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All Podcasts Toolkit: What You Need to Know About the Variants

Toolkit: What You Need to Know About the Variants

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If you were worried that a new host would mean a completely different show, let this Monday Toolkit ease your fears. Dr. Bob poses your questions about the so-called UK and South African variants to virologist Angela Rasmussen and evolutionary biologist Paul Turner. You’ll get answers about what the variants mean for the vaccines, how they affect kids, how to adjust your behavior in response to them, and much more.

 

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Transcript

SPEAKERS

Dr. Paul Turner, Dr. Bob Wachter, Dr. Angie Rasmussen

Dr. Bob Wachter  00:00

Welcome to IN THE BUBBLE. Okay, we’ll try that one again. Welcome to IN THE BUBBLE. I’m Dr. Bob Wachter filling in for Andy Slavitt. If you missed Friday’s show, you may be wondering did Andy go? And so quick, quick summary is Andy has accepted a short-term role being a senior advisor to the Biden administration on COVID. I am grateful to him for doing that, because we need him and his expertise and his empathy to try to get us out of the pickle that we find ourselves in. He has given me this amazing opportunity to babysit this wonderful show. I’m an avid listener, I’ve learned a ton. So it’s extraordinary opportunity to have the chance to host it and I’ll be doing that.

Dr. Bob Wachter

Today is a toolkit episode. And we take your questions and then bring to the show a couple of the world’s experts on this. And we’ve done that today, in a discussion about the new viral variants. It’s obviously a terrible and sad time in the country. And one way of measuring that is, even though we’re having deaths from COVID, that are the equivalent of 9/11 every single day, that’s not even been the top story in the news for the last couple of days, as we’re all grappling with the aftermath of what happened in the Capitol and what it means for our political system and democracy.

Dr. Bob Wachter

I’ll tell you, when I first heard in November, that we had one and then two vaccines that were 95% effective in preventing cases of COVID. I had a number of media interviews asked me how I felt and the answer was euphoric, I couldn’t believe it. And yet the vaccines are rolling out far more slowly than they should be. And hopefully, we’re going to get on top of that. But the last month has been somewhat disheartening in that regard. And the second bit of at least potentially bad news is the reports that we’re all hearing about these new viral variants. As you’ll hear viruses mutate all the time, most of the mutations are benign. I’ve spent the last 10 months telling people yeah, they mutate all the time. Yeah, they’re a little bit different. But they’re like little typos. And a very long document that really doesn’t mean very much.

Dr. Bob Wachter  02:08

But that answer is no longer accurate, unfortunately, and just another case in COVID that were surprised and things change. And that’s what science does, we learn new things. And we now do have at least a couple of variants that are different. But these two stories, the slow rollout, and the variants are connected, because now we’re not only in a race against COVID, the virus that we’ve come to know and hate over the last year to get as many people vaccinated as possible. But we’re now in a different, slightly different race against a competition that’s running faster than it was before. So we have to run even faster to get people vaccinated, and get on top of this.

Dr. Bob Wachter 

So we’ll be talking today about these new viral variants and what they mean for the shape of the pandemic in 2021. I am really thrilled that we were able to speak with two World Class experts, and one is Angie Rasmussen, who has been on the show before. Angie is a virologist who studies emerging viral host responses. And really one of the top virologists in the world, very, very prominent on Twitter. And her account, as far as I know is unlocked. She’s with the Georgetown Center for Global Health Science and Security. And he’s going to be joined with another really remarkable guest, Paul Turner, who’s an evolutionary biologist and virologist if you don’t quite know what an evolutionary biologist is.

Dr. Bob Wachter

It’s someone who understands and helps us understand this idea of mutation and what it means. He’s the Rachel Carson professor of Ecology and Evolutionary Biology at Yale and a professor of microbiology at the Yale School of Medicine. I really enjoyed talking to these two guests and learning from them. And I think you’ll enjoy it as well, although some of the news that we’ll hear is kind of hard. They are both incredibly smart, thoughtful, they’re terrific teachers, because some of the stuff is pretty complicated. But one of the things that impressed me the most is how empathic they are.

Dr. Bob Wachter  04:01

You can tell that these are two individuals and scientists that spend their day looking at sequences and looking under microscopes. But they deeply understand the impact of this is an impact on real people and their families and their communities. And so, really grateful to them for being with us on the show today. And let’s go ahead and bring on Angie Rasmussen and Paul Turner.

Dr. Bob Wachter 

Hello.

Dr. Angie Rasmussen

Hi, Bob.

Dr. Paul Turner 

Hi, everybody.

Dr. Bob Wachter 

How are you?

Dr. Angie Rasmussen 

I’m good.

Dr. Paul Turner 

Good. Thanks.

Dr. Bob Wachter 

All right. We’re ready to go.

Dr. Angie Rasmussen

Yep.

Dr. Paul Turner 

Sure.

Dr. Bob Wachter

So welcome to both of you.

Dr. Angie Rasmussen 

Thank you, Bob.

Dr. Paul Turner

Thank you.

Dr. Bob Wachter

Let’s start out by sort of acknowledging the challenges of calling these variants by their real numbers and names so at least I am inclined to call them the UK variant and the South African variant versus N5014B117. Is that okay? If we do that?

Dr. Angie Rasmussen 

That’s fine with me.

Dr. Paul Turner 

That works for me as well.

Dr. Bob Wachter 

All right, so we will call it that. So Paul, why don’t you start us off and tell us about viral mutations. And I understand viruses mutate all the time. And yet, last year, we seem to be saying “oh, no big deal.” And now we’re saying big deal. So tell us about how mutation happens in that we’ll get into what has happened.

Dr. Paul Turner 

Sure, in any biological population that is making copies of itself either on its own or, as in the case of viruses, they instruct cells to make these copies. mutations are inevitable. This is just what happens when you replicate nucleic acid, DNA and RNA. So in short, the power of evolution is that if you have very large population sizes, if you have lots of genomes that are being replicated, mutations will occur. And if this is happening in the millions and billions, then occasionally, you’re going to get some variants that has mutated and it is more fit in some way than the variants that it is descended from. So this is what we’re seeing. And it is not surprising. And we’re trying our best to, of course, deal with the pandemic with this new information.

Dr. Bob Wachter  06:14

Sounds like the variants we’re going to be talking about are nastier in various ways. I imagine there are good ones, too. And what determines whether a nasty one wins out a good one wins out or kind of both.

Dr. Paul Turner 

Right, of course evolution is blind, it uses what’s at its disposal, and variants interact with their environments, and they get an advantage if they can. So the listeners here who maybe don’t know as much evolution and genetic change, essentially, these mutations in any biological system are expected to mostly break things and make them worse. Okay, so the number of harmful mutations that pop up are far more than the number of neutral ones or beneficial ones. But the key question is beneficial to whom, if these are mutations that are good for the virus to transmit and make it into new host individuals, more humans than that’s good for the virus.

Dr. Paul Turner 

Certainly, that’s bad for us, because this is creating more cases. So I guess we just have to remember what evolution is doing here. These are variants that are seeing a new environment, and that new environment is the ability to replicate in humans. So we’re going to see some of these good mutations, if they could become prevalent enough that we detect them. And my hope has been that, you know, what you see sometimes in Coronavirus, is that they’re quite benign in or you have even mild symptoms. These are the ones that are not the SARS, coronaviruses, etc.

Dr. Paul Turner 

So, you know, it could have been the case that the mutations that we find the variants that are popping up are actually milder. Fortunately, we’re seeing there’s no difference in these variants for the most part. I know we’ll talk about that today. But basically, it could be worse. And my hope is that we can still, as long as the vaccine is working on the strains, which I’m sure we will talk about, then I think we’re okay.

Dr. Bob Wachter  08:05

We will and the milder piece is interesting, because I guess in my simplistic way of thinking about it, if it’s milder you mean by milder in terms of causing a milder disease not being milder in terms of infectiousness because that’s being more infectious, I would assume gives it a selective advantage in terms of taking over a human population.

Dr. Paul Turner 

That’s right. So the dizzyingly difficult thing with any virus system but certainly risk, this one is that as we learn about its traits, it still surprises us, because we don’t know what we’re dealing with. And as new variants come on board, it is quite frightening, because we would like to know that the past information that we spent so much time amassing is actually going to be useful for understanding these variants. We are better poised to do now than we were roughly a year ago is to do experiments in the laboratories around the world and interpret the data with some at least foundation to understanding what we’re observing.

Dr. Paul Turner 

So it’s not as if we’re flying completely blind all over again, this is what worries me when people talk about “Oh no, does this set us all the way back to the starting point?” And I would say necessarily, it does not. It builds on information that we’ve been using a lot of human energy to amass over the past 10-12 months. And therefore, you know, we’re in a better shape in order to interpret these data and do something about it. But I hope that was somewhat of a useful response to your question.

Dr. Bob Wachter 

Oh, fantastic, incredibly useful, and you explained things very, very clearly. I appreciate it. And also, I appreciate the reassurance because there is it doesn’t take much of a leap of imagination, to say, oh, my goodness, you know, we are back to square zero and things are out of hand again, and as 2021 going to be 2020, maybe worse. So I really do appreciate that. Angie, let’s turn to you and take us through these new strains that we have identified and it feels like at least in the press that I read, there is the strain we’ve all come to know and not love over the past year. And now the UK variant and then the South African variant, maybe there are more that you want to tell us about, but take us through them and what we should know about them.

Dr. Angie Rasmussen  10:14

Yeah, so I think what people should understand first is that the strain or variant that we’ve all come to know and not love, is actually a whole bunch of different variants. And that’s the thing about RNA viruses, they exist, first of all, inside a host as what we call quasi species. So there’s already a bunch of different variants, even within a host. Now, probably, that’s to a lesser degree and coronaviruses than for something like HIV, both because coronaviruses cause acute infections. And also, they have a partial proofreading capability, meaning that they’re when they make the typos that are mutations.

Dr. Angie Rasmussen 

They have an enzyme that can go basically do a partial spellcheck, and correct some of those. But that said, they’ve had a lot of opportunity to replicate. And so a number of different variants have emerged. And that’s been used to really track the spread of the virus throughout the world in places where they have done genomic surveillance. The big difference with these variants is that they’re also associated with an increase in transmission. And that’s something that we haven’t seen. So some of them both the UK and South African variants have a mutation in the spike protein. It’s the part that binds the cellular receptor and allows the virus to get into a cell.

Dr. Angie Rasmussen 

And that may be contributing to what makes these variants more transmissible. But it’s important to note that we don’t actually know that right now, all we have is epidemiological evidence that these variants became prevalent in certain populations, where they were first detected very, very quickly, much more quickly than other variants that were circulating at the time suggesting that there is a competitive advantage that those mutations confer. But we don’t really know what mechanism that’s happening by/

Dr. Bob Wachter

I guess your description is that it’s stickier, or that if we think of the spike protein is a lock and key mechanism, this is just a tighter connection than the original virus.

Dr. Angie Rasmussen  12:10

That’s exactly right. Although, I will caution that those are with binding studies, that’s very difficult to look at in a systematic and quantitative way when you’re actually infecting cells with the whole virus. So just because a locking key fits better together doesn’t necessarily mean that it’s going to open more doors, it could be that that’s important. And it also might not have any effect on it, it could just be that people are shedding more virus. And with a previous variant that a lot of media attention was given to earlier this year.

Dr. Angie Rasmussen 

The D614G spike mutation that does appear to increase at least in hamsters, nasal viral loads, significantly, and it does appear to transmit more quickly in an experimental model, but it hasn’t become dominant as quickly as these new variants that we’ve detected. So it’s complicated. It’s not as easy as just saying, aha, there’s a mutation, it looks like it’s an important part of the protein. It looks like it might do this. So that’s probably what’s causing it. It’s a lot more complicated than that.

Dr. Bob Wachter

Yeah. Yeah. And I appreciate you calling out the hamsters because they had a very tough 2020 as well. And I don’t think we give that enough attention

Dr. Angie Rasmussen 

They sure did.

Dr. Bob Wachter

Yeah, let’s, one of our listeners, Karen asked a question that is relevant now. And she said: “I’ve heard that the amount of virus in the initial exposure may be related to the severity of illness. If the UK variant is associated with higher viral loads, why isn’t it associated with a higher severity of illness or fatality rate.”

Dr. Angie Rasmussen

So the notion that inoculum size is directly related to the disease severity is a hypothesis that’s been proposed. But there’s actually not that much evidence to suggest that that’s true, at least not based in animal models. But we’ve seen in animal models and granted animal models are imperfect. But we’ve seen that basically, it drops out to either the animals are not getting infected at all, or they’re all pretty much getting infected and having the same type of disease severity. Sometimes there are some differences in the rate at which disease onset occurs. The only thing to keep in mind about this, however, is the animal models are not perfect representations of human disease.

Dr. Angie Rasmussen  14:27

But one thing people should keep in mind is that viral load is actually different than inoculum, or infectious dose. So people can have different viral loads for variety of reasons. Let’s say you and I get infected with the same dose of virus, but my immune system is just more robust than yours for whatever reason, I will have lower viral loads, you might have higher viral loads, you might get the virus spreading to different tissues, I might not or vice versa. So one thing people should keep in mind is that viral load isn’t necessarily representative of the dose that you were exposed to. Now, I don’t think we can rule it out that inoculum size does have an ultimate downstream effect on disease severity or outcome.

Dr. Angie Rasmussen

But it’s just really hard to tell right now what my personal speculation would be is that this is more it is more transmissible because people are being exposed to a higher dose of virus, that means they’re just going to be more likely to get infected, it doesn’t necessarily mean they’re going to have more severe disease. Unfortunately, the epi data so far about these variants suggests that they aren’t any more pathogenic. The real risk with these is that we might overload our hospital systems, because so many more people are getting infected, not because they’re getting infected with something that causes super COVID.

Dr. Bob Wachter 

So let’s just spend a minute on this inoculum idea, because I’m confused by it, people are always confused by it, you tend to think that if I go out and one viral particle lands on the back of my nose, I’m gonna get COVID that we now I think, understand that that’s not true that you need 1000s or 10s of 1000s. And part of the reason that masks work is you may still get a particle or two, but maybe not hit that threshold. So is the point that the person who I’m exposed to who has this variant is more likely to expose me with more particles or that a given particle is more likely to burrow into the back of my nose.

Dr. Angie Rasmussen  16:22

I would say that it’s you’re more likely to be exposed to more particles. Because really, it becomes a numbers game. And some of the protections you have against becoming infected with a virus via the respiratory route, are things that a virus can’t really evolve to get around something like a mask, A virus can’t evolve to get through a mask. You know, mutation does not make a virus an x man, it doesn’t make it capable of transcending a physical barrier. And the same is true for other physical barriers in your nose, such as the mucous layer that’s on top of the cells in your respiratory tract, or your nose hairs, even that can prevent some particles from getting further down into your respiratory tract.

Dr. Angie Rasmussen 

So some of the barriers that are there are completely physical barriers that have nothing to do with a virus and the virus can’t really mutate around it. Now, that’s not to say that, you know, the virus could become more infectious, meaning that you would have a lower number of virus particles that you would have to overcome those barriers to cause a productive infection. And that could be what’s happening here, we can’t rule that out. But my guess would be that it’s just that you’re increasing your risk. In terms of strict probability. If you’re exposed to more particles, you’re more likely to get infected.

Dr. Bob Wachter 

Great, thank you. Paul, anything you want to add to that?

Dr. Paul Turner 

That was terrific. I mean, that was very well put. And, you know, I had this discussion with somebody just earlier today, and he was a reporter. And he had asked someone, you know, would you rather the virus be more dangerous and have a higher risk of causing you individual mortality? Or, you know, would you choose behind curtain B. And, you know, and say that, hey, this is something that’s more transmissible. And what Dr. Rasmussen just said is just spot on. I mean, the issue is, especially here in the US, as we’re facing medical systems that are pushed to their limit. And now trying to get beyond that limit.

Dr. Paul Turner  18:22

The issue is that more and more people as they become sick, necessarily, this means that more people can die, because more people are sick. And that’s a very difficult thing for people to weigh, you know, what’s the risk of that me going to a dinner party, versus what we are not seeing there is no evidence to say that these invariants are more dangerous to you as a person, but it increases the probability that you might get sick and therefore it increases the probability that you might be one of those who responds in a very poor way, physiologically, and through your immune system.

Dr. Bob Wachter 

Yeah, I would love for there to be a choice. See, like neither of these happen.

Dr. Paul Turner

Yeah, I would, I would love that, too. I take your point. And it’s interesting, that’s a hard thing.

Dr. Bob Wachter 

I think for a lot of people to get their arms around that it is not any more likely to put you in the hospital or to cause your death than the old variant. But if you are much more likely to get infected, then more people will go to the hospital and more people will die sadly, and they feel like it shouldn’t be one or the other. But you know, the case rates will drive bad things including hospitalizations, and ICUs and deaths.

Dr. Paul Turner

And if I might add quickly to that, of course, what we’re hearing is the unfortunate thing is an emergency room might be closed in your area. Right? And therefore it may have nothing to do with actually the virus but you can’t get treatment for something that you need.

Dr. Paul Turner

Yeah, that’s obviously part of it.

Dr. Bob Wachter 

Yeah.

Dr. Bob Wachter

Connecting the dots is important that there is a prevalence above which systems begin to fail. And so even if the virus itself is no nastier as those systems fail, the chances of a bad outcome have to go up. So if the ER is overloaded if the ICU is packed, if contact tracing can’t work anymore, because the contact tracing system is overwhelmed, then the outcome may be worse even if the virus is doing exactly the same thing it did six months ago.

Dr. Bob Wachter  20:29

Well, let’s turn to what people can do about this. Because obviously, that’s what we’re all concerned about. So take us through maybe Angie you can start take us through now that we know this, that this variant is around. And as you say, we’ve been flying blind a little bit. We’ll get to that a little bit later. But we don’t know how much it’s around. But we know that it’s probably around. If I have over the last 10 months come up with a set of strategies for myself and my family about what I will and won’t do. Do I wear one mask or two? Do I go to the store? Or do I not? How much do I need to rethink those strategies?

Dr. Angie Rasmussen 

Well, here’s the problem that I see anyways, is that there isn’t really one consistent strategy that people are putting together. Because the one thing people should keep in mind and I think when people hear again, you know, the media coverage of this is like, Oh my god, the virus is mutated. Oh my god, It’s more transmissible. People start to think that you know, and then there are people quoted out of context, I’m sure because I can’t imagine why somebody would say “Oh, lockdowns aren’t going to work.” Not to say that I’m advocating for a lockdown. I don’t think we can have that at all without providing support for people that would enable them to do a lockdown.

Dr. Angie Rasmussen 

But I think that saying something like lockdown won’t work. Implies to people that this virus is suddenly insidiously sort of got a mind of its own. And now it’s going to get into your house, like you can board up the windows, it’s like something in a horror movie. And the thing is, when this virus is we don’t know the mechanism by which it’s more transmissible, but it doesn’t seem to be transmitted by some new route, it doesn’t seem as though all of a sudden, this is now blood borne, or sexually transmitted. Or at least, oral fecal transmission is not a more significant contributor than, I guess, potentially aerosol fecal transmission, which has been suggested in a couple cases.

Dr. Angie Rasmussen

Really, this is still a respiratory virus, it’s still causing the same disease, it’s still infecting people by the same root. So what people need to be thinking about is really doubling down on the measures they should have already been taking. And here’s why it is a problem that we haven’t really had consistent guidance. You know, a lot of people, a lot of scientists, including myself, and clinicians have gotten excited about the Swiss cheese model that we’ve all seen. Showing that really all these different risk reduction measures are additive, the more you can apply, the better. Because we haven’t had a lot of strong national guidance from our leadership, I think people have sort of picked and chosen different measures that they can apply for themselves. And unfortunately, some of the measures have also been politicized, which creates more of a problem.

Dr. Angie Rasmussen 

But my advice to everybody about this is to double down and be extra vigilant about those same measures. So avoid gatherings, stay home, if possible. If that’s not possible, make sure you’re always wearing a mask, make sure you’re physically distancing, if you can ventilate the space that you’re in, that’s wonderful. If you can limit the time that you’re around people who are not within your household, that’s also wonderful, be conscious of hand hygiene and try to disinfect high touch common surfaces. If we really reiterate to people that these are the measures that you can take against these new variants, as well as any other variants that might emerge as well as the other variants before this, that were still causing us a huge problem.

Dr. Angie Rasmussen  24:02

I think that people would be a little more individually empowered to sort of process this information and apply these things to their life. Because right now, I mean, I’m just tired. And I’m sure both of you are as tired as everybody of this pandemic, like this is not fun for any of us. And I can’t think of how many times in the last month I’ve just thought to myself, I can’t wait to go out to dinner again in a restaurant. I can’t wait to go meet my friends for a drink.

Dr. Angie Rasmussen 

I think that a lot of people are at that place and we’re missing an opportunity by talking about oh my god, it’s more transmissible like we need. We need to do this and not the other thing. We need to do the same things that we should have been doing all along. And maybe now is a good opportunity to double down on those messages and ask people to be more vigilant and to really double check that they are implementing as many of these exposure reduction methods as possible.

Dr. Bob Wachter 

Paul, do you agree with that and maybe I’ll push you to be a little more specific now that we know that these variants are out there, and particularly the UK one, have you changed your behavior at all? Let’s say in the last month or two compared to what you were doing three or four months ago?

Dr. Paul Turner

Well, I guess I have to admit, I’ve been pretty, pretty good with adhering to the advice that the medical professionals are providing, since way back, I mean, I was definitely one of the first scientists that I knew was kind of canceling trips in February, thinking, “Hmm, this doesn’t look good” I should probably just stay home. And the advice that you just heard, I completely agree, this is a time when we need to double down and just do the things that we’ve been advised to do anyway. And try to use this as a motivational tool, create the narrative that now’s the time, you know, do everything that is being advised that would make you safe, and your family safe.

Dr. Paul Turner

So, I have to admit, I am not radically changing my behavior. I am still doing many of these things that we just heard listed by Dr. Rasmussen. Now, I guess one of the things I would toss in is okay, the places that I do go to which I must visit like the grocery store, you know, they are better setup. Now, right? They’re using techniques now, most of them. I can’t speak for all grocery stores in the United States, but the ones at least nearby to me here in New Haven. It’s quite obvious that they to keep their doors open and keep their employees safe. They’ve changed with that store it looks like. So in a way, this is part of what kind of as an infrastructure that is set up to help us but it is by no means the time to be going backwards and doing less of the behaviors that we’ve been advised to do.

Dr. Angie Rasmussen  26:49

I wear two masks anyway, when I go to the store.

Dr. Bob Wachter 

I do too. And I’ve had I’ve had one of my vaccine shots, I still do.

Dr. Paul Turner 

Excellent. I recommend that people do this if they choose to. So I think it’s do more of what we’ve been advised to do.

Dr. Bob Wachter 

And I should give credit to the questions about what to do and behavior came from Suzanne Unger and Chow Huang. And another question, Heather Beale asks, maybe this for Angie. “Is the truth of the strain is more contagious for children. And what do we know about that?”

Dr. Angie Rasmussen

So the question of children is really hard to wrap your mind around for these variants and for COVID, in general, because children are more likely to have asymptomatic infections, and therefore they’re less likely to be detected. So our data about prevalence in children is still actually pretty bad. There’s a lot of holes in it. You know, initially, there were reports from the UK that this strain was more capable of infecting children. And then since then, some data has come out to say that that’s not really true. That this is the same as any other variant of SARS Coronavirus-2 in that regard. So I think the message that people need to take home is your children, no matter what are susceptible to being infected with SARS Coronavirus-2.

Dr. Angie Rasmussen  28:11

Now, whether this variant makes them more susceptible or not, we don’t know. But even if not, like you can’t behave or think that children are going to completely escape this because they will not and even though children are more likely to have better clinical outcomes fortunately, if they do get infected, there are still those unlucky few children who do have very severe disease and in some cases have died. So I think that people should not be more alarmed about their children, but they should be taking the proper precautions to make sure that their children’s risk is minimized. And with regard to how this should affect schools. That’s a very difficult question. But I don’t think these variants really play a role in that.

Dr. Angie Rasmussen 

I think that schools really need to think about whether they’re open or not based on overall prevalence in the community. So if you have a lot of SARS Coronavirus-2 at some point, you’re going to get to the place where it’s not safe to have kids going to school, at the very least because they might get infected at school, bring it home and transmit it to other more vulnerable people in their households. And that’s true whether you have a high proportion of people with this variant in your community or not, at some point, if you have enough virus around, then it’s not going to be safe for any business to be open, much less schools.

Dr. Angie Rasmussen 

So I think I really wish that there were and I hope that one of the things that comes out of this pandemic is a better way to collect data from kids in particular, because I think this has really impacted the most people’s lives, especially those kids, you know, talk about a group of people who have really struggled to get through this pandemic. And it’s had ripple effects all the way, you know, through their parents and to society at large. I think that we’ve done ourselves a real disservice by not having a systematic way of collecting data from children on this issue.

Dr. Bob Wachter  30:26

Let’s turn to the South African variant and this question of is it now going to be likely to be somewhat resistant to the vaccine? That’s what Kate Whelan asked. So first of all, do we think it is going to be resistant to the vaccine? And then we’ll talk through if that’s true, what the implications of that are. So, Paul, do you want to start with it?

Dr. Paul Turner 

I’ll give it a shot. It’s probably more in Dr. Rasmussen’s wheelhouse. But, yeah, the difficult issue of do you have a variant that is showing some ability for less efficacy to be controlled by the vaccine, and this is definitely the big worry. Now, I haven’t worked on that variant. And I don’t know anybody personally, who’s done the studies. I’m sure they are being done in earnest right now, to figure this out as quickly as possible. I suppose I go back to what I said a little bit earlier that the fact that we have the successful rollout of the vaccines, and we know that the efficacy is quite good and protecting people from infection of the major variants that are circulating.

Dr. Paul Turner

You know, that’s excellent news. And the question is, how much would these new variants through time, counter that effort and push us back? Now, I’m not working directly on this strain. To me, it begs the question of what is the reduced efficacy mean, for the vaccine? Is it? If it’s zero, I would be extremely worried. If it is less than 50%, I would be still pretty worried, but actually don’t know what the estimate is. And I’m not sure. Maybe Dr. Rasmussen has actually seen some of the data. And could speak to that. But those are the results that I really want to know.

Dr. Bob Wachter  32:17

Yeah, so let’s hand that off to Angie. And also, as you Paul was mentioning, we’ve got a study it are those studies that are efficacy studies, we’re seeing if people get infected after they got the vaccine, are there more kind of biologic and theoretical studies that show the change in the structure of the spike protein, and we can guesstimate from that, that the vaccine is going to work less? Well?

Dr. Angie Rasmussen 

This is a really complicated question, will the vaccine work or not because of this one mutation. I think it’s pretty unlikely, given the way that the immune system works and the type of immunity that vaccines are eliciting that a single mutation will completely negate the vaccines efficacy, I think, though, you accumulate enough of those mutations, and you may have a problem. And the other thing is right now, we’ve only really looked systematically at the effect of these mutations that are in the receptor binding domain. And fortunately, that other mutation and N501Y, at least again, in cell culture experiments with serum doesn’t seem to have any effect at all on neutralization. So that’s great. But the reality is we still have a lot of work to do to try to determine that quantitatively.

Dr. Bob Wachter 

So we’re in the middle of the vaccine rollout. By all accounts, it’s not gone as well as anyone had hoped it’s been if anything sluggish, but let’s say we get it right, and we turn the ship around and start vaccinating people more efficiently. And we figure out the right protocol and stick with it. Does the prospect of these variants change the dynamics of the vaccines efficacy and the numbers we need for herd immunity? Let’s assume that at least the possibility that it does make the vaccine a little bit efficacious on some proportion of the infections? You know, there may be it’s not 95%, maybe it’s 80%. Who knows?

Dr. Bob Wachter  34:06

But how does that change the end game? If you know, on my most hopeful morning in November, when we heard about the Pfizer and the Moderna results, I said okay, by the summer we will reach 200 million people vaccinated and that’s 65% of the population. And we’ll be good to go. And we can all go back to you know, quote unquote,”normal.” Now, if these variants are entering our lives, how should we change our thinking about that?

Dr. Angie Rasmussen 

Well, if it’s less efficacious, that means we probably need to vaccinate more people to reach the herd immunity threshold. We already have data suggesting that 65% is below the herd immunity threshold in Manaus, Brazil, where the virus basically rip through the population. Virus still spreading effectively after 70% of the population had been infected, suggesting that the herd immunity threshold normally is higher than that. So I think that if the vaccines are a little bit less effective against these variants, that means that ultimately we’re going to need to vaccinate more people to achieve that herd immunity threshold.

Dr. Bob Wachter 

And do you think then what is likely to happen is that the companies will be rejiggering vaccines to be better at these, these new variants. And if I’ve already gotten my two shots, do I now get another two in the summer because they’ve come up with a new and improved vaccine?

Dr. Angie Rasmussen 

And this might be a question that I can turn back around and ask you, because I think that long term that companies are going to have to be prepared to do that, you know, we don’t have very good correlative protection right now for these vaccines. So unlike the influenza vaccine, which we do rejigger every year because we know what the correlates of protection are. And we have a system already for trying to predict which sometimes we don’t do very well.

Dr. Angie Rasmussen 

But fortunately, influence is a very different virus. We reformulate that vaccine every year without having to do extensive clinical trials. I’m very curious, if either of you know, like, what the process would be, in terms of adjusting the vaccines, because the mRNA vaccine platforms are actually technically quite easy to adjust. For me, the big question is, how long would it take to make that adjustment? From a regulatory standpoint?

Dr. Paul Turner  36:17

That’s a golden question. Yeah. I don’t know the exact answer. But that’s spot on. I mean, the fact that these new platforms should be more nimble, to adjust them faster, is very good news, right? If these types of mRNA and, you know, similar technology, vaccines can be done, you can make these changes more easily than that’s amazingly good. But we need a national plan. And it is a tragedy, if you have doses of vaccine that are being thrown out. I mean, it really is. So we need a coordinated national plan. And I do believe the new administration is much more behind that effort than the current one.

Dr. Paul Turner 

So I have reason for optimism. But what was also stated about the herd immunity effect, and how many people need to be vaccinated to achieve the success and pushing back the pandemic, and it might be quite high. And I’ve, at least thankfully, I’m seeing a greater willingness here in the US, I don’t know the numbers globally, that people seem to be more willing than not to be vaccinated. And this is important, if we’re going to get it under control, you have to believe that the science is going to work for you, you have to believe in science. And this is what we need.

Dr. Bob Wachter

Let me thank both of you for an incredibly thoughtful discussion. This is some scary stuff. And yet, we need to understand it, that’s really been the theme for the entire pandemic. It’s scary, but we have control, we can take actions, it’s much more important that we understand what the threat is. And as I think both of you said, the most important advice is to double down on the things we already know are the right things to do.

Dr. Bob Wachter

And to support the science and the scientists who are trying to understand this to do the testing and sequencing we need to do in order to not be flying blind. And I appreciate you educating me and educating our listeners so that we understand this better. So thank you so much, and stay safe, and really appreciate it.

Dr. Angie Rasmussen  38:18

Thanks for having us.

Dr. Paul Turner

Thanks for being on.

Dr. Bob Wachter 

A pleasure.

Dr. Bob Wachter

Well, that was a really powerful episode, I finished it, at some level, being a little more concerned about these variants, but also knowing more about what they mean. And kind of recognizing that if we keep doing the right things in terms of staying safe, that we will be safe. And that scientists like Angie and Paul are on top of it is quite reassuring. So thanks for joining us, we’ll have upcoming episodes. Several of them we’ve already planned one is on the extraordinary crisis in LA where things are really dire. And learn from people on the ground about what’s happening and why. And then we will have a toolkit that I think will really be pretty special, looking at the vaccine rollout, but really through two lenses.

Dr. Bob Wachter 

One is why it’s been so problematic. And it’s taking so long, but also looking at it through the lens of ethics, because there are a whole lot of ethical implications that we’re all talking about in terms of the prioritization and who goes first and who goes second. And it’s complex, not only as a logistical problem, but really as an ethical problem and we will cover all of that and we’ll have many more episodes as well. So look forward to having you join us. And until then stay safe and look forward to seeing you soon.

 CREDITS

We’re a production of Lemonada Media. Kryssy Pease and Alex McOwen produced our show. Our mix is by Ivan Kuraev. Jessica Cordova Kramer and Stephanie Wittels Wachs executive produced the show. Our theme was composed by Dan Molad and Oliver Hill and additional music by Ivan Kuraev. You can find out more about our show on social media at @InTheBubblePod. Until next time, stay safe and stay sane. Thanks so much for listening

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