How to track a Covid variant

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Jordan Heath-Rawlings I really wish that I wasn’t doing this today, but oh well, looks like it’s that time again. The Chief Medical Officer of Health tells me he’s worried about what he’s seeing with the virus right now and the impact it’s going to have and is having on Ontario hospitals. Seeing this trend early in October of increase in hospitalization, increase in intensive care unit, and watching newer strains in Europe has got me concerned. We’re going to spare you yet another episode about the untold strain our health care system is under and the public health measures that likely will not be coming back unless things get even more dire. If you’re listening to this program, you know that already. Instead, we’ll dig deeper on these concerning new variants, or rather sub variants. Where did they come from? What might they do to us? And how exactly do scientists across Canada and around the world chase these things, find them, label them, test them and track them when there could be dozens emerging at any time? How does a variant become the type of variant that concerns people like Ontario’s top doctor? Who rings that alarm bell? What has to happen before they do that? And what might we expect for this winter? I’m Jordan Heath-Rawlings. This is The Big Story. Dr. Sarah Otto is an evolutionary biologist, a professor at the University of British Columbia’s Department of Zoology and an expert with the coronavirus variants rapid response network. She goes by Sally. Hello, Sally.

Sally Otto Hello.

Jordan I’m not asking you to predict anything off the top. I know that’s not your gig and you don’t do that. But just based on the work you’re seeing with variants right now and what you’re hearing from colleagues, how’s this winter looking in terms of COVID.

Sally Otto Yeah, so this virus continues to evolve and with as many infections as we have globally, there’s actually a lot of evolutionary change going on. And so we’re actually in a very different phase of this viruses evolution than we’ve been in before. Really, it was about transmission. And we’d see these variants like alpha and then delta gamma that really were better at getting from person to person. And infecting people with these variants, it’s interesting, we’re seeing variants that are really evading or hiding the outside part of the virus and making it easier for them to infect people that have already been infected. You might go, well, what’s changed? And actually what’s changed is us, that at this point in Canada, almost 100% of us have been exposed to the virus, at least the spike protein of the virus, either through infection or through vaccination. And so the virus is now in a completely different kind of evolutionary regime where it’s really about getting around our immune systems and infecting us when we talk about variants that emerge. And I mean, you didn’t hear it, but in our intro I played a clip of Ontario’s top doctor, Dr. Moore, talking about variants coming from Europe.

Jordan How accurate is it that we try to put a place on where these variants come from? And what do we mean when we say, oh, it’s a variant from Europe or a variant from Africa? Really?

Sally Otto At this point, we’re seeing the same kinds of mutational changes, these kind of masquerading changes on the tip of the virus spike protein and they’re occurring all over the world. And so it is true that some of them start establishing in one place first. So we see recombinant variant XB and it’s spreading mainly in Asia, and we see things like BQ one mainly spreading in Europe. And that’s helpful for us because it gives us a little bit of a heads up about these variants spreading. But at this point, we’re seeing really, really similar mutations and a whole bunch of variants that are arising around the world. So I’m not sure that we should think about it as, oh, the risk is Europe.

Jordan When you say there are several variants around the world, how many variants are out there? And of those, because I understand this is a distinction, how many of them are worth people like you and your colleagues keeping an eye on and watching that’s, right?

Sally Otto So evolution happens all the time, mutations happen all the time. We know for this virus that it changes somewhere in its genome every two weeks. Most of those mutations are irrelevant or probably even hurt the virus. The ones we’re paying a lot more attention to are the ones that actually change it in some important way. And the ones that are really occurring over and over and over again at the moment are the ones in this receptor. It’s called a receptor binding domain. And it’s called that because it attaches to our cells on the receptors of our cells called case two. And so if it changes in that place, then it’s able to kind of get around our immune system and infect our cells still. So those are the places that we’re looking for mutations and where we’re seeing the same kind of mutations pop up again and again and again. Why those, those are the ones that were best recognized by our immune system. So people have looked to see what are antibodies best able to recognize. They’ve kind of found the spots on this spike that they’re best able to recognize. And lo and behold, that’s where this virus is changing again and again. It’s not that the virus is directing mutations in this part of the protein, but what’s happening is mutations are happening just always at some low rate. But those ones that are able to have mutations that do have, are lucky and have mutations in these spots are spreading and they’re spreading faster than the ones that have the old receptor binding domain.

Jordan I want to talk about the actual work of tracking these seemingly infinite variations, but then drilling down on the ones that could really do some damage to us. Maybe just start with the group you work with. What is the Coronavirus variants rapid response network? And how did it all come together?

Sally Otto A group of scientists from across Canada got together and recognized that to learn about and fight and develop the science that we needed to develop for Sars-COV2, we needed to work together. And so the team is really quite broad. We have immunologists, we have experts on indigenous health and indigenous community. We have experts in modeling and computational and genomics and all sorts of different people coming together and contributing what we know. So I’ve found it extremely useful to share knowledge just across such a broad array of scientists. So I’m in the computational and modeling pillar, and in our pillar, we’re kind of like the genome detectives. We are looking and scanning the genome. It’s amazing how much information we have about this virus. Over 13 million sequences have been amassed at this point, and that’s a lot of data. But that data, you got to know what to ignore and what to pay attention to. And so that’s where the sleuthing comes in, where we have to say, okay, well, this particular mutation, we’ve seen it a number of times, and it hasn’t gone anywhere. But this is a new combination. And look, it used to be at a frequency of 1%, and this week it’s now at a frequency of 5%. And that’s not just true here in Canada, but it’s true in other places. So we’re looking for those repeated patterns of rises in frequency, and that’s a hallmark of selection, evolutionary change that is driven by a selective advantage. And then we try and dig in further and say what might be going on? Is it because of an ability to evade our immune system? Or maybe it just gets into ourselves better? What’s going on? So you’ll start by looking at the numbers of infections and transmissions, and then if they show you that something might be up, that’s when you will look at the genome. I guess if that’s the right term for the virus itself. The genome is actually where our team is looking first. Because we can’t tell just from the number of cases which particular virus is infecting those particular individuals. And a lot of times what we’ve seen is the variant rising in frequency among the genomes, right? So we’re looking at the genomes, and we’re seeing something starting to rise, but cases are falling. And that happened in the BA to wave. In the BA5 wave, we’re seeing BA2 rise, but the number of cases are falling. And that’s because we’ve got this new variant on the horizon. It’s about to cause a new wave, but it’s not yet at the high enough numbers for us to see that impact. And so the genomes help us kind of get a preview of what’s spreading and what’s going to be driving the next wave.

Jordan When you identify one of these that you think might have a mutation that could make it something of note or something worth concern, what do you do? I’m exaggerating. But is there a bell that you ring? Is there a phone you pick up to call somebody? What happens?

Sally Otto Yeah. And I should say this is a global effort. And so when somebody is seeing again, not just something rising in frequency in one place, because that could just be a party happened, right. A super spreader event. And that’s what caused that particular virus to rise. And you’re looking for repeated evidence across time and across space. And it’s really interesting because Twitter has been a major place where scientists are sharing this kind of like, hot off the presses, watch out for this variant. There’s a lot of heads up going on there. And then there’s been a kind of difference in how we even do science. A lot more preprints and a lot more kind of posts. There’s a site called Veralogical and people post almost like a blog, and that allows that science to be shared really early.

Jordan As we speak now, end of October, early November, we’ve dropped basically all public health measures across Canada. So has the United States, so many other countries around the world. What is that doing to the number or severity of variants that are appearing on your radar?

Sally Otto So I should give an overall picture. And it’s important to emphasize that all of the variants that we’re seeing so far, these ones that are evading, immunity, better and better, they’re all Omicron variants. And that’s actually good news in that prior to Omicron, the COVID was a deep lung infection that could lead to really severe oxygen crises and intubation needs. Omicron broadly gets into our cells in a different way, and the cells that it gets into are more in our upper airways, so it evolves kind of a different type of disease…it’s more in our upper air pathogens. We think that’s how it transmits better from person to person because the virus is closer to where we breathe out. And that also has reduced the severity of this disease a little bit. That, coupled with vaccinations protecting us a little bit from the most severe outcomes, has given us a bit of buffer. And the hospitalization rates now with vaccinations and our immunity have reduced the number of infections per case. But I should be clear there that we’ve got fewer infections per case, but we’ve got more cases than we ever have, right? And so you multiply. You know, the good news is you’re less likely to land in hospital if you get infected. The bad news is you’re much, much more likely to get infected at the moment. And without masks, without really any public safety measures, we’re seeing kind of round after round of people getting infected. And we’re not even really tracking that here in British Columbia. We estimated, and it was confirmed by the BCCDC that approximately 100 times more people were getting infected than we know about in our official case counts. And that was a couple of months ago, so it might even be more than that now. And we don’t even count reinfections in that number or in the official case counts here in British Columbia. So we don’t know are people getting Omicron for the second, third or fourth time now in 2022?

Jordan So I think what does that mean? What does it mean if we’re getting so many infections?

Sally Otto Well, first of all, we’re still seeing really high hospitalization rates. So we’ve been seeing hospitalization rates that have been higher than any of the two previous years in the pandemic. And that’s just because of those high case loads continuing to see ongoing deaths and long covered cases that are a real risk factor even for younger people. And so those high infection rates are causing a massive impact on health care businesses because so many employees are homesick, as well as individuals who struggle long term with the kind of brain fog or lingering symptoms where they have trouble breathing or problems thinking or what have you. I want to ask a couple of practical questions about this fall and winter. You mentioned that reinfections are something we’re seeing a lot of. I had understood previously that when Omicron came around that obviously you could still get that if you’d had delta, or you could still get Delta if you’ve had Alpha. Does that change at all with these new variants being sub variants of Omicron? Do you have more immunity because you at least have had somewhat of the same strain? Or has it evolved to the point where that just doesn’t matter? Well, you know, the other thing about Omicron being so different in the first place is that our immunity to it has never been all that strong. That’s why scientists talk about waning. Our protection wanes faster with Omicron than it did with Delta or any other previous variants. And what that means is you can get infected, and then a few months later you can get infected again. And now that there’s really strong selection pressure for this virus to change on the outside, where it sees our immune system, that receptor binding domain, then we’re seeing it get in and infecting us again and again. So, yeah, reinfections are definitely here. And maybe one way to think about it is that we’re going to see some people talk about, well, the winter is really bad because of the flu season, but you kinda have one flu season. And I think what we’re in for is kind of recurrent high levels of COVID impulses when our immunity wanes and there’s more people that are susceptible to it. But I think for the next year, that’s what we’re going to be seeing. What do we know?

Jordan And you mentioned a couple specifically off the top about the variance that you’re concerned about this fall. You mentioned that they have a different way of evading the immune system. Are they still getting less severe? I think if you ask the average person, that would kind of be their understanding, right, is that this thing mutates, and it mutates to stay alive, but every time it does, it kind of gets less severe.

Sally Otto Yeah. First of all, evolutionary biologists does not predict that SARS Cove Two will evolve to be less severe. There’s a view that diseases do that because they evolved to let their hosts walk around more often. But the truth for Sars2 is that most of the really bad stuff happens after the virus has come and gone. So you have this major viral load in the first few weeks, but deaths tend to happen a lot later than that. And so it’s an unusual disease where really the virus is about getting out of your body and into somebody else, and that’s about transmission. It’s about evading the immune system. It’s not strongly selected at all to lower the severity, lower the risk of death. And in fact, we’ve seen variants, including delta as well as beta, that were more severe. It’s evolved to be more severe in the past. And with Omicron, we’ve been lucky and has evolved to be less severe. But while Omicron’s lucky in that sense, it’s about half as severe, half as likely a risk of hospitalization, all else being equal is also better at getting around our immune system. So it kind of undoes that benefit by just infecting more people.

Jordan What will you be looking for this fall and maybe on alert for, like, as I’ve mentioned to you, you’ve seen a ton of these things. A lot of them come and go. What keeps you up at night?

Sally Otto You know, actually, I’m looking a little better now than I was a couple of weeks ago. Okay, so let me tell you about these new variants in the horizon. As I said, we’re in a new regime where there’s really strong selection pressure for the virus to get into people that have immunity, at least a good amount of immunity. And so we’re seeing these mutations, you know, they’re called things like R, three, four, six, T. That’s not a very nice name, is it? What that means is that it’s at the 346 amino acid in the spike protein, and it changes it from an Arginine to a T, three Anine. So we’re paying attention to where these mutations are, and that’s one of the ones that kind of helps it masquerade. It looks a little bit different. Our bodies are less able to detect it and stop that virus from getting into our cells. So we’re seeing the same five mutations with names like three R, three four six, T. We’re seeing K four, four X, l four five, two X other ones like those mutations. And scientists were looking in the lab and saying, uh oh. These new variants, the one that’s most common in Canada is called BQ one one, has five of these kind of masquerading mutations. And in the lab, when they studied these variants, it all was finding, uh oh. If we sample our blood of individuals who have been vaccinated, who have had infections, what have you, it’s not really able to recognize and neutralize BQ one one. So that was really worrisome that it was so well masqueraded that maybe nobody would have immunity. And we’d have a whole ‘nother huge wave of BQ one one like we did at the beginning of the year with BA1, the first on the prong wave. But we’re not seeing that in Europe. They are now well into their BQ1 wave. It’s at about 50% frequency there. And we’re starting to see cases decline and hospitalization rates decline. And that’s great news because we just were unsure. Scientists around the world were unsure if this is going to rip roar through everybody, or is our immunity robust enough? Even though this neutralizing capacity is much lower, is it still going to be able to recognize other parts of the spike protein or clear cells that are infected so quickly that the virus is still stopped in its tracks? And I think the good news is we’re not seeing it rip or through Europe, and so we’re not likely to see it rip or through Canada.

Sally Otto Well, that’s good. We got enough on our hands right now. We have enough on hand. And just so you know, the latest where are we now? Would be to do that one dot one. I was just looking at it this morning, and there is about 5% frequency at the moment here in Canada. And definitely it’s growing. But again so I think that means in the next few weeks, we’re going to see a rise in cases, a rise in spread. But hopefully, like in Europe, this won’t be a very long lasting wave, and we’ll see case numbers come back down again soon.

Jordan Fingers crossed. Thank you very much.

Sally Otto You’re welcome. Dr. Sarah Otto of the University of British Columbia. That was The Big Story. We are queuing up some brand new outro music for you today. You asked us to switch up things and make the end of this program less repetitive. This is part of our ongoing effort to do that. I also have one quick piece of feedback, I promise. I usually will not repeat just complimentary pieces, but in this case, it was a very nice email from a listener named Rob. One of the things he mentioned is that he appreciated how I approached Arnold Kopecky’s analysis with I don’t know much about BC politics. I did that because I don’t. Now he says, Jordan is clearly aware of the Dunning Krueger effect, and I wish more talking heads were. My initial reaction to that was to pretend I knew exactly what the Dunning Kruger’s effect was. I didn’t. I had to google it. Which actually proves Rob’s point. So. Thank you, Rob. Yes, we all know that I’m an idiot. You can find the big story at thebigstorypodcast CA. You can find us on Twitter at thebigstory FPN. You can also talk to us anytime via voicemail. We won’t talk back because we don’t answer the phone. 416-935-5935. And you can find this podcast wherever you get them. You can look it up in Castbox overcast podcast and radio addict Echo podcasts. That is a new one on me, but it makes up a full 1% of our listeners, so I will try it out. Thanks for listening. I’m Jordan Heath-Rawlings. Stay safe as we head into winter. We’ll talk tomorrow.