Researchers who track coronavirus mutations have spent the week poring over the details of a new variant detected this month in Botswana.
It is the latest in a ever-growing line of more than 1,500 recognised lineages of the Sars-Cov-2 virus to emerge since the pandemic began. In a sign of the anxiety over the threat from new variants, the UK and Israel on Thursday evening imposed travel restrictions on a group of southern African countries in response to the unusually high number of spike mutations in the new B.1.1.529 strain.
The question of whether a more transmissible, more deadly or even vaccine-resistant strain could replace the dominant Delta variant, which emerged in India late last year, is one that keeps scientists and health officials on high alert.
“Has Sars-Cov-2 tried all its tricks? You’d have to be pretty cavalier to believe that,” said Gavin Screaton, an immunologist and head of Oxford university’s medical sciences division.
The virus is changing all the time: every replication brings new errors on the string of 30,000 nucleotides that make up its genome.
Typically, these mutations fizzle out, but each one comes with the remote possibility of the virus becoming fitter, possibly enabling it to produce a higher viral load, bind more easily to cells in the airways or evade the body’s immune defences.
Before Delta, the biggest threat came from the fast-spreading Alpha variant in the UK. A dozen strains have been classified as variants of “concern” or “interest” by the World Health Organization and given official Greek alphabet names, the latest being the Mu variant that emerged in Colombia in January.
Last month, British authorities began monitoring a Delta subvariant which could be about 10 per cent more transmissible. Two more Delta descendants, found recently in Canada and Indonesia, share similarities with the strain.
“It’s been largely uneventful since Alpha and Delta popped up at the tail-end of last year,” said Emma Hodcroft, an evolutionary geneticist at the University of Basel who was one of the first to track mutations. “But the virus is always searching for its next move.”
There is no one reason why a more dangerous variant has not emerged, although experts agree that the global vaccination campaign has helped slow the mutations.
Before the vaccine rollout, the virus faced a “simpler immune landscape” in which almost everyone was susceptible and “transmissibility was the easiest win”, Hodcroft explained.
Now, with global first-dose coverage of more than 53 per cent and about 30m jabs being administered globally each day, the virus’ next move was “less cut and dried”. “It could become yet more transmissible or find ways of evading our immune response — or do both,” she said.
Some say transmissibility has already peaked. Francois Balloux, director of the University College London Genetics Institute, said the R0 — the reproduction number in a completely exposed population — of the endemic coronaviruses circulating before Sars-Cov-2 topped out at 7, following decades of natural selection.
As Delta has an R0 of between 6 and 7 — which is more than double that of the original Wuhan strain — the dominant variant may not have “much room to become more contagious in the short term”, he said.
Balloux predicted Sars-Cov-2 would fall into a pattern where it “slowly evolves a way around the immune system” over the course of a decade rather than “continual jumps in transmissibility”. The same, drawn-out evolution can be observed in influenza and seasonal coronaviruses.
But scientists remain concerned about a sudden virus mutation, throwing the global pandemic response and the vaccination drive off course.
The B.1.1.529 strain, which is spreading in South Africa as well as Botswana, has raised concerns for this reason, as many of its 32 mutations are associated with the ability to evade the immune system and spread faster.
The WHO has convened an emergency meeting on Friday, where it is expected to classify the strain as a variant of interest, according to one person with knowledge of the matter.
Tulio de Oliveira, director of the Centre for Epidemic Response and Innovation in South Africa, said he was “worried” about the variant and that it was the cause of about 90 per cent of the roughly 1,100 virus cases registered on Wednesday in Gauteng province. Unusually, he said, the strain could be detected by analysing results of regular PCR tests without using genomic sequencing.
“The key question to be answered is what exactly is the [variant’s] effect on the vaccines,” he added.
Slawomir Kubik, a genomics research expert at Geneva-based biotech Sophia Genetics, stressed that the “fitness” of a variant can only be judged by how it “spreads in the real world”.
“It’s about the genes, the environment and a degree of luck . . . If you have an ‘advantageous’ mutation but never pass it on, it will never spread,” he said.
Even if the Botswana strain fades, others will emerge. Venky Soundararajan, chief scientist at Nference, a data analytics company, worried that an effect of the inoculation drive could be to force the virus down “genetic cul-de-sacs”, spawning an “escape variant” capable of evading the immune system.
“Vaccines are a God-send in their ability to stop infections and severe disease, but paradoxically they also increase the need for us to monitor for these very specific, targeted mutations,” he said.
Soundararajan warned the unequal distribution of sequencing technology had created “gaping holes” in genomic surveillance. More than 80 per cent of the 5.4m Sars-Cov-2 genomes uploaded to the Gisaid global repository have come from just two continents: North America and Europe.
While no one can be sure where and when a dominant variant will emerge, there is scientific consensus that Delta will not remain in the ascendancy forever.
Kevin McCarthy, professor of microbiology and microgenetics at the University of Pittsburgh, said the virus’ evolution was “nearing a tipping point” after which the odds would favour an escape variant.
“Will we move to something where the virus alters its antigenicity and erodes vaccine efficacy? I think that’s likely to happen,” he said. “If the virus is faced with the binary choice of evolving or going extinct, it will evolve.”
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