We’re three years into the COVID-19 pandemic. What might the virus do next?

As a world leader on virus evolution, Eddie Holmes wasn’t surprised when COVID-19 first appeared.

Like many who study the rise of infectious diseases, Professor Holmes believes SARS-CoV-2 was an accident waiting to happen.

But in the years since he became one of the first people in the world to publicly share the SARS-CoV-2 genome, much of the way the virus has evolved has surprised him.

“The level to which it has become more contagious is something I would never have predicted,” said Professor Holmes, a virologist at the University of Sydney.

This week marks three years since the World Health Organization declared COVID-19 a global public health emergency.

In that time, the virus has spawned five variants of concern, each more transmissible or more potent than the last.

Professor Eddie Holmes studies the evolution of viruses, including how they jump from one species to another. (The University of Sydney: Louise Cooper)

Originating in late 2021, Omicron has since splintered into hundreds of subvariants – amounting to what has been described as a “variant soup” – and will likely continue to splinter into more.

“The virus still has the ability to evolve and it will evolve … there is no evolutionary dead end,” Professor Holmes said.

“We will certainly see more immune escape variants … but when, where and what they will be is very difficult to say.”

Splinter virus reflects ‘immunologically complex’ population

While Omicron still dominates globally, the current spread of SARS-CoV-2 looks different depending on where you are.

“We see this complicated global picture of different places having different immune profiles given their history of infection and vaccination,” Professor Holmes said.

“This is very different from what happened in 2020 and 2021, when basically nobody was infected, so the virus kind of had free rein.”

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Earlier in the pandemic, the same variants tended to appear everywhere because everyone was in the same position: immunologically “naïve”.

Nowadays, against a background of diverse immune profiles and waning immunity, hundreds of Omicron subvariants have emerged as a result of geographically unique evolutionary pressures.

“That’s why we see this variant ‘soup’ of events, because they all come from different populations,” Professor Holmes said.

“It makes predictions [about the virus] even more difficult because the world population is now so immunologically complex.”

Australia has its own “unique” Omicron strain, according to virologist Stuart Turville, which is currently dominated by two subvariants: BR.2.1 and XBF.

In recent months, the emergence of new, more immune-evasive subvariants has caused a large wave of infections and reinfections.

Dr Turville, of the Kirby Institute, said although the subvariants in circulation were genetically “very diverse”, there was no evidence to suggest that any caused more serious disease.

“In the context of how they enter our bodies and how they grow in our bodies, all the Omicrons are quite similar,” said Dr Turville, whose team is studying the spread of SARS-CoV-2 in Australia.

But health experts have warned that it is still worth trying to avoid any new infection to reduce the risk of prolonged COVID, and for vulnerable individuals, the possibility of serious illness.

The risk of introducing new variants

Globally, COVID infections and deaths have increased since early December, including in the United States, where the highly contagious XBB.1.5 subvariant — unofficially dubbed “Kraken” — quickly overtook the rest.

“A lot of people are talking about XBB.1.5 because it has a fitness advantage, in that it can bind to its primary receptor – ACE2 – with greater affinity, and in addition it is very adept at navigating antibody responses,” Dr Turville said.

But the strength of a subvariant in one country does not necessarily mean that it will have the same advantage in another.

So far, only a small number of XBB.1.5 cases have been detected in Australia.

The Omicron variant has been the only “variant of concern” since Delta was downgraded by the WHO. (ABC News: Mark Leonardi)

Epidemiologist Jodie McVernon said Australia appeared to be moving away from “big surges and outbreaks” to “a more endemic state”, but warned that monitoring new sub-variants remained key.

“We need to monitor really closely whether a strain that is dominant in one place will have an advantage in another,” says Professor McVernon, who is director of epidemiology at the Doherty Institute.

“That’s the kind of thing researchers are on the lookout for … looking for variants of concern to see if they have distinct immune-escape properties.”

In China, the unprecedented surge in COVID-19 cases since the country abandoned its zero-COVID approach has fueled concerns that rampant, rapid transmission could give rise to a new variant of concern.

In general, the more a virus spreads, the more opportunities it has to evolve.

But Professor Holmes said the fact that the Chinese population was so susceptible to COVID-19 – due to a lack of previous immunity – meant the virus was under no pressure to mutate.

“In that kind of naive population, you won’t see a strong selection pressure because the virus doesn’t have to be selective, since there’s no immunity in the population to stop it,” he said.

“[The virus] wasn’t going to opt for a new variant… just the fastest kind.”

The next 12 months

Asked what might happen over the next 12 months, Dr Turville said he didn’t like to “crystallise” about what variants may or may not do. But if he were to make a guess, he said the virus is likely to follow one of three trajectories.

The first – and most optimistic – scenario would see the vast majority of Australians up to speed on their booster vaccines, including the newly available bivalent shots, which would help “suppress the virus”.

“Often, what [the virus] does to circumvent the antibody response is that it might have to drop something that gives it a fitness gain,” he said.

In other words, the virus may have to make some kind of biological trade-off because it can’t always do everything well at once.

“We might have a situation where we can slowly but surely change the virus to be less fit … and in that context we’ll hopefully see the reproduction rate go down, so [the virus] cause smaller waves, and put less pressure on hospitals.”

The second scenario, which he believes is most likely, looks not unlike our current COVID-19 situation: lagging stimulus rates and “not much political discussion” mean we face an “era of complacency,” he said. he said.

“When a new [variant] enters the community, it is not under as much pressure and it has the ability to spread … and it can make waves bigger than we would expect.

“Unfortunately, this will create situations where people who are vulnerable can become infected and this can lead to complications.”

In the third, “worst case” scenario, the virus could evolve into something we cannot predict.

“We can find that the virus is seismically shifting … a variant appears that is incredibly immune-evasive and can ride a very large wave,” Dr Turville said.

“We could also have a situation where we could see increased disease severity … But I would say from what we’re seeing in the variants we’re monitoring, the last scenario has the lowest probability.”

Professor Holmes agreed that the virus was unlikely to become more virulent, but said he would not rule anything out.

“What we saw with Omicron is a virus that is less able to infect the deep lungs because it has specialized more in the cells of the upper airways and this increases transmission.

“If it continues that process, you would expect it not to change back to a more virulent thing.”

Will COVID become seasonal?

While COVID-19 waves have been mostly “globally synchronized” to this point, Professor Holmes said that increased immunity means we may start to see more seasonal patterns emerge.

About 70 percent of the world’s population has now received at least one dose of a COVID-19 vaccine.

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“The more immunity you have in the population, the harder it is for the virus to spread, so optimal climatic conditions for its spread become more important.”

In Australia, Professor McVernon said she expected some ongoing transmission with “some seasonal outbreaks from time to time, a bit like flu”.

But Dr Turville said he was not yet convinced that COVID-19 could be considered a seasonal virus.

“There are many things we are still learning in real time about the virus and the effects of the virus infecting different populations,” he said.

“While we like to draw analogies to things like the flu and talk about it in predictable and seasonal terms, I don’t think we’re quite there yet.”

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