COVID-19: What is the future of variants after Omicron?

The World Health Organization has recently commented that thepandemic will not end with the Omicron variantand 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 toNicholas Timpson, professor of genetic epidemiology at The University of Bristol, to get the lowdown from an population health science point of view.

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, but in terms of the appearance of variation. Flu vaccine is altered regularly 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 SARS-CoV-2, as the public we’ve been exposed to the idea that there is variation. And it seems rather intimidating? The pathogen 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 fascinating about COVID-19 is that our best efforts to avoid the disease, the product of SARS-CoV-2 infection, change 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 byvaccine. 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. The material that selection is acting on to generate new variants – mutations – arrive because of chance events, which are not predictable. Their arrangement to generate a new variant is governed by the pressures acting on the virus externally. To take lockdowns, for example, if you make it difficult for a virus to transmit between people by encouraging them to remain at home, but a variant appears by chance that is more transmissible, then it will be this variant that is elevated in frequency because it is the one able to evade current pressures trying to reduce transmission.

Prediction is therefore not just getting a crystal ball and saying we’re going to get a variant that will be of a certain type, it is more complex and unknown. However, we are aware that the nature of mitigation can act to shape the types of variants that are likely to emerge. Furthermore, if there is a vast amount of virus circulating and people are carrying virus, which is reproducing quickly, the simple probability of getting mutations is inflated.

And, of course, there is nothing stopping variants of apparently shared origin appearing in multiple places, which something called convergent evolution. If everybody’s locking down around the world it would be of no surprise to see hyper-transmissible variants appear in London and in Africa and in Australia, quite independent of each other. But that’s because the pressures are the same.

This context is why those at the Sanger Institute and other centres of genetics expertise do such important work tracking the arrival and emergence of new variant forms. As a variant emerges, they are able to sequence it and characterise the mutations defining that sub-type. This can then lend to sensible assessments of whether mutations might be important for the evasion of vaccine or the variant being more transmissible.

So there are two bits to prediction that we can perhaps comment on. Firstly that concerning 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. Secondly, a chance element, that it could be that we see nothing for some time or something sooner, but the probability of those events is changed by the magnitude of the pandemic at any given time.

How does one variant emerge as the dominant variant?

One way to think about this is to consider that you’re dealing with population dynamics – how different populations grow, contract and interact. There is a niche which can be occupied by SARS-CoV-2 and if the current variant occupying that spot is replaced by a variant that is more transmissible and better at avoiding mitigation against it, then that niche will be taken over by the new variant – becoming the more frequent infection type.

A really interesting illustration of this dynamy in variants and frequencies can be seen in the case of Omicron. Before Christmas primary age children were presenting with COVID-19 at high levels and this was predominantly the Delta variant. Similar patterns were seen at older ages. However, there was a rapidly growing number of Omicron infections in the middle age group – indeed making it difficult to assess the clinical gravity of infection in those early Omicron days. At that moment in time there was a situation where there was a shifting pattern 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.

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Are there any trends that we can look out for?

Getting to a situation where there’s just less virus in the population is a good thing because that would theoretically reduce the chances of new variant 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 circulating. With this, there will then be the events that influence these relationships. Part of this will be equity in the provision of vaccination, which is important in relating not only virus suppression, but also to the key message that vaccination is the route to avoiding serious disease and hence further unnecessary difficulties for healthcare.

Looking down the line, most of us will have been exposed to SARS-CoV-2, hopefully via vaccination, but possibly via wild infection – multiple times and in different flavours within the next few years. And that will be this recipe which may well lead to COVID-19 appearing as more of the type of cold/flu type situation that has been talked about for some time. The virus (overall) will become less novel and we’ll be more primed for responding to it. If you’ve seen a wild infection you will have a broader immune response than somebody who’s just been vaccinated. So, whilst vaccination is the first thing to do, it is true that the those who have been infected and vaccinated will have a broad immune response. In time, this may happen to us many times and the gravity of the disease may go 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 being seriously ill and 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 may be that isolation rules change and it is possible to be cautious rather than contained – and that’s fine because the disease is having less of an effect on people – however, this is clearly not there yet and we still face the possibility of a counter to that where the disease is still bad and we just have manage the situation accordingly.

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. The likely 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 it may come down to is partly luck with – potentially – with the virus pretty much behaving as it is doing now. There could be a situation where endemicity becomes genuine and essentially everybody has seen a mixture of “flavours” of SARS-CoV-2 and because of that, the relative impact on society may be lessened and a form of equilibrium reached. That could be the good end that we all hope for.

However it may not work like that for the reasons mentioned above – evolution is not progression, but ordered random change. Omicron is more transmissible and has generated a substantial wave of infection, but it appears to be milder than the other variants. Other mutations, however, could couple increased transmission with vaccine escape or worse disease, there isn’t a guarantee of lessening severity with versions of SARS-CoV-2.

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 then often the gravity of disease goes down as well. Indeed, the softer side of this story is that everybody’s pretty tired and I think we need a good news message here, which is the extraordinary development and role of vaccines, the endless work of our health providers and the growing level of exposure in the community and COVID being endemic. These are good moves that seem likely to be going to help us.