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World yet to see ‘full extent of coronavirus evolutions’, warns leading UK scientist

Exclusive: Genetics chief warns of more mutations but puts faith in vaccine

Samuel Lovett@samueljlovett
Monday 01 March 2021 22:32
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The world has yet to see “the full extent of the evolution” of coronavirus as it continues to adapt to humans, the head of the UK’s genetic surveillance programme has said.

Professor Sharon Peacock told The Independent that the dominance of the new and emerging variants, including the UK, South African and Brazilian versions, suggests the virus is approaching “a fitness peak”.

Across the globe, the same mutations have been cropping up independently in the spike protein of Sars-Cov-2 – a result of what is known as “convergent evolution”.

Faced with selective pressure from growing immunity levels, along with social-distancing measures that have sought to limit its spread, the virus has acquired certain characteristics that have allowed it to continue circulating.

“Lots of mutations have just lit up almost at the same time, which is really fascinating,” said Prof Peacock, who is director of the Covid-19 Genomics UK consortium (Cog-UK). “The one in Brazil, the first dated sample was 4 December, but I expect it probably predates that a bit. 

“It seems to me that around November there’s been a very high number of cases combined with a partially resistant population, which has led to this natural selection and convergent evolution.”

The Brazilian variant, known as P1, has been reported in 25 countries across the world, including the UK, where a total of six infections have been detected so far by Cog-UK.

However, officials are racing to hunt down one person whose identity and whereabouts is unknown. Public Health England believes the individual, who tested positive for P1, used a home kit on 12 or 13 February, but did not complete their registration form properly.

A number of other variants, including the one first identified in South Africa, have been picked up in Britain, raising questions over the country’s current border-control system, which was only implemented last month.

Having initially jumped from animals into humans, the virus appears to be still adapting to its new hosts and evolving towards an optimal state of efficiency that facilitates continued transmissibility and immune evasion, Prof Peacock added.

“We’re debating that a lot at the moment,” she said. “We’re trying to figure out what’s the ideal constellation of mutations that endows maximum fitness.”

The “infamous” E484K mutation that has emerged in the Sars-Cov-2 spike protein – and is found in the South African and Brazilian variants – is thought to help the virus partially evade neutralising antibodies produced by the body following natural infection or vaccination. 

Although the effectiveness of vaccines is likely to be diminished by those variants carrying E484K, limited evidence suggests the jabs still provide protection against severe disease, hospitalisation and death.

N501Y is another spike protein mutation of concern. It features in the UK, South African and Brazilian variants, and is associated with higher levels of transmissibility but does not appear to impact vaccine efficacy.

Prof Peacock said these mutations were a “signature of convergent evolution – they’re coming up all around the place and behave the same way”. However, she insisted scientists needed to keep an eye on the bigger picture.

“It’s likely that the virus will also be constrained by certain configurations of mutations, after which it could lose fitness and it would not be able to outcompete others.

“And there’s quite a lot of mutations we don’t really understand yet but are probably quite important that we’re really not talking about that much.

“There's also probably lots more out there at the moment but we’re not sequencing [enough to detect them].

“I don’t think we’ve seen the full extent of the evolution of the virus and what it can possibly do. The last few months, it’s like the time before variants and then the time of variants. Our whole mindset has been changed by that.”

She added that it was impossible to predict what sort of mutations would emerge and when.

Professor Eleanor Riley, an immunologist at the University of Edinburgh, explained that Sars-Cov-2 is evolving to become a “better human virus” but was “walking a bit of a tightrope”.

“Any mutation has to help it avoid existing antibodies but also retain that ability to fit our cells,” she told The Independent.

“So there will be some kind of constraints on how much that spike protein can vary to avoid our immune system while still being a very good fit for our cells. I think we don’t have an idea yet how much tolerance there is in that trade-off.

“I think over the next few months, we’ll start to see how much the virus can still vary.”

Prof Peacock said P1 is probably aligned with the South African variant in terms of the threat it poses. “It’s got the same mutations and the track record of transmissibility and interfering with immunity,” she said, pointing to the example of Manaus in Brazil where P1 has driven a large second wave in cases, despite previously high levels of immunity in the local population.

However, she warned that there was a “sparsity of data” surrounding P1 and it was too early to draw any firm conclusions. “We still don’t know much about it,” she said.

Despite the emergent variants, Prof Peacock insisted she remained “optimistic” about the trajectory of the pandemic given the success of the Covid-19 vaccines.

“I’m very positive about vaccination,” she said. “It might not completely eliminate reinfection, but because it reduces infection and reduces transmission, then we’re getting into a better ballpark. It’s not going to switch it [Covid-19] off, which is why we’ll never get rid of it, but I think it’s very positive.

“Is it possible that a variant could emerge which is a really tough nut to crack? It could, but we’ve got sequencing and we’ve got very good vaccine strategies. My sense is that we can keep ahead of it.

“We’ve developed all these vaccines so fast, so the idea that something would be completely untreatable and we’d have to go back to living in our bubbles, I’m hopeful that won’t happen. We just have to keep our eyes on the virus.”

Cog-UK is a network of public health bodies and laboratories based in the UK, and currently analyses more than 30,000 positive tests a week to survey and trace the evolution of the virus.

Roughly 5-10 per cent of positive tests in Britain are selected randomly to be sent on for further genome analysis, but Prof Peacock said this figure will rise as cases continue to fall across the population.

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