COVID-19: Is SARS-CoV-2 evolving differently after omicron

Cases are expected to rise with the advent of winter

By Taran Deol
Published: Wednesday 12 October 2022

More than 300 sub-variants of omicron are currently being tracked by the World Health Organization to gauge what new turn the pandemic may take. Cases are expected to rise with the advent of autumn and winter. But it remains uncertain which variant would be the driving force.

The age of omicron has already seen its lineages — BA.1, BA.2 and BA.4/BA.5 — cause distinct waves. But currently, five offsprings which have acquired growth advantages are collectively driving up cases in the world. The front-runners are BQ.1.1, BA.2.3.20, BQ.1, XBB and BA.2.75.2. Even among these, there are geographic heterogeneities.

The XBB recombinant is dominating in Asia, an analysis by Tom Wenseleers — an evolutionary biologist at the Catholic University of Leuven in Belgium — showed. 

This may soon become the case for Europe, where BQ.1.1 has secured the top place for now. It appears BQ.1.1 is also behind the COVID-19 cases in North America, Wenseleers’ analysis revealed. 

The nomenclature of the omicron sub-lineages is getting difficult to keep up with. But there are some similarities. They have begun accumulating the same mutations to evade immunity. 

 “Although these derivative sub-variants appear to diverge along the evolutionary course, the mutations they carry on the receptor-binding domain converge on the same sites,” an October preprint published in bioRxiv argued.

This phenomenon is called ‘convergent evolution’. The mutations that helped the virus evade certain antibodies are found repeatedly by the virus in various lineages. 

The sub-variants are divergent in terms of their ancestry but convergent in terms of the mutations, Anurag Agarwal, dean of the biosciences department at Ashoka University, explained.

“For SARS-CoV-2, we haven’t seen rapid within-clade evolution before,” Ryan Gregory, an evolutionary biologist and professor at the University of Guelp’s Biodiversity Institute of Ontario in Canada, told Down To Earth.

There are multiple immune-escaping variants, all increasing at the same time. And this is happening even during summer — flu is seasonal by contrast, he added.

Why it is different this time

How the SARS-CoV-2 virus is evolving now is unlike what we had seen up until last Thanksgiving when the fifth variant of concern was detected in South Africa.

“At the beginning of the pandemic, there was no pre-existing immunity so there was relatively limited pressure on the virus to change,” Marc Johnson, professor of molecular microbiology and immunology at the University of Missouri’s School of Medicine, told DTE.

The Wuhan strain will be the trunk if we try to illustrate a family tree of the SARS-CoV-2 virus. It slowly branched into the alpha variant on one side, followed by the emergence of new branches — beta, gamma, lambda and mu.

Delta emerged from an entirely different side of the tree, replacing everything we had seen up until now. Omicron did the same when it was spotted last November.

“They share a more distant common ancestor, but each one was not derived from the one that caused a wave before it,” Gregory explained. Now, it is the omicron canopy that continues to expand. 

While several changes occur in a virus’ genome, they cannot evolve indefinitely. Most genetic errors are neutral mutations and they do not help the virus. Many mutations are harmful to the virus and those are not seen in the variants circulating because they don’t survive.

Only a small fraction of mutations provide some growth advantage and those are the ones we predominantly see in the variants of concern.

“Convergent evolution occurs when species occupy similar ecological niches and adapt in similar ways in response to similar selective pressures,” Science Direct noted

The ecological niche describes how a species interacts within an ecosystem.

But after so much immunity, derived from both infection and vaccination, the space for selecting new variants is shrinking for the virus, virologist Shahid Jameel said. It’s possible SARS-CoV-2 has finally saturated its mutation space, he added.

Researchers have often used the convergent evolution phenomenon as a proxy to understand the “visible manifestation of the power of natural selection,” a 2019 study published in The Royal Society stated.

An often-cited example to better understand convergent evolution is the similarities between birds, bats and insects. All of them belong to different groups of animals but have had similar evolutionary paths that gave them wings to fly.

But what determines which lineage of omicron will dominate in which geographic region? This can be explained by what Jameel calls the ‘bottleneck effect’. “It’s simply a matter of introduction — only certain things go through the bottleneck,” he said.

The cloud of sub-variants we see now are by no means identical despite having similar sets of mutations, Gregory argued.

Some could have other properties that give them an advantage in certain host populations but not others. Luck could determine which ones take off and which don’t in different regions, he added in the same vein as Jameel.

While no new distinct variants are erupting, there are slight new changes here and there in the existing variants. This is essentially a function of broader pre-existing immunity. This immunity forces the virus to adapt rapidly, resulting in recurring mutations that allow it to be immune evasive. This virus behaviour can be termed ‘antigenic drift’ — a term traditionally used to describe small changes in the surface of the influenza virus.

Experts are still cautious about predicting where the pandemic is headed. Currently, some 1,700 people are still dying daily due to COVID-19, a seven-day-rolling average calculated by Our World in Data revealed.

The arrival of the omicron sub-lineages has worrying implications. Vaccines continue to protect against severe disease and death, aided by timely booster shots. But, monoclonal antibody therapies are slowly being rendered ineffective as the virus evolves. 

Most recently, the United States of America’s Food and Drug Administration issued a warning about Evushield on 3 October for failing to neutralise certain variants. It is the only pre-exposure prophylaxis treatment authorised under Emergency Use Authorisation.

Pre-exposure prophylaxis is the use of medications to prevent the spread of disease in people who have not yet been exposed to a virus.

But Johnson believes there is no reason to think the virus will become deadlier since there is no advantage for the virus to kill its host. 

Predicting pathogenicity is much more complex than predicting immune escape just by looking at the mutations, Gregory underlined.

“I mainly expect to see continued immune evading changes that adapt to changes in our immunity,” Johnson said.

We cannot rule out another divergent evolution in the SARS-CoV-2 virus genome. But even then, the end effect will remain the same. With a very high caseload, as is the case with COVID-19, even things that are less likely can come true, because it’s less likely per case. “Omicron itself was an unlikely emergence in terms of its multiple mutations”, Agarwal remarked. 

Older variants may persist in an immunocompromised individual even when they are no longer in circulation. They may undergo evolution within a single host.

It may be tempting to conclude that convergence means the virus will become stuck in a blind alley and won’t be able to evolve in another direction in the future, said Gregory.

“To this, I always refer back to Orgel’s Second Rule: Evolution is cleverer than you are,” Gregory said.

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