. And one of them was from Wisconsin where right out of the starting gates, one of their sewer sheds had this really interesting sample. It was like Omercron all over again, but it was some totally different changes.

And at the moment I got the results, I emailed Dave and Martin, who were my collect. in Wisconsin, like, oh my God, you've got one. And it's a juicy one, too. So we're talking about variants of the virus. So I think we should first sort of drill down into that a little bit. So how do the viruses mutate, you know, how frequent is that and how common is that? So that's a great question. And basically, the viruses typically don't change very much. If you were to infect Mark, the virus that Mark would get is going to look nearly identical to yours. And if you clear it out in a week or two, then the virus doesn't have much of an opportunity to accumulate change. This is why we think that a lot of the variants of concern, the variants that have emerged

over the last couple of years, come from these unusual infections, unusual either because they're unusually long in a person, because they are incubating in an animal, or the possibility that we're now considering based on this wastewater data, which is that in some small fraction of people, the virus establishes a sanctuary in the gut where it continues to produce virus for a long time, giving it an opportunity to generate new variants that some small number of people end up pooing out. So obviously a big part of this project is tracking the various variants of the virus. So how do we, how do you actually, what's the day to day in doing that? How do you track these viruses? Well, there are a lot of ways. I mean, so there are

tons of patient sequencing databases where people will submit the sequences and they're on a get on a database. And that's how actually most of the health organizations rely on those. But a lot of places have also started doing sewer shed tracking where you can measure from community, community, what are the dominant lineages? It doesn't tell you on an individual level, but you can tell you on a big picture level, oh, you know, BA7 just moved in or whatever, or BQ11 is the one that actually we're starting to see move in now. And you can actually follow what moving across the state even. It's pretty cool.

And it's usually several weeks ahead of the patient information. So the viruses get into the waste water just simply by being passed through the human body with bodily fluids. Well, there's some of that. And a lot of it's also that there do seem to be frequent secondary infections in the gut. But we think most of the time those get cleared along with the rest of the body. but it seems that probably some portion of the time that's not the case. And we still don't understand why, what do these patients have in common that have these really long-term infections, but that they do occur.

So what's sort of so special about the, you know, you said it's a juicy one. What's so special about it? So we start off by sequencing was called the receptor binding domain. This is the place where most of the antibodies that you want, the neutralizing antibodies where they bind, And so the virus realizes, oh, that's where it's binding, so we'll pick up mutations there, and then the antibodies don't work anymore. So they find a lot of mutations, but they're highly concentrated in this receptor binding domain. And most of the mutations are known to cause resistance to antibodies, ones that humans have already produced.

So, I mean, you could tell these aren't random mutations. That was very clear from the beginning. It's like, oh, my, this guy has been running from someone's immune system for some period of So I understand you track this to a very small area. Is that correct? Yeah. So when Mark first emailed me and Martin, our colleague, and said that he had found one of these in Wisconsin, I believe what his words were that he wanted to capture it and mounted above his fireplace because he wanted to figure out where this was coming from. Because we didn't know. We didn't know if it was coming from a person. Up here where I live, it's a very, I live in a sense. I live in a sense.

city of about 300,000 people, but it's surrounded by farmland. I have deer across the street from my house, and deer are known to be a reservoir. There's mice, there's other animals that could be carrying virus. For a while, we thought perhaps it was an agricultural phenomenon where it would be like a rendering facility where people would be bringing animal carcasses. At one point, we went and sampled a dog park thinking that people were fleshing dog poo down their toilets. And we really didn't know. And so what we would do is bring together a big team of people involved in the sanitation work, involved in public health, involved in research, involved in wastewater.

And basically we did detective work like something out of, you know, CSI, where we had a big board with a map of the sewer system. And we started with what we knew, which was that there was this virus in a sewer system. shed that served 100,000 people. Then within that, there were sort of branch points like on the tube where you could basically follow it down first to sub-treatment plants and then to individual manholes. And so we basically stopped at every individual manhole and asked whether the virus was still present there. And when it was, we kept going. And when we would hit a branch point, we would take both branch points and see where the virus was. And we eventually,

eventually worked out that the virus was in one manhole, but not another. And at that point, we said, okay, so we know that this is the end of the line for the virus. What is that serving? And it turns out that that one manhole served a single facility that had about 30 people who frequent it on a daily basis. There was nothing remarkable about the facility. We had thought we were going to trace this down to a hospital or to an aged care facility or to some other type of facility. Or a dog shelter. A dog shelter. Or a rat hive is what I thought. Yeah, and it wasn't. It was a totally unremarkable. It wasn't a supermarket, but imagine you just found it in a supermarket. That was about where we found it. And because that facility, it was only one facility, turned out to be a really great

partner. They allowed the sanitation department in public health to go inside the building and actually collect the sewage from within the building before it even gets to the manhole. And the signal was still there. And then there were two different outlets that gave rise to the facilities, wastewater, one from six bathrooms and one from another set of bathrooms. And only one of those two was positive. So we got it down to these six bathrooms within this one facility that are used by a small number of people that were giving rise to this virus.

And I just say there were two things that made this discovery so huge for me. The first is that when, and Dave will remember this, when I started working with Wisconsin, I was convinced this was probably coming from a rat. The lineage is frequently picked up particular mutations that had never been seen in patients, but are always seen when you make a rodent adaptive virus. So I'm like, it's got to be rats. And most of the places I'd seen them before were in New York City, where they did have a significant rat population.

So once we had narrowed it down and we knew that it couldn't be coming from a rat, there were no rats in the facility. There were no white-tailed deer using the toilets. It was coming from a person. But the second thing was, holy crap, how much virus was coming through this line. It was exponentially, I mean, 10 to 100 times higher than anything I had ever seen before. It was so, I mean, I don't know how many times do you flush in a 24-hour period, but it's maybe a thousand liters worth. diluted in a thousand liters that was this person's feces, you could take two drops of that, and it was enough to turn one of those rapid antigen tests positive. There was so much virus being shed.

It explained everything because what it never made sense is how this much material could be coming from a single person that we could detect it in a sewer shed. In at least in one case, it was 100 million gallons a day. I mean, my assay is good, but I mean, seriously, that's crazy. But once we saw the numbers, I'm like, I could dilute this a million fold and I would still be able to sequence this. It's like, okay, this is coming from single patients. It was incredible. It was, it totally changed the thinking about these. So was this person walking around with this virus inside them without even realizing? Presumably that is the case. You know, this is a, this is not a home. This is someone that is going to work every day.

and using the facilities while they're there. So, I mean, can this strain of the virus infect other people? We don't know. We don't think so. We think that the level of public concerns should be vanishingly low to non-existent. You're much more likely to be infected, going to a grocery store, going to a restaurant or a bar, being in public with any of the viruses that are out there right now that we know pose a threat than any amount of worry that we should have about these,

what we are calling these cryptic lineages. So a lot of work needs to be done in characterizing them because they are so unusual and enigmatic, but there's no reason for alarm. We just think that this is going to help provide a lot of visibility into different ways that the virus can persist, can evolve, and give us a crystal ball into where the virus might go in the future. But it's not something that people should worry about. I would say it's not an imminent threat. We can't even culturally the virus. We've tried from the waste. It seems to be inactive. It seems to be well contained, but I think we would all sleep better if this person were able to clear this virus and any threat were gone. Because who knows, some freak thing could happen. But it's very, it doesn't seem to be

happening. None of the cryptic lineages we've seen have shown any sign of spreading within the population. So you've found other similar, as you're calling them, cryptic lineages? We will find, you know, basically I could give you a list of 40 mutations, and we have found some combination of those in all 24 of the crypticlinages. They're never exactly the same, but they'll have the same combinations, and some mutations are favored more than others. So, you know, Omicron arrived last, last, whatever, November. Every one of the mutations in Omicron we had seen in our bag, and so there's some that are favored more than others, but it's always a combination the same ones. And that's where he's a really useful, because it can tell us

where Omicron and other variants will likely go next. So having said that, what is next for the project? What are you working on now and what do you want to be working on in the future? Sure. So we're really working closely with public health as well as with ethicists to figure out how far we can take this anonymous type of sampling of wastewater to figure out the source. And so we're hoping that we're going to be able to ask those who work in the

facility to voluntarily provide feces, and we're going to give them a choice. Do they want to know if we find anything that suggests that they're the source? And if they do, then we'll help connect them with medical care. If they don't, that's their choice. And then on a bigger picture, this type of wastewater sampling is extremely valuable when people are testing less. They're not getting as many PCR tests. They're not doing as many rats. We know we're missing lots of lots of cases. And by looking in wastewater, you get a composite picture of everything that's happening within a particular community. And so we're hoping that that will expand and will become a sort of permanent fixture in our surveillance because one of the silver linings in COVID

is that we not only can pick up COVID in wastewater, we can also pick up influenza. We can pick up other viruses. So by having a network that allows us to look for these viruses, we'll have a better idea of when and where they're in our communities. And then in addition to wastewater, we're doing a very similar type of project with air sampling. So trying to figure out within indoor spaces what sort of viruses are spreading in a school or in an airport or in a nursing home. both of those concepts center on the idea that testing individual people is something you're never ever going to be able to do enough of to know for certain what viruses are spreading. But if we do this kind of environmental testing, we'll be able to get that kind of information.

And on top of that, as we follow all of these cryptic lineages, which are basically all, you know, SARS-CoB-2s that have hit the fast forward button, we can start looking for commonality. and see, well, what's likely to happen with this virus in the next five years? Where is it likely to be changing? And how? Well, the only thing that I'll say, and I think it's important to say this, is that the wastewater work is interesting. But the thing that's imminent right now is the winter wave.

You're going to have it in the UK. Your listeners around the world are going to likely have a wave in the northern hemisphere winter. if they haven't gotten vaccinated and haven't been boosted, now is the time because here in the U.S., only about 5% of people who are eligible for updated boosters have received them to date. And that's a huge missed opportunity. So in terms of what you can do to protect yourself from COVID, getting boosted is an easy, inexpensive way of making it so that you're less likely to get really sick if you get infected. And that's the take-home message that anyone who does COVID work needs to try to drill home in as many different ways as possible. Thank you for listening to this episode of Instant Genius. That was virologists Dave O'Connor and Mark Johnson. The current issue of BBC Science Focus magazine is out now.

Pick up a copy wherever you buy your favorite magazines or visit ScienceFocus.com. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist vocal, Name creates high-end audio systems combining innovation with craftsmanship, so you can listen to music, just as the artist intended. Discover more at name audio.com.

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