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Of all the variants so far, B.1.1.529 is causing the most alarm. And with good reason.
The “omicron” variant, as it is was named on Friday by the World Health Organisation, has an eye-watering number of mutations, many of which could help it dodge immunity, or make it more infectious.
Since delta, there have been eight other variants named after letters of the Greek alphabet by the organisation, but none have triggered this much worry.
The variant was first spotted in Botswana on Nov 11, and cases have now been found in South Africa, Israel and Hong Kong.
The most concerning changes have happened to the spike protein, where there are about twice as many mutations as the delta variant.
When Dr Tom Peacock, a virologist at Imperial College London, spotted the mutations 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.
‘Causing real concern’
One senior UK health official said that the spike protein on the omicron variant was “so dramatically different” that it was “causing real concern”, although there are currently no cases in Britain and it has not yet been classified as a variant of concern.
“It is the worst variant I have seen so far. We have protein experts and virologists who are all extremely concerned,” the official said.
The variant has about 50 mutations, with 30 in the spike protein and 10 in the receptor binding motif, the part that binds to our cell receptor called ACE2, which is greater than any other mutated strain.
Spike proteins are little grappling hooks on the surface of the virus which it uses to latch on to human cells.Video player from:
Changes to the spike protein are particularly concerning because vaccines have been designed to help the body recognise the spike shape. If they change too much, the immune system will be blind to an infection.
Put simply, vaccines would stop working and all our hard won protection would be lost.
Antibodies made by the body from a natural infection may also struggle to see off this new interloper.
There are also mutations at the furin cleavage site, which is alarming as this is an area that helps the virus get into human cells, and which makes it so infectious.
One mutation, P681H, has previously been found in alpha, mu and some gamma cases. But this is the first time that two changes have been seen in a single variant.
These changes 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.
As if this were not enough, there are also several changes that have never been seen before, which are also alarming scientists.
‘More of a hit on vaccines than anything we’ve seen so far’
Dr Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Centre in Seattle, said that many mutations, particularly E484, G446, K417 and Q493, were at “peak escape sites”, meaning that many antibodies would be impacted.
“This does not mean that the [omicron] variant will fully escape vaccine or infection-elicited antibodies. It takes many many mutations to fully escape neutralisation, and there are also T-cells,” he said.
“But 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 is also suggesting that omicron could cause serious problems.
In South Africa, the variant is currently spreading in Gauteng province. Positivity rates in Tshwane, part of Gauteng, have increased massively in the past three weeks, from less than one per cent to more than 30 per cent.
Sequence data showed that the majority of samples in the area are now omicron, with the variant having taken over from delta and C.1.2, another concerning variant which shares the same furin cleavage site mutation.
New variant ‘seems to spread very quickly’
Prof Tulio de Oliveira, the director of the Centre for Epidemic Response and Innovation in South Africa, said: “This new 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 slightly positive element 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 currently remains low, but senior health sources said there was a “high risk” of importations, which is expected to rise in the coming weeks as the virus spreads more widely.
Health officials are now watching reinfection data closely to see how many people are being infected from each case. That will give an indication of how much more transmissible it is.
Prof Sharon Peacock, the director of the Covid-19 Genomics UK Consortium, said: “This situation is reminiscent of the epidemiology of alpha in Kent around a year ago. There was a surge in cases, but it was not clear whether this was due to one or more super-spreader events or was associated with a more transmissible virus.
“The genetic difference of B.1.1.529 has led to the hypothesis that this may have evolved in someone who was infected but could then not clear the virus, giving the virus the chance to genetically evolve – the equivalent of an evolutionary gym.”
It will be several more weeks or months before we know if it is also more deadly.
Scientists have also started lab experiments to see how well antibodies neutralise the virus, which will also give an indication of how much more infectious it is.
For now, all the world can do is hold its breath and hope for the best.
