‘Concerning’ mutation detected in samples of UK coronavirus variant

Mutation known as E484K detected in 11 sequences of British variant, sparking fears virus is further evolving

Samuel Lovett@samueljlovett
Tuesday 02 February 2021 12:18
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Scientists are fearful that the coronavirus variant first found in Britain is further mutating to acquire the same concerning characteristics seen in the South African and Brazilian versions.

Analysis from Public Health England (PHE) has shown that the mutation known as E484K has been observed in 11 sequences of the British variant, named B.1.1.7.

This particular mutation changes the shape of the virus’ spike protein – which is responsible for gaining entry to human cells – in a way that makes it less recognisable to the body’s immune system and more resistant to the current generation of Covid vaccines.

E484K features in the genetic make-up of both the South African and Brazilian variants, and now genome sequencing has identified natural occurrences of this highly concerning mutation in B.1.1.7.

Read more: Follow live updates as ‘concerning’ mutation detected in samples of UK variant and door-to-door testing begins

“The mutation of most concern, which we call E484K, has also occurred spontaneously in the new Kent strain in parts of the country too,” professor Calum Semple, a member of the government’s Scientific Advisory Group for Emergencies, told BBC Radio 4’s Today programme. 

The 11 cases were detected among a dataset of 214,159 sequenced genomes, PHE said in a recent scientific briefing. PHE did not specify how prevalent the mutation was thought to be among UK cases, but said that “preliminary information suggests more than one acquisition event”.

Dr Julian Tang, a virologist at the University of Leicester, said this “is a worrying development, though not entirely unexpected”.

“The acquisition [of the E484K mutation] may be due to recombination with one of the South African/Brazilian variant viruses that may have co-infected the same cell - as we see with different influenza viruses - but this is rarer with coronaviruses,” he explained.

“If this E484K mutation is acquired by most of the UK B.1.1.7 variants - the recent reassurances from recent studies showing that the mRNA vaccines will still offer optimum protection against the original UK variant - may no longer apply.”

Professor Lawrence Young, a virologist at the University of Warwick, said the presence of E484K meant “the virus is very likely to be adapting to our immune response”.

Research has shown that the British variant in its current form, which is thought to be more transmissible and deadly than the original virus, can be neutralised by the Covid-19 vaccines.

Four of the five the leading vaccines have been shown to be effective in neutralising B.1.1.7, with Oxford University currently assessing how its own candidate is affected by the variant.

However, studies have shown that the South African variant, known as 501Y.V2, is capable of evading parts of the immune response induced by natural infection or vaccination.

Because of this, the effectiveness of the vaccines is thought to be diminished by 501Y.V2 – though it’s believed the jabs still remain capable of preventing severe disease, hospitalisation and death among those exposed to the virus.

Simon Clarke, an associate professor in cellular microbiology at the University of Reading, explained that “mutations arise spontaneously and thrive if they provide the virus with an advantage.”

“In lab studies, this [E484K] mutation meant that antibodies were less able to bind to the virus’ spike protein in order to stop it from unlocking human cells to gain entry,” he added.  

“Clinical trials by Novavax and Johnson & Johnson showed that their new vaccines were less effective in South Africa, compared to the UK or USA, and it is presumed that it was because of the high level of virus carrying this E484K mutation.”

It remains unclear whether the vaccines will be able to effectively neutralise the Brazilian variant, which shares many mutations with 501Y.V2.

Professor Sir Mark Walport, former chief scientific adviser to the government, said he was "more worried" about the Brazilian variant than the one that first emerged in South Africa.

"I'm concerned about the South African variant – it is more transmissible and the evidence is that the vaccine protects against it slightly less well – but the answer is that the current vaccine still work pretty well against this variant,” he told Times Radio.

"The South African variant is an example of others that are cropping up around the world and the one I think we should be more worried about is the variant that's emerged in South America."

Prof Semple said it was important to "snuff out" the South African variant, which has now been linked to 105 cases in the UK, and “allow the vaccine schedule to get ahead of it”.

Eleven of these infections were found to be community-based and not linked to people who had travelled to South Africa, suggesting the virus is now circulating among local populations.

They infections were detected in eight different English postcodes: in Hanwell, Tottenham and Mitcham in London; Walsall in the West Midlands; Broxbourne, Hertfordshire; Maidstone, Kent; Woking, Surrey; and Southport, Merseyside.

In response, an intensive “surge” programme of PCR testing is to be introduced to the different postcode areas – home to roughly 10,000 people each – where local residents are being urged to take a test.

Local health teams will be carrying out door-to-door screening while mobile testing units are to be introduced to each area in a bid to pick up any further cases linked to the South African variant.

"The huge effort to test and trace and observe for reinfections and readmissions is incredibly important to help us understand what is going on here, but the honest answer is that we really just don't know about the clinical importance of this,” Prof Semple said.

"But certainly we don't want a virus like this spreading throughout our community and taking advantage of the lack of immunity that we currently have."

Prof Semple said that while it is important to restrict the movement of people as much as possible, it is not practical to close the UK's borders completely.

"You can't do it altogether when you have got a country that is dependent on imports for food and other essential processes. It is just not possible," he said.

Andrew Hayward, professor of infectious disease epidemiology at University College London (UCL) and a member of Sage, said the 11 cases of the South African variant identified in the community are the "tip of the iceberg".

"This variant is identified through genetic sequencing and we sequence between 5 per cent and 10 per cent of all cases, so you can immediately tell from that that we have a big under-estimation of the number of cases,” he told Sky News.

He said the 11 infections could be multiplied "by quite a high level", adding: "We would expect we're seeing the tip of the iceberg of community transmission."

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