Variant’s ‘horrific’ set of mutations put scientists on alert
Of all the variants so far, B.1.1.529 is causing the most alarm. And with good reason. The omicron variant has an eyewatering number of mutatations, many of which could help it dodge immunity or make it more infectious.
Since delta there have been eight variants named sequentially after letters of the Greek alphabet by the World Health Organisation (WHO), but none has triggered as much fear.
The omicron variant was first spotted in Botswana on November 11 and it has now been found in South
Africa, Israel, Hong Kong and Belgium. It is unlikely we will keep it out of Britain. It may already be here.
The most concerning changes have happened in its spike protein, which houses about twice as many mutations as the delta variant.
When virologist Dr Tom Peacock, of Imperial College, spotted the mutatations in the sequence data earlier this week he labelled them “horrific” and “really awful”.
“I would take a guess that this would be worse antigenically than nearly anything else about,” he said.
One senior UK health official said the spike protein on the omicron variant was “so dramatically different” that it was “causing real concern”, although there no cases of it in Britain and it is not yet a “variant of concern”.
Dr Susan Hopkins, the chief medical adviser at the UK Health Security
Agency, said: “It’s the most worrying variant we’ve seen.
“It has mutations that increase infectivity, mutations that evade the immune response, both from vaccines and natural immunity, mutations that cause increased transmissibility and new ones we haven’t seen before.”
The variant has about 50 mutations, 30 in the spike protein and 10 in the receptor binding motif, the part that binds to a cell receptor, called ACE2, more than any other mutated strain.
Spike proteins are little grappling hooks on the surface of the virus that it uses to latch on to human cells.
Changes to the spike protein are particularly concerning because vaccines have been designed to help the body recognise the spike’s shape. If it changes too much, the immune system will be blind to an infection.
Prof Wendy Barclay, head of the
Department of Infectious Disease and chairman in influenza virology at Imperial College London, said: “The way that our responses work is that we make antibodies to several different places on the spike protein, those are called antigenic sites.
“A lot of variants have changes in particular places, which would throw off one set of antibodies, but your other antibodies would still see the spike protein.
“This variant has so many differences that nearly all of the antigenic sites we know about are changed on this virus. That would suggest that the ability of antibodies that are induced by the vaccines will be compromised in their ability to neutralise the virus.”
Antibodies made by the body after a natural infection may also struggle to see off this new interloper and there are also mutatations at the furin cleavage site, which is also alarming, as this is an area that also helps the virus get into human cells, and what makes it so infectious.
One mutation – P681H – has previously been found in alpha, omicron, and some gamma, but it is the first time that two changes have been seen in a single variant. These are likely to enhance the virus’s ability to enter cells, increasing viral load and making it more transmissible.
There are also two mutations in an area called the nucleocapsid – R203K and G204R – which were present in the alpha, gamma and lambda variants, and are known to increase infectivity.
Several changes identifed have never been seen before, and they are also alarming scientists.
Jesse Bloom, a virologist at Fred Hutchinson Cancer Research Center in Seattle, said that many mutations – particularly E484, G446, K417 and Q493 – were at “peak escape sites” and would affect many antibodies.
“I’d expect the omicron variant to cause more of a hit on vaccines and infection-elicited antibody neutralisation than anything we’ve seen so far.”
Aside from the theoretical science of why it could be more infectious and dangerous, real world data are also suggesting omicron is starting to cause serious problems. In South Africa, the variant is spreading in Gauteng province where positivity rates have increased from one to seven per cent.
Sequence data shows that the majority of samples in the area are now omicron, and that it has taken over from delta and C.1.2, another concerning variant that shares the same furin cleavage site mutation. It is out-competing other variants far faster than beta and even delta did.
Tulio de Oliveira, director of the Centre for Epidemic Response and Innovation, in South Africa, said: “This variant, B.1.1.529 seems to spread very quickly. In less than two weeks (it) now dominates all infections following a devastating delta wave in South Africa.
“We estimate that 90 per cent of the cases in Gauteng – at least 1,000 a day are this variant.”
The only slight positive is that a certain deletion on the spike protein means that it can be easily picked up through PCR testing, making it easier for the world to track.
The threat level remains low in Britain but senior health sources said there was a ‘high risk’ of importation, which was expected to rise in the coming weeks as the virus spreads more widely.
Prof Sharon Peacock, director of the Covid-19 Genomics UK Consortium, which is monitoring variants for the Government, said it would probably soon spread to Britain.
“There are two approaches to what happens next: wait for more scientific evidence – or act now and row back later if it wasn’t required.
“I believe that it is better to ‘go hard, go early and go fast’ and apologise if mistaken.
“There are sufficient red flags to assume the worst rather than hope for the best.”
‘I believe we should go hard … and go fast. There are sufficient red flags to assume the worst rather than hope for the best’