By Andrew Joseph Nov. 26, 2021
Scientists in South Africa have identified a new coronavirus variant with a worrisome combination of mutations that experts fear could make it more transmissible and allow it to evade immune protection — including the protection generated by vaccines.
Experts are scrambling to learn more about the variant, known by its scientific name B.1.1.529 and called Omicron by the World Health Organization. Right now, there are more open questions than firm answers. And although scientists have expressed significant early concern over the variant — the WHO designated it as a “variant of concern” on Friday — they have cautioned that they are still seeking critical information about it.
Below, STAT outlines what is known and unknown.
Related: Covid-19 vaccines flirted with perfection at first. Reality is more complicated
One reminder: There have been a series of variants that have caused initial alarm, only to prove largely unimportant in the course of the pandemic.
Where has it been detected?
Scientists in South Africa detected the lineage on Monday, according to the country’s National Institute for Communicable Diseases, and rang the alarm bell for the world. Researchers in Botswana and Hong Kong also posted sequences publicly, and other cases have since been reported in Belgium and Israel. The variant is likely in other countries, but researchers just haven’t picked it up yet.
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It’s not clear where the variant actually emerged. It could be that South Africa and Botswana saw it early because they have strong genetic sequencing networks.
On Friday afternoon, the United States joined other countries in imposing travel restrictions from those two countries, as well as Zimbabwe, Namibia, Lesotho, Eswatini, Mozambique, and Malawi, effective Monday.
Why is it causing concern?
Several reasons.
For one, it appears to be outcompeting other variants in South Africa — including the extremely transmissible Delta variant — and fast. It’s starting to drive cases up in that country, which has already had several massive waves in its epidemic. Some possible explanations are that it’s a better spreader than even Delta, that it can cause infections in people who are protected at higher rates, or some combination of the two.
But beyond the epidemiological landscape in South Africa, scientists are concerned because of the number and variety of mutations B.1.1.529 acquired — what Sharon Peacock, the director of the Covid-19 Genomics UK Consortium, called a “very unusual constellation of mutations.” Some mutations have been previously seen in other variants and are associated with increased transmissibility and the ability to get around immune protection.
Scientists can’t predict how different mutations will behave when combined, but of particular worry to scientists is that the virus has some 32 mutations in its spike protein, which is what vaccines teach our immune system to recognize and target.
The variant “has a very high number of mutations with a concern for predictive immune evasion and transmissibility,” said Tulio de Oliveira, director of the Centre for Epidemic Response and Innovation, who helped identify the variant in South Africa.
What does it mean for immune protection?
If the spike protein changes, the antibodies elicited by vaccines or an earlier infection can’t recognize it as well. The more changes, the more foreign that spike starts to look to the immune system.
Vaccines generate what’s called a polyclonal response, with lots of antibodies that recognize different pieces of the spike protein. Other variants have had mutations that caused changes in a particular spot on the protein — called an antigenic site — and might have thrown off those corresponding antibodies, but there were plenty of other antibodies that still could recognize the virus.
But with the new variant, “it has so many changes across spike that nearly all the antigenic sites we know about are changed on this virus,” said Wendy Barclay, who leads a U.K. group studying new variants of the SARS-CoV-2 coronavirus. That suggests, Barclay said, that the ability of antibodies “will be compromised in their ability to neutralize the virus” — though she cautioned that scientists need to study that question to confirm it.
So far, researchers don’t know exactly what size dent the variant might have on vaccine effectiveness; the question of immune escape is one of degrees, not all or nothing. Some variants that have emerged so far have had more of an impact on vaccine effectiveness than others, though the vaccines so far have been able to keep up with the variants. Scientists have also found that it would take lots of escape mutations in the right spots to enable the virus to fully evade immunity.
When a variant emerges, one of the primary questions is how well antibodies can still fight off the new form of the virus. But vaccines generate different layers of immune protection, including T cells. Scientists aren’t sure yet what the impact of the variant might be on those, though T cells seem to have been less affected by mutations in other variants (T cell responses to new viruses are more complicated to study than antibody responses). However, studies have shown that neutralizing antibody levels can act as a correlate for how well protected someone is.
One bit of good news: studies have suggested booster doses can, at least for a time, elicit such sky-high levels of antibody that they can broadly withstand a mutated virus, even if the antibodies aren’t targeting the specific viral proteins as well.
“Sometimes quantity can sort of compensate for the lack of match,” Barclay said.
Ali Ellebedy, an immunologist at Washington University School of Medicine in St. Louis, said he finds the new variant very concerning, but thinks it will be much more of a threat, if it takes off, to people who are unimmunized or who didn’t mount a strong response from the vaccine.
“It’s not the same ground anymore,” he said of the landscape of people susceptible to the virus. “It’s not as dry. If you think of it as a fire, yes, there are some dry patches there but there are some areas that have been damp and humid. And the fire is not going to find it easy. And that kind of makes sense because of that preexisting immunity.”
He said manufacturers should be testing updated vaccines that protect against Omicron, to be ready if it takes off.
Beyond vaccines, the variant could have a greater impact on the effectiveness of the monoclonal antibodies used as therapeutics.
How did it get so many mutations?
The virus picked up so many mutations so quickly that scientists speculate the variant might not have come from the average case of Covid. Most people clear the virus after an acute infection, but sometimes people with compromised immune systems develop chronic Covid infections. The virus essentially lives in these people for an extended period of time, and can rapidly accumulate mutations at a pace that viral evolution that occurs during normal transmission doesn’t produce. Scientists have hypothesized something similar led to the emergence of the Alpha variant last year.
Notably, the new variant is not a descendant of Delta. Delta has become so dominant globally that scientists had raised the idea that any future variant of concern would likely be a spinout of that virus.
How do scientists figure out what happens next?
Scientists around the world have already launched investigations into the variant.
For one, researchers will keep watching the situation epidemiologically. The variant took off in South Africa when cases there were quite low, so there’s a chance that its apparent growth is a result of a few superspreading events, for example, or tied to which cases are getting sequenced. But if it takes off in other countries, that will add to the evidence of its greater ability to spread.
Scientists will study the virus in lab experiments to see how well antibodies generated by vaccines or past infections can still recognize and neutralize the variant. Vaccine makers have already said they’re looking at the virus as well in case they need to update their shots.
Researchers will also be looking at whether cases tied to this variant are more or less likely to cause severe disease.
What does it mean for the rest of the world?
It’s too early to say. Some variants have taken off globally — take Delta — but other variants that caused concerns, such as Beta and Gamma, never really established toeholds beyond the regions where they first emerged. Variants can behave differently in different places, depending on what other versions of the virus are circulating and also on the levels of protection in a given place.
Why did the variant emerge?
There’s no real reason why a variant appears. It’s just the result of viral evolution.
But the emergence of the variant — if it did start in an African country, which remains unknown — could underscore the message from health advocates that the massive inequities in vaccine access are a global problem. The higher the levels of transmission that are allowed to persist, the greater the chance of new worrisome variants. Only about one in four people in South Africa is fully immunized.
Helen Branswell contributed reporting.
Andrew covers a range of topics, from addiction to public health to genetics.andrew.joseph@statnews.com@DrewQJoseph
What’s known and unknown about Omicron, the coronavirus variant identified in South Africa
