The World Health Organization has recently commented that the pandemic will not end as the Omicron variant and that the high levels of infection seen around the world will likely lead to new variants as the virus mutates. But what can we expect from future COVID variants, and what will our lives look like in the coming months and years?
We spoke to Nicholas Timpson, professor of genetic epidemiology at The University of Bristol, to get the lowdown.
Is it inevitable that we will have future COVID variants?
You could draw a parallel to the seasonal flu, not in terms of gravity or scale or anything like that, but in terms of the appearance of variation. Flu vaccine is altered every year and it’s an effort to attend to the presence of novelty in the pathogen and to prime people before they get exposed to it.
I think in the case of COVID, as the public we’ve been exposed to the idea that there is variation. And it seems rather intimidating, doesn’t it? The thing that we thought we were familiar with is changing in front of us and the rules of engagement with that pathogen are not stable.
What’s really fascinating about COVID is that our best efforts to mitigate the disease, the products of SARS-CoV-2, changes the game for the virus. It adds complexity to this story because we are keeping selection pressure on that virus, which is doing its best to survive. And, as we know, can replicate and be variable very quickly.
Now we’ve got this very large-scale event where lots of people with lots of copies of virus are around and on top of that we suppress [the virus] with great weight, either by controlling the population or by vaccine. The combination of these events, in my mind, leads to the inevitability of the emergence of new variation.
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Is there any way that we could predict the emergence of certain variants?
It might be prudent to rephrase that. So the material that selection is acting on to generate new variants arrives because of chance events, which are not predictable. Mutations will happen in a manner that is totally unpredictable. Their arrangement to generate a new variant is governed by the pressures acting on the virus externally.
So take lockdowns, for example, if you make it difficult for a virus to transmit between people by putting people in their homes nothing might happen. But equally, if a variant appears by chance alone that is more transmissible that will be the variant that gets elevated in frequency because the current pressure is that it’s hard to transmit because everybody’s at home.
The arrangement of the mutations and the variation is non-stochastic [not random] – it’s definitely ordered, but the appearance of them is completely random. So it’s random mutations ordered by the pressures that we put on the virus.
Prediction is not just getting a crystal ball and saying we’re going to get a variant that will do this, but we do know that it’s likely that if we’re locking down hard then the only variants that are going to emerge are the ones that are good at being transmissible. So that’s what I mean by prediction. If there is a vast amount of virus kicking around and people are carrying virus, which is reproducing quickly and holding it, the simple probability of getting mutations is inflated.
And then, of course, the likelihood of events being transmitted as a result of that or appearing in multiple places, which something called convergent evolution, is heightened. If everybody’s locking down around the world it would be of no surprise to see a hyper-transmissible variant appear in London and in Africa and in Australia, quite independent of each other. But that’s because the pressures are the same.
Which is why the really clever guys at the Sanger Institute and various other places are so good at being able to look at this. A variant emerges, they sequence it and say, ‘Right, we’ve got spike mutations. We’ve got x y z’. Those are things that we know lie in domains which would be important for the evasion of vaccine or the variant being more transmissible.
This happened, and it spread with incredible speed with Omicron. It was almost like the recipe of what this is going to be like was told after the first one was sequenced. It was like, ‘Well, this one looks like it’s going to evade a bit. We don’t know about how bad the disease is, but it looks like it’s going to be transmissible and move fast’. And surprise, surprise, off it went.
So there’s two bits to prediction, really. But it’s about the pressures we put on the virus rather than predicting what variants are going to come next because it’s chance events ordered by selection. That’s the first point. And the second point is that it could be that we see nothing for 10 years. It could be we see something tomorrow. But the probability of those events is changed by the magnitude of the pandemic. So if there’s a lot of virus we’re just likely to see more variants than if there’s less virus.
How does one variant emerge as the dominant variant?
A simple way to maybe think about it is to consider that you’re dealing with is population dynamics. There is a niche which can be occupied by SARS-CoV-2. And these population dynamics tend to be occupied by one or a few strains. If the events that lead to getting a COVID infection are essentially being replaced by a variant that is more transmissible and is better at sneaking around the things that we’re trying to do to avoid it, then that niche will become occupied by the new variant to the cost of the presence of the other one.
You’ll always get different variants. In fact, one really interesting thing was the dynamics of infection just before Christmas when you had one in 20 or so kids at school, at primary age, with COVID, mainly Delta. Then you also had the 65 plus people with predominantly Delta who were keeping themselves to themselves.
So, then you’ve got this explosion between sort of 18 and 45, something like that, where you’ve got Omicron going wild. At that moment in time you had this situation where you had some dominants some not dominants and then this dynamic shifting across the population. It’s about niche occupation and the properties of one variant to become more frequent in that niche as a result of its ability to be more transmissible.
Are there any trends that we can look out for?
Getting to a situation where there’s just less virus kicking about is a good thing because that would then reduce the chances of those events happening. A trend which would be interesting to look at would be the relationship between the frequency of emergence of these variants, which have a big effect on our lives, and just how much virus there is. There’s two parts to the story but we must vaccinate the world. One is equity, which is the big push. And that really belies the second part of the vaccine story, which is you don’t really get vaccinated to avoid infection, you get vaccinated to avoid being a burden on healthcare. So that’s one part of it.
The other part of it is being able to stand in the way of the virus before those chance events happen. We need to reduce the frequency of those events and then lighten the load of the pandemic. I think those two things are important. That’s the big message, isn’t it if we can get to that stage, that’s excellent. But I think the truth of the matter is we’ll probably see something which is a more of a mixture.
Looking down the line, most of us and our children will have been exposed to COVID, either via vaccination or via wild infection, multiple times and in different flavours within the next few years. And that will be the recipe which probably turns COVID-19 more into the cold/flu type situation that we’ve been talking about for ages. The variants will become less novel and we’ll be more primed for seeing it because actually there are parts of the virus which don’t change very often at all.
So if you’ve seen a wild infection you will have a broader immune response than somebody who’s just been vaccinated. So the best place to be is probably somebody who’s been infected and vaccinated because you’ve got a broad immune response. And if that’s happened to you two or three times, the gravity of the disease will go down and down.
Is this what people mean when they say we will have to learn to live with the virus?
Yes, I think so. It’s not saying we’re just going to have to get used to people dying. It’s quite the opposite. It’s saying we’re going to have to be in a situation whereby we’re educated to the gravity of the disease at the time and the burden on our ability to care for people with that disease.
So yes, in the future, it could well be that you can go to work with COVID, but you just put a face mask on. And that’s fine because the disease is having less of an effect on people. And we’re able to manage things. The counter to that would be that the disease is still bad and we just have to go through periods of isolation.
What’s the balance between best- and worst-case scenarios in the next couple of years at this point?
We become a bit hypothetical when you go to that kind of question, but of course, it’s what everybody’s thinking about, and it would be churlish to say that we don’t want to know about that. Your best-case scenario is this notion of living with a new virus – through the combination of behaviour, prospective intervention vaccinations, and responsive interventions like treatments for the disease.
What I think what it comes down to is a bit of luck with the fact that the virus pretty much behaves as it is doing now. It may well be a situation where endemicity becomes a genuine thing and everybody has seen a mixture of flavours of SARS-CoV-2. And because of that, if you either get it or it’s a relatively high level seasonally, the relative impact on society is lessened. That’s good end that we all hope for.
Evolution is a bad word because evolution implies progression, which is not the case. What happens is random change, which is then ordered by selection pressure. So therein lies the problem, because Omicron is more transmissible and it’s been a bit of a nightmare, but it appears to be a bit milder than the others. But I’m afraid to say that that was luck. The next mutation, which happens to be coupled with increased transmission and potentially scary things like escaping vaccine, isn’t a guaranteed less virulent version of COVID.
At the other end of the spectrum would be the arrival of Omicron Plus Plus, which is all of the things that Omicron was, but nasty. That’s a pretty bleak way of thinking, and we have to hope that the frequency of mutations go down and we all get exposed to it a bit more often and the gravity of disease goes down. That’s the way forward.
And historically, I guess that’s what we’ve seen with other exposures of a similar nature. The softer side of this story is that everybody’s pretty tired and I think we need a good news message here, which is exposure in the community and COVID being endemic. These are good moves that are going to help us.
About our expert, Prof Nicholas Timpson
Nicholas is a professor of genetic epidemiololy at Bristol Medical School.
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