On 8 December, during a regular Tuesday meeting about the spread of the pandemic coronavirus in the United Kingdom, scientists and public health experts saw a diagram that made them sit up straight. Kent, in southeastern England, was experiencing a surge in cases, and a phylogenetic tree showing viral sequences from the county looked very strange, says Nick Loman, a microbial genomicist at the University of Birmingham. Not only were half the cases caused by one specific variant of SARS-CoV-2, but that variant was sitting on a branch of the tree that literally stuck out from the rest of the data. “I’ve not seen a part of the tree that looks like this before,” Loman says.
Less than 2 weeks later, that variant is causing mayhem in the United Kingdom and elsewhere in Europe. Yesterday, U.K. Prime Minister Boris Johnson announced stricter lockdown measures, saying the strain, which goes by the name B.1.1.7, appears to be better at spreading between people. The news led many Londoners to leave the city today, before the new rules take effect, causing overcrowded railway stations. The Netherlands, Belgium, and Italy announced they were temporarily halting passenger flights from the United Kingdom. The Eurostar train between Brussels and London will stop running tonight at midnight, for at least 24 hours.
Scientists, meanwhile, are hard at work trying to figure out whether B.1.1.7 is really more adept at human-to-human transmission—not everyone is convinced yet—and if so, why. They’re also wondering how it evolved so fast. B.1.1.7 has acquired 17 mutations all at once, a feat never seen before. “There’s now a frantic push to try and characterize some of these mutations in the lab,” says Andrew Rambaut, a molecular evolutionary biologist at the University of Edinburgh.
Too many unknowns
Researchers have watched SARS-CoV-2 evolve in real time more closely than any other virus in history. So far, it has accumulated mutations at a rate of about one to two changes per month. That means many of the genomes sequenced today differ at about 20 points from the earliest genomes sequenced in China in January, but many variants with fewer changes are also circulating. “Because we have very dense surveillance of genomes, you can almost see every step,” Loman says.
But scientists have never seen the virus acquire more than a dozen mutations seemingly at once. They think it happened during a long infection of a single patient that allowed SARS-CoV-2 to go through an extended period of fast evolution, with multiple variants competing for advantage.
One reason to be concerned, Rambaut says, is that among the 17 mutations are eight in the gene that encodes the spike protein on the viral surface, two of which are particularly worrisome. One, called N501Y, has previously been shown to increase how tightly the protein binds to the angiotensin-converting enzyme 2 receptor, its entry point into human cells. The other, named 69-70del, leads to the loss of two amino acids in the spike protein and has been found in viruses that eluded the immune response in some immunocompromised patients.
A fortunate coincidence helped show that B.1.1.7 (also called VUI-202012/01, for the first “variant under investigation” in December 2020), appears to be spreading faster than other variants in the United Kingdom. One of the polymerase chain reaction (PCR) tests used widely in the country, called TaqPath, normally detects pieces of three genes. But viruses with 69-70del lead to a negative signal for the gene encoding the spike gene; instead only two genes show up. That means PCR tests, which the United Kingdom conducts by the hundreds of thousands daily and which are far quicker and cheaper than sequencing the entire virus, can help keep track of B.1.1.7.
In a press conference on Saturday, Chief Science Adviser Patrick Vallance said B.1.1.7, which first appeared in a virus isolated on 20 September, accounted for about 26% of cases in mid-November. “By the week commencing the ninth of December, these figures were much higher,” he said. “So, in London, over 60% of all the cases were the new variant.” Johnson added that the slew of mutations may have increased the virus’ transmissibility by 70%.
Christian Drosten, a virologist at Charité University Hospital in Berlin, says that was premature. “There are too many unknowns to say something like that,” he says. For one thing, the rapid spread of B.1.1.7 might be down to chance. Scientists previously worried that a variant that spread rapidly from Spain to the rest of Europe—confusingly called B.1.177—might be more transmissible, but today they think it is not; it just happened to be carried all over Europe by travelers who spent their holidays in Spain. Something similar might be happening with B.1.1.7, says Angela Rasmussen, a virologist at Georgetown University. Drosten notes that the new mutant also carries a deletion in another viral gene, ORF8, that previous studies suggest might reduce the virus’ ability to spread.
But further reason for concern comes from South Africa, where scientists have sequenced genomes in three provinces where cases are soaring: Eastern Cape, Western Cape, and KwaZulu Natal. They identified a lineage separate from the U.K. variant that also has a N501Y mutation in the spike gene. “We found that this lineage seems to be spreading much faster,” says Tulio de Oliveira, a virologist at the University of KwaZulu-Natal whose work first alerted U.K. scientists to the importance of N501Y. (A preprint of their results on the strain, which they are calling 501Y.V2, will be released on Monday, de Oliveira says.)
Another worry is B.1.1.7 could cause more severe disease. There is anecdotal evidence that the South African variant may be doing that in young people and those who are otherwise healthy, says John Nkengasong, director of the Africa Centres for Disease Control and Prevention. “It’s concerning, but we really need more data to be sure.” The African Task Force for Coronavirus will convene an emergency meeting to discuss the issue on Monday, Nkengasong says.
Still, B.1.177, the strain from Spain, offers a cautionary lesson, says virologist Emma Hodcroft of the University of Basel. U.K. scientists initially thought it had a 50% higher mortality rate, but that turned out to be “purely messy, biased data in the early days,” she says. “I think that is a very strong reminder that we always have to be really careful with early data.” In the case of N501Y, more young people may be getting sick because many more are getting infected; Oliveira says some recent postexam celebrations in South Africa have turned into superspreading events. Studies in cell culture and animal experiments will have to show how a virus with several or all of the mutations carried by the new variant compares with previous variants, Drosten says.
Getting definitive answers could take months. But Ravindra Gupta, a virologist at the University of Cambridge, has made a start. The 69-70del mutation appeared together with another mutation named D796H in the virus of a patient who was infected for several months and was given convalescent plasma to treat the disease. (The patient eventually died.) In the lab, Gupta’s group found that virus carrying the two mutations was less susceptible to convalescent plasma from several donors than the wild-type virus. That suggests it can evade antibodies targeting the wild-type virus, Gupta wrote in a preprint published this month. He also engineered a lentivirus to express mutated versions of the spike protein and found that the deletion alone made that virus twice as infectious. He is now conducting similar experiments with viruses that carry both the deletion and the N501Y mutation. The first results should appear just after Christmas, Gupta says.
Does it occur elsewhere?
The ban on flights from the United Kingdom that other countries are imposing “is pretty extreme,” Hodcroft says. But it does give countries time to think about putting any additional measures in place to deal with passengers from the United Kingdom, she says: “I would hope that most countries in Europe are thinking about this.”
But scientists say B.1.1.7 may already be much more widespread. Researchers in the Netherlands have found it in a sample from one patient taken in early December, Dutch health minister Hugo de Jonge wrote in a letter to Parliament today. They will try to find out how the patient became infected and whether there are related cases. Other countries may have the variant as well, says epidemiologist William Hanage of the Harvard T.H. Chan School of Public Health; the United Kingdom may have just picked it up first because it has the most sophisticated SARS-CoV-2 genomic monitoring in the world. Many countries have little or no sequencing.
The evolutionary process that led to B.1.1.7 may also occur elsewhere. With vaccines being rolled out, the selective pressure on the virus is going to change, meaning variants that help the virus thrive could be selected for, says Kristian Andersen, an infectious disease researcher at Scripps Research. The important thing in the coming months will be picking up such events, Andersen says. “Whatever enabled the B.1.1.7 lineage to emerge is likely going on in other parts of the world,” he says. “Will we be able to actually detect it and then follow up on it? That, to me is one of the critical things.”
https://www.sciencemag.org/news/2020/12/mutant-coronavirus-united-kingdom-sets-alarms-its-importance-remains-unclear
