S1E61: A More Contagious and Virulent Variant (UK Edition) / Andrew Hayward, Trevor Bedford, Gard Nelson, Graham Medley

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This winter a new, more contagious variant of SARS-CoV-2 arose in the United Kingdom: B.1.1.7. The CDC estimates that this will become the dominant strain of coronavirus in the United States by March. This is the first of several episodes on the science and policy implications of the new coronavirus variants emerging out of the UK, South Africa, and Brazil. This episode will discuss how new variants are created, why we need to worry about B.1.1.7, and what this all means for public health in the coming months.

“I had been assuming that my life and everyone else’s life would get closer to normal in March. This [variant] has me worried that it won’t be March, that we’ll have a spring wave and I don’t know how big that will be.” -Trevor Bedford

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Andrew Hayward: All strains of COVID really have the potential to cause it enormous disruption.

Graham Medley: And the more viruses you have the greater the chance that you actually have a variant which is going to evolve around what you’re doing.

Céline Gounder: You’re listening to EPIDEMIC, the podcast about the science, public health, and social impacts of the coronavirus pandemic. I’m your host, Dr. Celine Gounder.

This winter started with a lot of hope…

News clips about vaccine efficacy rates: Breaking News! Pharmaceutical giant Pfizer just announced, moments ago, that its Coronavirus vaccine is 95% effective, and that they will apply for FDA emergency use within days.

CG: The FDA approved the Pfizer vaccine for emergency use on December 11th.

The FDA says its review of the data suggests Pfizer’s COVID vaccine is very promising. 

CG: And then the Moderna vaccine got approved soon after.

For the second time in just over a week, a panel of scientists advising the US Food and Drug Administration recommended another COVID-19 vaccine, this one produced by Moderna, which is 94% effective. 

CG: But around this same time, something was stirring in the United Kingdom.

Andrew Hayward: So I think the first sign that this really was, we were in a period of lockdown…

Céline Gounder: This is Andrew Hayward. He’s the Director of the University College of London Institute of Epidemiology in Health Care.

Andrew Hayward: And what we could see was that in one area of Southern England in Kent, there were increasing rates of the virus, despite the tight control measures, whereas in other areas, everything was going down and we couldn’t really understand that.

Céline Gounder: Everywhere else the lockdown was leading to a decrease in transmission, but not there. What was going on?

Andrew Hayward: When Public Health England looked in more detail at that, and also were able to look at some of the genomic sequencing data that they could see that this was an increase that was in one particular genetic variant of the virus. So that’s really where this all started.

Céline Gounder: This new COVID variant found in southeast England was named B.1.1.7.

Andrew Hayward: And they could see that actually it was growing not only in Kent where it first originated, but also in other parts of Southeast England and in London and the East of England. But subsequently when the new strain came into those other areas in the North of England, for example, we could see very rapidly that it started to rise to be the dominant strain in those areas, too.

Céline Gounder: Posts started to show up on virology forums about this new variant. Trevor Bedford took notice.

Trevor Bedford: The main thing that had me take notice was the Andrew Rambos virological posts. So virological.org is kind of a discussion forum for people interested in this sort of stuff.

Céline Gounder: Trevor is a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle. The news was pointing to some very weird mutations in the virus that had troubling implications for the pandemic.

Trevor Bedford: So the evidence seems convincing that we’re talking about something like a 30%, perhaps even 50% increase in infectiousness and transmissibility of B.1.1.7.

Céline Gounder: Trevor didn’t believe what he was reading at first.

Trevor Bedford: So my prior coming into things, from work on Ebola and seasonal flu and other viruses, is that like a jump to become 50% more transmissible is, is really difficult. And so the first evidence, the first kind of findings here, took a lot to kind of get over that, that prior expectation.

Céline Gounder: But over the last two months, more and more reports agree that the UK’s B.1.1.7 variant is much more contagious — and perhaps even more virulent — than earlier strains of SARS-CoV-2. Just last week, on February 7th, a preprint of a report on the UK variant’s transmissibility came out. It supported earlier modeling from the CDC that B.1.1.7 would become the dominant SARS-CoV-2 strain in the United States by March.

Trevor Bedford: I had been assuming that that my life and everyone’s lives and would get closer to normal, and people wouldn’t be dying so much in March, where things would slow down. And then this had me worried that it won’t be March – that we’ll have more of a Spring wave and I don’t know how big that will be.

Céline Gounder: This is the first of a couple episodes on the science and policy implications of the new coronavirus variants emerging out of the UK, South Africa, and Brazil. Today we’re going to focus on the UK variant that is already spreading widely in the United States.

We’re going to find out why these variants are so surprising…

Céline Gounder: And as you’re reading these news reports of the UK variant, the South Africa variant, you know, what’s going through your mind as you’re reading this?

Gard Nelson: That wasn’t supposed to happen yet. [laughs]

Céline Gounder: What’s so different about the UK variant…

Trevor Bedford: It’s actually kind of becoming better binding to ACE-2 [receptors on cells] and getting into cells quickly. So it looks like this is kind of a fundamentally fitter virus.

Céline Gounder: And what we need to do to prevent another devastating wave of the virus.

Andrew Hayward: If you carry on doing the same thing, you will end up with a bigger epidemic, with more deaths.

Céline Gounder: Today on EPIDEMIC, the rise of the UK variant.

Viruses mutate all the time. The same goes for SARS-CoV-2.

Trevor Bedford: SARS-CoV-2 mutates really quickly, just like any RNA virus. It has 30,000 letters and its genome. And if you follow a transmission chain, one of those will change on average every two weeks.

Céline Gounder: But this natural process was put on fast forward in countries like the UK, South Africa, Brazil, and the United States that have struggled to control the virus. Basically, the more the virus spreads, the more opportunities there are for mutations to occur. But if there are enough people with partial immunity, that… can also… drive these adaptations.

Trevor Bedford: If we look at the U.S. there has been, perhaps 20% of the country has been infected by SARS-CoV-2, and that makes it so that infections today, will likely encounter individuals who have been previously infected, and it puts evolutionary pressure on the virus to be able to infect those individuals.

Céline Gounder: The seasons can drive these mutations too.

Trevor Bedford: So in the case of SARS-CoV-2, if you think about these basic evolutionary pressures, it should want a high enough viral load that it’s able to easily transmit from person to person. Versus if it gets too high in viral load, you’d imagine that someone ends up sick in bed more quickly as they’re not kind of out and about spreading the virus.

Céline Gounder: So, between the seasons, some level of partial immunity in the population, and areas where there are large outbreaks, there are lots of ways a virus can change.

Andrew Hayward: Essentially, it’s got to outcompete the old strains, and it can either do that by becoming more transmissible, or potentially through evading immunity.

Céline Gounder: These are both troubling possibilities. But for the UK variant, Andrew says it didn’t seem that B.1.1.7 was better at avoiding the body’s immune response.

Andrew Hayward: In the UK, at the time that this strain was emerging, the proportion of people who had any evidence of antibodies to COVID was relatively low in most parts of the country. It’s unlikely to become the dominant strain through evading immunity if only a small proportion of the population are immune anyway. So immediately, we were thinking that it was likely to be increased transmissibility that can affect that.

Céline Gounder: So far, the part of the coronavirus where these concerning mutations are popping up are on the spike protein. Gard Nelson is a senior research scientist at Immunity Bio. Gard and his colleagues have been studying how the mutant SARS-CoV-2 variants escape the immune system.

Gard Nelson: Any mutations in the spike protein can change what your body sees and if it changes what your body sees enough, then your body may not recognize it may not be able to fight it off. These mutations can have a big impact, particularly in how the virus spreads.

Céline Gounder: The spike proteins jutting out of the coronavirus give it its unique shape.

Gard Nelson: So at the very top of the spike protein, kind of the tip of the spear, is what we call the receptor binding domain.

Céline Gounder: The spike protein looks for a place to grab on to your cells.

Gard Nelson: When you look at these things, how they move, they kind of seem like kind of blobs of Jell-O, and so you bring these two blobs of Jell-O together, and when they come together in the right way, they stick. Well, as you make mutations to one of the blobs of Jell-O, it can change how they like to stick together. It can rotate it or shift it a little bit. And what that can do is it can bring different parts of that protein close enough to where they can start to be impactful.

Céline Gounder: This is where the big change happened in the UK variant. The B.1.1.7 variant found a new, better way to grab hold of our cells. That spot the coronavirus looks for on a human cell is called the ACE-2 receptor.

Trevor Bedford: So the virus really what appears to we’ve seen with the variants of concern is by getting better at binding the ACE2 it reaches higher titers, higher viral load within a person and is able to spread from that person to the next more easily.

Céline Gounder: This mutation is the key to the UK’s B.1.1.7 variant’s success. More virions…  getting into more cells… faster than ever. And this leads to the next big question — is a more contagious virus… a deadlier virus?

We’ll hear what this variant means for people who get sick, and what we know about its ability to evade our vaccines. That’s after the break.

* * *

Céline Gounder: We know the UK variant is more contagious… but does it cause more severe disease?

Graham Medley: Having found this new variant, then the next question and knowing it’s more transmissible. The next question. obvious question is well, is it the same virus? Is it giving you the same symptoms? Is it causing different diseases?

Céline Gounder: This is Graham Medley. He’s a Professor of Infectious Disease Modeling at the London School of Hygiene and Tropical Medicine.

Graham Medley: And of course it might actually be less dangerous. Uh, there’s no reason why a virus is better at transmitting it should necessarily be more dangerous.

Céline Gounder: So public health officials tried to figure out if the mounting deaths from the new variant were because more people were getting sick… or if B.1.1.7 was in fact causing more severe disease. This is a difficult thing to figure out. In epidemiology, we worry about what are called confounding variables.

Graham Medley: So confounding is where you have something that’s both related to the cause and to the effect. So in this case, you’ve got a virus which is growing, increasing in prevalence at the same time as hospitals are getting fuller. So the fact that people are more likely to die, could be because treatment in hospital gets worse as they get fuller, or it could be to do with the new variant but, but they’re all related in time.

Céline Gounder: So public health officials started doing case studies, tracking how people fared with the different variants.

Graham Medley: And all those approaches essentially give us the same answer, which is that this virus does increase the chances of deaths by about 30%.

Céline Gounder: This 30% increase of death depends on other risk factors. Here’s Andrew Hayward again:

Andrew Hayward: A 30% increase in case fatality rate means quite different things at different age groups, because, of course, the absolute risk of death is much, much higher in the very elderly, whereas in young adults, for example, where you’ve got very, very low rates of death, then a 30% increase in a very, very low rate is really very little.

Céline Gounder: So, a 30% increase in risk of death is much more serious for someone in a nursing home, let’s say, than for a healthy high school student. But for a virus that’s already caused so much death… a 30% increase in fatalities is troubling.

But Graham says there does seem to be one bright spot about the B.1.1.7 variant.

Graham Medley: At the moment, there isn’t any clear evidence that this UK variant can actually overcome immunity any better than any of the other viruses so that’s something, which I think is encouraging.

Céline Gounder: The increased risk of transmission and death has led the UK to change the way it’s rolling out vaccines. They’re trying to get as many people as possible their first shot… even if it means waiting longer to get the booster recommended by Pfizer and Moderna.

Graham Medley: The kind of basic logic behind it was that if one dose gives you more than 50% protection, then you protect more people by vaccinating with a single dose than you would by vaccinating half the people with two doses. One of the deputy chief medical officers in the UK, I think gave a really good analogy, which has said that, you know, let’s say you had two doses and you have two grandparents; which grandparent are you going to give the two doses to? Or are you actually going to share out that immunity and give them one dose each.

Céline Gounder: One critique of this approach is that partial vaccination could mimic the kind of evolutionary pressure we spoke about at the top of the show… and drive new variants.

Céline Gounder: Any reason you could make the situation worse by vaccinating?

Trevor Bedford: Um, I don’t think so.

Céline Gounder: Trevor Bedford again.

Trevor Bedford: Worst case scenario, which I don’t actually believe in, vaccination with a partially effective vaccine, you could more quickly pressure the virus to switch dominance from wild type to variant virus, and you need more quickly update your vaccine strain, which isn’t isn’t that all the end of the world.

Céline Gounder: And then sort of the flip side, in some ways, is this a scenario where you could argue to people that vaccination is better than natural infection?

Trevor Bedford: Yes, certainly. There’s kind of two things that we often think about in terms of the rate of evolution. One is this immune pressure. So adding vaccination increases immune pressure. Adding natural infection increases immune pressure. The other is just the amount of circulating virus in the world, and the more circulating virus there is, the more chances they have to mutate and to into to escape from immunity and to evolve. And so natural infection increases the amount of virus that’s in the world rather than decreasing it like vaccination does. And so even though both will create more immune pressure having something naturally spread will give it much more opportunities to kind of increase frequency of the variant.

Céline Gounder: And then how do we prevent new variants from emerging?

Trevor Bedford: Yeah, um, also – also tricky. I think the like entire aim right now should be vaccinating as many people as possible, as quickly as possible to get circulation down.

Céline Gounder: As vaccine rollout continues, whether to spread out supply by focusing for now on first doses remains hotly debated. I worry that partial immunity could put immune pressure on the virus to mutate more. So what else should we be doing to slow the spread of coronavirus and these new variants? Graham says we already know.

Graham Medley: The virus hasn’t changed the way it’s transmitted. So all the interventions that you put in place, you just need to do those interventions that you’re doing more because this virus is just more transmissible, and it’s more dangerous. So you will end up, if you carry on doing the same thing, you will end up with a bigger epidemic with more deaths.

Céline Gounder: That means wearing a mask and sticking as much as possible to household bubbles and well-ventilated spaces. Andrew agrees. He stressed the need for decisive action when a new variant of concern is discovered.

Andrew Hayward: The countries that have done well took really aggressive measures early on, and whenever they see a resurgence, still take really aggressive measures, and those societies are functioning pretty much as normal.

Céline Gounder: Andrew’s talking about countries like Australia. That nation has been able to return to some sense of normalcy with relatively few deaths. But this month, the entire city of Perth went into lockdown after reports of a single case.

Andrew Hayward: I think there’s a big tendency for governments to, because they want to protect people’s livelihoods and freedoms and the economy, then they leave it until the last minute, if you like, before they take decisive action to prevent spread. A small fire, it allows it to become a big fire, and we all know how hard big forest fires are to put out. And so you end up with more deaths, and it ends up taking longer to put out, and ultimately it ends up damaging your economy more.

Céline Gounder: So far, the Pfizer and Moderna mRNA vaccines have performed well against the UK variant. But researchers recently found a new mutation in B.1.1.7. A change in the spike protein that looks a lot like other strains we’re concerned about: the South Africa and Brazil variants.

In late January, the U.S. reported its first cases of the South Africa and Brazil variants. We’ll hear about the science and public health implications of these variants, next time, on EPIDEMIC.

 

CREDITS

EPIDEMIC is brought to you by Just Human Productions. We’re funded in part by listeners like you. We’re powered and distributed by Simplecast.

Today’s episode was produced by Zach Dyer and me. Our music is by the Blue Dot Sessions. Our Production and Research Associate is Temitayo Fagbenle. Our interns are Annabel Chen, Bryan Chen, and Julie Levey.

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I’m Dr. Celine Gounder. Thanks for listening to EPIDEMIC.

Guests
Andrew Hayward Andrew Hayward
Gard Nelson Gard Nelson
Graham Medley Graham Medley
Trevor Bedford Trevor Bedford
Host
Dr. Celine Gounder Dr. Celine Gounder