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Take Note: Infectious disease expert Andrew Read on why omicron doesn't mean COVID-19 is evolving to be less severe

Andrew Read in his office at Penn State
Min Xian
Andrew Read, director of the Huck Institutes of the Life Sciences at Penn State, talked with WPSU about omicron's surprising transmissibility and why predicting how viruses evolve is difficult.

Researchers are studying the omicron variant: how transmissible it is, how sick it could make those infected and what this variant tells us, if anything, about how COVID-19 is evolving.

Andrew Read, director of the Huck Institutes of the Life Sciences at Penn State, talked with WPSU's Min Xian about the unpredictability of virus evolution.

Here's the conversation:

Min Xian: Welcome to Take Note on WPSU. I’m Min Xian. The emergence of the omicron variant has prompted the latest wave of COVID-19 cases in the U.S. and across countries including France and Britain. Researchers are racing to learn more about this variant. Andrew Read has been following the latest research and data closely. Read is the director of the Huck Institutes of the Life Sciences at Penn State and studies the ecology and evolution of infectious disease. He says how viruses evolve can be a lot like rolling the dice.

Andrew Read, welcome to Take Note.

Andrew Read: Thanks for having me.

Min Xian: After omicron was first discovered last November in South Africa, its genetic sequence showed 30 mutations in the spike protein, compared to the original Wuhan strain. What's the significance of that?

Andrew Read: Well, the spike protein is the part of the virus that's used to get into human cells. It's also recognized by human antibodies. So the very big differences between omicron and what had come before in the spike protein were of concern, from the point of view of the antibodies. Would the antibodies that were raised by vaccines or natural immunity work as well against that very mutated form of the spike protein?

Min Xian: And does that have any kind of effect on how transmissible the variant could be?

Andrew Read: Yeah, absolutely, though, that is very hard to predict in advance. The mutations that affect the spike protein affect the ability of the virus to get into cells. And so mutated forms could be less effective at getting in. And so they would not replicate as well in our body. Or they could get around antibodies more effectively, and so replicate better in an immunized body. So it can go both ways. And the concern, of course, with omicron was that it seemed to have come out of nowhere with all of these mutations and then spread extremely quickly in South Africa.

Min Xian: And so far, what do we know from research about omicron’s transmissibility?

Andrew Read: Well, we know because it spreads so quickly that it is extremely transmissible. The exact reasons for that is still somewhat mysterious, it does seem to spread from person to person a bit faster than – so the shorter incubation periods seem to do very well inside people it does get into, in terms of replication, and so forth. So the tricks that uses are probably a combination of the ability to get around immunity that's been generated by vaccines, or by natural infection, as well as this still slightly mysterious ability to replicate, to move from person to person, a bit quicker than the previous variants.

Min Xian: And what do we know at this point about how omicron replicates itself and how it causes diseases in humans? I've read that the location in the human body it affects differs from previous variants.

Andrew Read: That's right, the data seem to be accumulating that show that it's very good at replicating in the upper respiratory tract and not so good at replicating in the lungs. And that's probably tied up with the explanation for why it seems to cause less severe disease in any particular infected person.

So transmissibility is critical in all of this. We know any variant that's more transmissible will spread and take over the world – more transmissible than any ancestor – will spread and take over. So the transmission, the transmission effectiveness, is really key in how things evolve here. So any future variants are going to be more transmissible in the world they find themselves in.

So the world that future variants will find themselves in is a world that is now increasingly vaccinated and increasingly exposed to omicron. So immunity to omicron and vaccination are going to dominate at least in many parts of the world. And so any future variants have to be more transmissible in that world, than their predecessors would be in that world. And that is the very difficult issue to predict. Will that be true or not? I think on balance likely that there will be more transmissible, but what would they be like? What will they be more – just cause more severe disease? Will they get around to vaccines? That's the hard part to predict.

Min Xian: Sure, and let me know if this question makes sense. What are the relations among these variants? For example, right now we're hearing the delta variant is still around and of course, we have omicron. Do they compete with each other?

Andrew Read: Yeah, the question makes sense. It is a little bit unclear what causes some variants to go down while others come up? Well, we know why they come up – it’s they're much more transmissible, why that's associated with other variants going down isn't completely understood.

So omicron is spreading faster than delta. So that alone will mean that it's going to take over the world. But that doesn't explain why delta has got rarer. And it might be that delta has got rarer because more and more people have seen omicron and an immunity to omicron seems to give protection, some level of protection against delta. So it could be that. It could also be that people start to engage in, you know, social distancing, mask wearing and so forth when a new variant is around. And that slows the transmission of a new variant, but also slows the transmission of the old variant.

The competition term itself, strictly speaking, would be competition for susceptible hosts. And so a host who's vulnerable to both delta and omicron, omicron will get there first, because it transmits faster, and if that infection with omicron, then means delta can't get into that person, then it's going to have an advantage and omicron will go down. And that would be what competition would look like. We're not really sure if that's actually what's going on at the moment.

Min Xian: Previous variants of SARS-CoV-2 followed a path of increasing levels of transmission, and increasing severity in illness that they cause. Omicron appears different in that, although it is more transmissible than delta. So far, it's not making people as sick. So that prompted a lot of speculation about whether it's becoming a trend that the virus will continue to become less severe. What do you say about that?

Andrew Read: Well, first off, let's hope that's the case. But there isn't anything in theory or experience in other viruses to say that the inevitability is towards less and less virulent variants.

We had this very good data that alpha was more virulent than its predecessor, and delta was more virulent than alpha. And so we've had two steps up. And then omicron now seems to be causing less severe disease. So that's a sort of step down in virulence. The next one could go in either direction. And there's really no way to know that.

The only thing we can say with certainty is that the next variant will be more transmissible in the new world of vaccinated and immunized people, than were the previous variants. Otherwise, the previous variants will just come back and spread. So if there's a new variant, it's got to have an advantage in this new world. So it really could go both ways. And let me give you a couple of scenarios on that.

One way it could become even less severe, would be a variant that doesn't make anybody sick, won't lead to people self-isolating, and quarantining and staying home from work and so forth. So it will have an advantage because people will be out there moving around, not knowing they have it. So that sort of variant would have an advantage. And if it was completely silent, we didn't notice at all, then it would just be able to get on with its business without any interference from us.

On the other hand, it could be that variant that can make you cough, for instance, would have a transmission advantage. And so it might be that the next variant causes more symptoms like that, and more transmission, and even though at some point people would start to stay home, in the interim, they've been coughing and spluttering and spreading it around. It could also be that a variant that is able to suppress the immune response would spread very much more efficiently, much faster. And suppressing immune response can be associated with more severe disease. So you could imagine it going both ways. And there really is absolutely nothing in theory or in experience in other viruses that allows us to make confident predictions about that. And there are other well studied viruses, which have become more severe through time. It's not inevitable that things become less severe with time.

Min Xian: We just don't know until it shows up.

Andrew Read: That's right. Predicting the future of evolution is extremely difficult, very, very difficult. And until we really see what's going – what's happening next, we won't know. Now it's possible that a variant that comes along next that is spreading in a world that is almost everybody's seen omicron that the immune levels in that population and the immunity coming from vaccination will mean that not very many people are sick. But that doesn't say anything about the intrinsic disease severity of the next variant. And it might be that it's nastier, or it's nicer.

But I want to emphasize that the world is a very different place from where it was when we first got the virus. Now, we have large amounts of immunity in the populations either naturally from infection or from vaccination, especially with boosts. And that is substantially reducing the disease severity of the infections we've seen so far, that seems likely to continue.

The nightmare scenario was that we get a variant that transmits very effectively. But it is causing severe disease, like we had to start with, it's getting around to our immunity, not just infecting people, but also causing severe disease in people. And something like that came along would be kind of like a new virus altogether, there'd be no protection from the past. And that really could be very unfortunate. I’ll have to say, I think it's unlikely that would happen with SARS-CoV-2, with the COVID-19 virus, it seems unlikely to me that it could spawn a new virus that's so different, that there wouldn't be any protection from the vaccines or from natural infection. But we could get another spillover, you know, COVID 24, COVID 26, that could be different enough that it would be as if it was a new virus.

Min Xian: A critical factor in how viruses evolve is the environment that they are in. So there is an incredibly complicated set of environments where SARS-CoV-2 can mutate right now, through people vaccinated, unvaccinated, boostered, with natural immunity, with suppressed immune system, and also we have seen through animals as well. What does the research say about how these different hosts can affect the path of evolution of the virus so far?

Andrew Read: Yeah, to your list of differences, I would also add that the world is using very different vaccines in very different places. So in the States, we tend to be thinking about mRNA vaccines. But there are protein based vaccines being used in China, for example. And in fact, most of the world has been vaccinated with different sorts of vaccines from those being used in the US. And that seems likely to continue that most of the world will be vaccinated with very different types of vaccines.

Yeah, so we have all of that sort of heterogeneity going on, differences between people in their immune experience and their immune protection. And that means that from the virus's point of view, the world has got a lot of variation in it. And so it's going to be in any single person it gets into, it's going to be evolving, that's inevitable, and then it transmits to the next person. And it's going to be evolving there. And that process is going to differ for different viruses in different places in the world.

So somewhere, it could go from a susceptible person to an immune person to somebody who's immunosuppressed. And so that is going to create different pressures for each of the different lineages of the evolutionary tree. And we don't know at the moment whether those differences will result in a highly diverse viral infection. So around the world, we'll have various – all sorts of different variants. And they'll be coming and going and changing and swapping out and we'll have to use different vaccines at different places, or whether in fact, a single variant will come to dominate, like we seem to be seeing with omicron now. We just can't say at the moment.

In agricultural settings with other coronaviruses, for example, in the poultry industry, we see situations where different variants exist in different places and at different times. The actual choice of vaccine can vary through time depending on the variant you have in your area. And so there's a diversity of variants around the world. And there's a diversity of vaccines.

Min Xian: We talked about the amount of mutations that were identified in omicron. Has there been any work done to trace where omicron comes from based on those mutations? And what do we know about how omicron came into being right now?

Andrew Read: There's been a lot of work trying to trace where those mutations came from. And there's a lot of mystery. Omicron came more or less fully formed out of the virus tree and it came out many months ago, and we don't know where it was lurking. And it could have been, for example, an animal population or a chronically infected person, an immunosuppressed person had the virus for a long time. Yeah, the origins are mysterious and I think likely to remain mysterious until we see more of these sorts of things and get a picture of where they come from.

Min Xian: If you're just joining us, we're talking with Andrew Read, director of the Huck Institutes of the Life Sciences at Penn State, about what the omicron Varian tells us, if anything, about how the COVID-19 pandemic might be evolving.

There's a new and not yet peer reviewed study published earlier this month, where researchers looked at data of nearly half a million people in the Canadian province, Ontario. The study found that two doses of COVID-19 vaccines, and those are mostly mRNA vaccines, are unlikely to protect against infection by omicron. And the third dose provides some protection in the immediate term, but substantially less than against delta, effectively saying that omicron can beat the current vaccines we have. Was that surprising?

Andrew Read: Yeah, I was really shocked when I saw those data. I did not expect that we could get a variant so fast that would be so effective at getting into vaccinated people.

We have to be clear here what we mean, though, because the vaccines – and that study is consistent with – the vaccines are doing a very good job of protecting against severe disease and death. And of course, that's what we really care about, from the health of the human population, of course.

But the transmission is what drives the evolution of this virus. And what the Ontario study showed was that the vaccines had no impact on reducing the chances of getting infected in the first place. So if you were vaccinated with two shots of the RNA vaccines, omicron could infect you as if you had never had those vaccines. So it protected you from getting severely sick, but it stopped getting infected in the first place. And that to me was staggering. And then the boosts showed – that study shows that the boosts maybe get you a third of the cases, 30% protection, which means that one in three times you get exposed to omicron you wouldn't get infected, but the other two times you would. So even a well boosted person can get infected with omicron. And to me, it was really amazing that we could get so fast, a variant, that from its perspective, doesn't see the difference between a vaccinated and unvaccinated person.

Min Xian: There are two interesting caveats from that study I want to mention. First is that in Canada, the policy is that if you are fully vaccinated, you're more – you have more freedom to get around, attend venues, go to events, and that could potentially impact the transmission and the infection of the people. And so I think that is an interesting, important thing to keep in mind when we're looking at these data that they do get influenced by policies.

Andrew Read: Yeah, absolutely. Human behavior affects a lot of these things. So in that particular case, actually, there was – people that have been vaccinated with two doses, hadn't had been boosted, but had the two doses of walbeck, those people are actually more likely to get infected. And the likely explanation of that is those are the only ones the Canadian government is allowing to go to restaurants and concerts and those sorts of things. So people who are vaccinated are engaging in riskier behavior. They've obviously quite different in the US where there aren't those sorts of restrictions on who does what.

The other thing that's amazing to me about that study is they've almost got nobody in that study – there's a few thousand people, but decreasing numbers of people in that study that you can use to compare the vaccine efficacy against unvaccinated people. There's almost nobody unvaccinated in Ontario now. And among those that ever, some of them probably had COVID. So actually finding the comparison group is going to be increasingly difficult going forward, and we probably won't be talking about vaccine efficacy, we'll be talking about how well a vaccine protects against, you know, omicron compared to delta, rather than omicron versus no vaccine at all.

Min Xian: That's the other interesting caveat that I was going to mention. And so does that mean, we need both new tests and new vaccines, because we're now dealing with this variant that seems to be very good at getting around, at least the protection from the vaccine against infection and transmission?

Andrew Read: Yes, I think that the testing is all about trying to control transmission. And you know, that's the name of the game, do I have COVID, can I go see grandma, sort of thing? That's critical at any point we need to be able to do testing and understand what we have and what the risks are and so forth.

In terms of do we need new vaccines? Well, from the point of view of the majority of us, the current vaccines are good enough at protecting – very good at protecting against severe disease. And so they are very, very good vaccines from that perspective.

The fact that omicron seems to be able to infect people who are very well vaccinated and transmit on from people who are very well vaccinated means that people who don't, can't get vaccinated or have some sort of, you know, immunosuppression issues, those people are at risk of getting something like omicron from vaccinated people.

So there is no protection of other people, or very little protection of other people, coming from getting vaccinated. So if you get vaccinated, it makes good sense because you're better off, you're protected against severe disease, but it looks like you will still be likely to get infected and pass it on to others. So if those others are unable to get vaccinated or immunosuppressed or whatever, then they will be at risk.

And to me that is – that's a very sobering observation that the one of the terrific benefits of vaccination in other settings has been that when you get vaccinated, you protect yourself against severe disease, like we get here, but you also protect others against the likelihood of getting it from you. And that seems not to be substantially the case with omicron.

Min Xian: What would happen to the idea, the concept of herd immunity, if at some point our population would have immunity either from vaccination or infection?

Andrew Read: I think the concept of herd immunity doesn't apply anymore. At least with omicron, and probably with delta variants.

Herd immunity is the notion that vaccinated people are less likely to get infected and less likely to transmit it on. And so that means unvaccinated people get protected by other people getting vaccinated because they're less likely to get it. That seems not to be the case with omicron and probably delta either, that we can't get good enough protection against infection from the current vaccines to stop infection transmitting from vaccinated person on, and that means we can't get herd immunity with the current vaccines and the current variants.

Min Xian: And I think that reminds me of the point that you make earlier, which is that right now perhaps it is more practical to look at what the protection vaccine provides in terms of how much it protects people from severe illness and death rather than just, for example, looking at case numbers, because that will probably tend to just keep ballooning.

Andrew Read: Yeah, I'm actually less and less interested in case numbers. All that matters is the disease severity, with the current generation of vaccines and the current variants, and the way to think about it, in my head at least is that there's two things that come from vaccination, one is that you are less likely to get severely sick yourself. The other one is that you are less likely ending up at a hospital and take a hospital bed from somebody else. So the community is protected by you getting vaccinated, but it's via the hospital system. It's not the fact that you are less likely to infect somebody else.

And I think there's a strong communal argument that is good for the community if you get vaccinated, because it'll keep the healthcare system functioning better. It keeps unnecessary cases out of the hospital. But the herd immunity itself, that's no longer a deal when we have this level of breakthrough vaccination.

Min Xian: The term endemic has been mentioned more and more since the emergence of omicron. My sense is that when people ask whether COVID-19 is becoming endemic, they want to know whether it's becoming more like the flu or a seasonal cold, something that they don't have to worry too much about, which is not exactly what endemic means. Can you set the record straight about this concept for us?

Andrew Read: Yeah, to an epidemiologist, endemic means that it's circulating in an area without dying out and being reintroduced from outside. And usually, we mean that it's circulating at pretty steady levels as well. So it's not doing boom bust dynamics.

But the term is vague when it's used in the public domain. And I think in the case of COVID most people are thinking endemic is when can we get on with our lives and not have to worry about, you know, any of the complexities that go with what vaccine next and masking and, you know, when's it just going to become no big deal? Like, well, the flu is not exactly no big deal, but like a cold or something? I think that's what most people are thinking.

Min Xian: If we are talking about this idea of endemic or the idea of what is an endgame per se for a pandemic? When do we get to the point? What does it look like when we can say this is or we're near the end of the pandemic?

Andrew Read: I do think it's fair to think about a pandemic endgame. There isn't going to be an endgame for SARS-CoV-2. It is with humanity now, and it's going to be with us forever. It's not going to die out, it's not going to be extinguished. It's with us forever.

But the pandemic part of it, we have these enormous booms of infected cases with new variants. That could continue for quite some time. I really hope omicron is the last one. And it might be. But there seems likely to me there'll be other variants come along that are very effective at transmitting through immunized populations. But each one of these waves is going to be, if we're lucky, better than the last one, because more and more people will have immunity which protects them against severe disease.

So one of the, you know, blessings in disguise with omicron is that it’s transmissible so many people have had omicron and will by the time it's done, that the population is being immunized by vaccination, but is also being immunized by omicron. And so that means most people going forward will have a level of immunity that they did not have before omicron. And, you know, that's good news, because that means most people will be, at least against severe disease, have some protection from future variants. And that's much better than where we were.

It's not good news for the people who can't mount a good immune response, immunosuppressed people, and there's always a substantial minority of such folk in a community. So for those people, I do think that the variants of the future are going to remain a very significant concern, just like they are with flu, people who are immunosuppressed, the elderly, and so forth, it's a very significant concern when new variants come along.

But for the majority of us who are mounting good responses, it seems likely to me that we will, over the course of time, be less and less affected by subsequent waves. And we can imagine a situation where even if the variant that comes along next causes more severe disease in an unvaccinated person, the vaccination and the natural immunity will still reduce the severity of disease on average across the population. And so we'll still be better off.

But, you know, understanding what the next variant is like is – it's really a guess, at this point. And I'm optimistic, and we should definitely be optimistic that this is going to get better and better through time. But I do think we need to avoid complacency and we need to plan for the possibility that there will be variants that come along that are more transmissible than omicron, and cause more severe disease, they're easy to imagine. And it's very hard to know whether or not the virus can find them in evolutionary time, you know, in the next few months or a few years.

Min Xian: I'm interested to hear what you're looking at any kind of new data about the understanding of omicron, or just in general or what are you thinking about the next step, if we're not thinking about the end game, the next step in the pandemic, where we are right now, what are some data points, some research that you're paying attention to?

Andrew Read: Obviously, any new variant that comes along, we're paying extremely close attention to its transmission and its transmissibility properties, how it's transmitting, and whether it's getting through vaccinated individuals, and if so, how, and whether it's causing more severe disease or less severe disease. So future variants, those are, in my head, the number one questions.

At the moment, what I'm spending a lot of time doing is looking at the fantastic data that's appearing, you know, every week we get better and better data, on the transmission of omicron, through vaccinated people, through boosted people, through people have seen natural immunity, looking to see the impact of immunization, natural or vaccination, on the transmission of omicron. As in evolutionary biology transmission is what it’s all about. Are there signs that omicron has particular transmission advantages? And how are those impacted by, for example, human behavior? That's what I'm really fascinated by at the moment.

And part of that is trying to imagine if we did get a variant that came along that would cause more severe disease, would it be able to spread? How would it spread? What sort of variant might have an advantage in such a world and I'm particularly interested in the case where, you know, vaccination makes people less sick. That's the point of it, and it's really effective at it. Does that mean that variants that would have otherwise not spread are now able to spread silently through a vaccinated population? And are variants of the future going to be able to spread in these now very immunized populations. And those ones could be new variants of sorts we haven't seen before, you know, alpha and delta arose essentially in susceptible populations. Now, everything that's around is doing its work in immunized populations. And to me that's a fascinating question about the future.

Min Xian: Andrew Read, thank you so much for joining us on Take Note.

Andrew Read: My pleasure.

Min Xian: Andrew Read is the director of the Huck Institutes of the Life Sciences at Penn State and studies the ecology and evolution of infectious disease. He talks with us about the latest findings of the omicron variant and why it's so difficult to predict how viruses evolve.

You can listen to more Take Note interviews on note. I'm Min Xian, WPSU.

Min Xian reported at WPSU from 2016-2022.
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