Looking Ahead To Our Third Pandemic Winter

KATHLEEN DAVIS: This is Science Friday. I’m Kathleen Davis.

KATHERINE WU: And I’m Katherine Wu. Winter is approaching in the Northern hemisphere. More people will be indoors, traveling to attend holiday gatherings, and generally at higher risk of catching the coronavirus. Last year, winter also coincided with the emergence of the fast-spreading, antibody-dodging Omicron variant.

At its peak, more than 2,600 Americans were dying each day, more than the wave of the Delta variant that preceded it. What can we expect this winter as the virus continues to mutate? Here with me to discuss this is first, Dr. Verity Hill, a post-doctoral researcher studying viral evolution at Yale. Welcome, Verity. Thank you so much for joining us.

VERITY HILL: Hi, nice to talk to you again.

KATHERINE WU: It’s great to have you here. So let’s just dive right in. We’ve seen reports on this alphabet soup of sub-variants all coming out of the Omicron lineage this year. There is BQ-1, BQ-1.1, BF7, XBB. And all of these sub-variants seem to be, just in general, getting better and better at dodging our immune defenses. What would you say is going on in terms of viral evolution?

VERITY HILL: So at the moment, what kind of seems to be happening is we’re seeing almost more of a return to what the evolutionary landscape looked like pre-variants. We’ve gone from having one variant that is really sweeping the world in terms of Omicron, and to some extent, Delta. So what we’re seeing now is this wide range of lineages, like you say. In the UK at the moment, no one lineage is accounting for more than 12% of the sequenced cases. So the virus is kind of diversifying again after being locked into one variant.

KATHERINE WU: How do we deal with this, compared to what we’ve dealt with before, having one Greek letter variant hitting us at a time? Does that change our strategies? Or does that tell us anything about how the virus is shifting its strategies?

VERITY HILL: It’s harder for us to anticipate when some of the waves might come. So if you have one variant that you see arising in another country, say, when we saw Omicron really get going in South Africa and Botswana. And then other countries knew that that was going to reach them sooner or later. And there would be another big wave. What we have now, because we have all of these different lineages that don’t seem to have much of an advantage over each other, it makes it harder to predict which ones, if any, are going to cause a big uniform wave like that.

KATHERINE WU: You sort of draw a comparison to earlier stages of the pandemic when there was this kind of mish mash of heterogeneity, different types of mutations cropping up all over the virus and producing different lineages. But certainly, one big difference now is there’s a lot that’s different about us. What would you say is different from the host side, the people side? And how is that sort of pressuring the virus to be successful in new ways?

VERITY HILL: Yeah, so the biggest difference is that the level of immunity in the population is now completely different to what it was in 2020. So in 2020, we had more viral diversity, partly because everybody in the population was susceptible, or almost everybody after that very first wave that happened in March 2020. So there wasn’t a lot of selection going on. Everything could just spread quite happily. There were a lot of susceptibles around to infect. And we actually saw with the first variant, alpha variant, the reason that was able to spread was actually not to do with immunity.

It was because it could just get to people faster. It was more transmissible. Whereas now what we’re seeing is we have this whole mosaic of immunity with people having been infected no time’s, up to, you hear about people being infected five or six times. We have different levels of vaccination status, whether people have been boosted, how long ago they’ve been infected or vaccinated because we know that immunity seems to wane to COVID as well. Our population is a lot more heterogeneous than it was in terms of its immunity.

KATHERINE WU: Right, so it sounds like we’re going to be in this kind of patchwork evolutionary race with the virus for a long time. We’ve seen variants gains and big advantages by transmitting better between people, or just being better at dodging antibodies. Are there other viral traits that you’re worried about that could make a new variant more dangerous? There’s been a lot of discussion about whether we’re going to see more severe disease, milder disease as the virus evolves. Is there pressure on the virus to go one direction or the other?

VERITY HILL: When we’re looking at these traits of transmissibility and immune evasion, the virulence is what we call it, the effect on the host. And whether or not that increases or decreases is connected to whether it allows the virus to transmit or be more immune evasive. So a virus that is extremely immune evasive might end up being more virulent and more damaging to a population because our vaccines aren’t protecting us so well, for example.

Or if, in order to be more transmissible, it has to change how it replicates in the body, then that can also lead to more virulence. One of the interesting things that happened when Omicron evolved as compared to Delta is that it shifted the cells at targets in the human body. It became a much more upper respiratory tract infection rather than a lower respiratory tract infection.

So that made it both less virulent– if it’s in your nose rather than deep in your lungs, that’s causing less damage to your body, but also much more infectious because if it’s right up in your nose and you have a runny nose and you’re sneezing, then you’re spreading virus. So that’s where virulence comes into that trait. So there are some things we can predict in general about upper respiratory tract infections being more transmissible but less damaging than lower ones.

But it’s not clear that, for example, an upper respiratory tract infection might then go on to cause some secondary side effects that aren’t so much to do with the transmission of the virus, but is still damaging for the host. Evolution is not, by any means, a perfect process. It’s very, very stupid. And it’s very short-sighted.

And the virus doesn’t care what happens to the host after it’s transmitted. So it’s certainly not true that it’s always going to go towards lower virulence. But it’s also not true that it’s definitely going to go higher. There’s 100 different trade-offs happening all the time with pathogen transmission. And it’s very difficult to predict which way these things will go.

KATHERINE WU: Right, so while we’re on the subject of disease severity, I think it’s time to expand the conversation into what’s happening out in the real world. Pediatric departments all over the country are seeing an early start to the standard winter respiratory virus season. And a lot of places are reporting some pretty rough symptoms in kids who are getting sickened with flu and RSV, another common virus that can be especially dangerous for little kids.

Flu and RSV have always been winter hitters in pre-pandemic years. But now they’re back. And we’re adding COVID to the mix. So what’s going to happen this winter? To help us unpack that we have Dr. Ibukun Kalu joining the conversation. She is a pediatric infectious disease expert at Duke University Medical School in Durham, North Carolina. Welcome, Ibukun. Thank you so much for joining us.

IBUKUN KALU: Thanks for having me.

KATHERINE WU: All right, so we’ve been talking a little bit about coronavirus variants and the potential for another wave. But we’re already in a pretty rough place with COVID. What would you say is the situation on the ground right now with kids and COVID?

IBUKUN KALU: Interestingly, we are seeing fewer cases as compared to what occurred in the summer, the spring, and even last winter. And then the other point here, which I think you’re alluding to, is that there are quite a few other viruses that are outpacing COVID. I think this week is the first week we’ve seen RSV cases increase past the COVID case count for the week.

KATHERINE WU: Wow, so that’s not exactly the good news I was hoping for when you started saying there’s less COVID. So having this early and big rise of RSV, especially, and maybe to some extent flu, in some parts of the country, that is pretty different from previous pandemic years. We had almost no flu the first year, hardly any the second year. Why are we seeing this big surge now? And what’s that going to mean for kids?

IBUKUN KALU: I think it has to do with the epidemiology of viral transmission. Our behaviors changed significantly in 2020 and 2021. And that’s not just related to what we did for sars-cov-2. How we traveled, how we sent kids to school, how we accessed the health care system, all changed. And that also impacted viral spread. The expectation is that, similar to what occurred in the Southern hemisphere, we will see more of routine viruses spread in 2022 because some of those behavioral changes, we’ve kind of done away with them. And we’re also just at a different point in the pandemic.

So we know that all of the routine viruses are coming back. I should note that in 2020, we saw zero influenza deaths. In 2021, we started to see more influenza deaths. But they were not on track with what we saw in 2019. And this has nothing to do necessarily with the virulence of influenza. It really had to do a lot with the spread in our community. So all of that has changed. And that’s where we’re seeing more spread, and particularly in children who have not really seen these infections in the last two years.

VERITY HILL: To follow on from that though, actually, so most of the influenza cases we have globally are influenza A. There is also an influenza B. And a strain of that actually went extinct during the pandemic because it’s less transmissible than influenza A. And we haven’t, I don’t think, seen it come back up this year. So it’s possible that our non-pharmaceutical interventions, so closing schools, masking, working from home, all of those sorts of things for COVID may have actually eradicated this particular strain of flu, which is pretty cool, I think.

IBUKUN KALU: Yeah, I completely agree. It was so exciting to see. Let me rephrase because, exciting from more of the scientific epidemiology part of things, to see that we could actually eliminate a virus from spreading out community just by taking actions that don’t involve pharmaceuticals. So I thought that was pretty exciting. On the depressing end, unfortunately, we diagnosed a case of flu B this week. So it didn’t really disappear. It’s still there, but much lower, or it’s a lot lower than it was before.

KATHERINE WU: All right, well, I mean, I think that shows two sides of the same coin, how much we can drive rates of certain pathogens down when we take these measures like distancing and masking. But as you’re both pointing out, now that we’ve let up on those behaviors, a lot of these viruses are coming back. And this means that kids will be facing multiple different viruses at the same time this winter. What’s it going to mean if kids start seeing multiple infections in a row, or even co-infections, getting, say, flu and COVID at the same time?

IBUKUN KALU: So going back to a point that was raised earlier, the way in which the virus infects our bodies might impact the types of symptoms we see. So for children in particular, we worry that, when a virus has a tropism or preference for upper airways, they can lead to a lot of inflammation along their tiny airways, occlude their airways, and lead to them requiring more support during the acute phase of the illness. So for example, an infant that gets RSV will likely create a lot of mucus, have a cough, runny nose, fevers, and be unable to eat.

I say that to set the stage for, thinking through an infant that gets RSV, and then two or three weeks later gets influenza, and then maybe adds COVID on the tail end. We know that kids can get back-to-back infections. And for the most part, the immune system can keep up.

But when there’s subsequent back-to-back injury to the tiny airway linings, and they don’t have space in between to recover, or you see a co-infection that leads to more severe presentation than if they were infected with one virus as compared to the other, that’s when we worry that we will see a higher burden of disease, more health care needs, more issues with health care access, and unfortunately, more severe outcomes, which we typically look at hospitalizations and deaths.

KATHERINE WU: This is Science Friday from WNYC Studios. I’m Katherine Wu, talking to viral evolution researcher Verity Hill and pediatric infectious disease specialist, Ibukun Kalu, about our next COVID winter. I mean, it sounds like we have a lot of things working against us this winter. How are you both feeling about winters yet to come? Could we be dealing with this dangerous mix of viruses in future winters, or will anything improve?

IBUKUN KALU: I’m eternally optimistic. I think things might improve. I don’t know where we’re going with the variants for sars-cov-2. But some of the other viruses can change, the circulating strain, each season. So I don’t know how that match-up will look like in the future. But with growing immunity in the community, with the fact that– to restate that, the toddlers in 2022, the infants that were born during the pandemic or are less than three years of age, have likely not seen a lot of common circulating viruses.

So that will not be the same next year or the subsequent year. It’s sort of a unique situation where we find ourselves in winter of 2022 that I don’t think will repeat itself each year. But we’ll always see viruses. They’re here to stay.

KATHERINE WU: Verity, anything to add?

VERITY HILL: It’s so hard to predict what COVID is going to do because we all– everyone gets it wrong. And I mean everyone. None of us were expecting the variant evolution to happen, or at least I don’t know of anyone that was, where we suddenly saw this huge clump of mutations come up at once like that. That doesn’t really happen very often. And the only times we know of it happening, like in flu with antigenic shift, is by a completely different process.

And it happens very rarely. So that was a shock. And then each time a new variant comes up, it’s also a bit of a shock. So it’s difficult to predict what’s going to happen on the variant evolution front. My feeling is that at some point, COVID will settle into a more seasonal thing like we see flu doing. And it’s clear that when children go back to school and people are more inside, you get new waves of infection, regardless of variants.

There’s just been quite a big wave in Germany that has absolutely nothing to do with the genomics of the virus, and is instead to do with human behavior and all of that sort of thing. So it’s difficult to tell because it feels like it should settle down. But there may be a new variant that comes in and gives us another wave in a time of the year where we wouldn’t expect respiratory illness to be so much of an issue.

IBUKUN KALU: I was going to add to that, that in this conversation, we’ve focused a lot on the virus, on the groups at risk and how we can prevent spread. If we do reach a point where we’re seeing multiple viruses spread at the same time and have an impact on communities, it is important to go back to that pandemic drawing board and ensure we have an infrastructure that can keep up with the varying spread, and can be flexible enough to ensure there’s access and there’s equity in providing care.

KATHERINE WU: Dr. Verity Hill is a post-doctoral researcher studying viral evolution at Yale University’s School of Public Health. And Dr. Ibukun Kalu is an Associate Professor of Pediatrics at Duke University Medical School. Thank you both so much for joining me today.

VERITY HILL: Yeah, thank you.

IBUKUN KALU: Thank you.

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