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People at Saint Pancras station in London, waiting to board the last train to Paris today amid concerns that the borders with France will be closed. Belgium said today that it would ban trains from London for at least 24 hours.
Stefan Rousseau / PA via AP Images
By Kai Kupferschmidt
SciencesCOVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation.
On December 8, during a regular Tuesday meeting on the spread of the pandemic coronavirus in the UK, scientists and public health experts saw a diagram that made them sit up straight. Kent, in south-east England, was seeing an increase 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 of the cases caused by a specific variant of SARS-CoV-2, but that variant was sitting on a tree branch that literally stood out from the rest of the data. “I hadn’t seen a part of the tree that looked like this before,” says Loman.
Less than two weeks later, that variant is causing chaos in the UK and elsewhere in Europe. Yesterday, UK Prime Minister Boris Johnson announced tougher lockdown measures, saying that the tension, which goes by the name B.1.1.7, appears to be better at spreading between people. The news prompted many Londoners to leave the city today, before the new rules go into effect, leading to overcrowding of train stations. Also today, the Netherlands, Belgium and Italy announced that they would temporarily suspend passenger flights from the UK. The Eurostar train between Brussels and the British capital will stop running at midnight tonight for at least 24 hours.
Meanwhile, scientists are hard at work trying to find out if B.1.1.7 is really more adept at person-to-person transmission (not everyone is convinced yet), and if so, why. They also wonder how it evolved so fast. B.1.1.7 has acquired 17 mutations at once, a feat never seen before. “Now there is a frenzy to try and characterize some of these mutations in the laboratory,” says Andrew Rambaut, a molecular evolutionary biologist at the University of Edinburgh.
Too many unknowns
Researchers have observed the evolution of SARS-CoV-2 in real time more closely than any other virus in history. So far, you have accumulated mutations at a rate of about 1 to 2 changes per month. That means that many of the genomes sequenced today differ by around 20 points from the first genomes sequenced in China in January, but many variants with fewer changes are also circulating. “Because we have very dense surveillance of the genomes, you can almost see every step,” says Loman.
But scientists have never seen the virus acquire more than a dozen mutations apparently at once. They believe it happened during a prolonged single-patient infection that allowed SARS-CoV-2 to go through a prolonged period of rapid evolution, with multiple variants vying for the upper hand.
One reason to be concerned, Rambaut says, is that among the 17 there are two concerning mutations in the gene that codes for the spike protein on the viral surface. One, called N501Y, has previously been shown to increase the strength with which the protein binds to the ACE2 receptor, its point of entry into human cells. The other, called 69-70del, leads to the loss of two amino acids in the spike protein and has been found in viruses that elude the immune response in some immunosuppressed patients.
Now there is a frenzy to try to characterize some of these mutations in the laboratory.
A lucky 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 UK. One of the most widely used PCR tests in the country, called TaqPath, typically detects fragments of three genes. But viruses with 69-70del lead to a negative signal for the gene encoding the spike gene; instead, only two genes appear. That means PCR tests, which the UK runs in the hundreds of thousands daily and which are much faster and cheaper than sequencing the whole virus, can help track B.1.1.7.
At a news conference on Saturday, Chief Scientific Advisor Patrick Vallance said that B.1.1.7, which first appeared in an isolated virus on September 20, accounted for about 26% of cases in mid-November. “For the week that started Dec. 9, these numbers were much higher,” he said. “So in London, more than 60% of all cases were the new variant.” Boris Johnson added that the large number of mutations may have increased the transmissibility of the virus by 70%.
Christian Drosten, a virologist at the Charité University Hospital in Berlin, says it was premature. “There are too many unknowns to say something like that,” he says. On the one hand, the rapid spread of B.1.1.7 could be due to chance. Previously, scientists were concerned that a variant that spread rapidly from Spain to the rest of Europe – confusingly called B.1.1.77 – might be more transmissible, but today they believe it is not; it was simply taken all over Europe by travelers who were spending their holidays in Spain. Something similar could be happening with B.1.1.7, says Angela Rasmussen, a virologist at Georgetown University. Drosten points out that the new mutant also carries a deletion in another viral gene, ORF8, which previous studies suggest could reduce the virus’s ability to spread.
But another cause for concern comes from South Africa, where scientists have sequenced genomes in three provinces where cases are on the rise: Eastern Cape, Western Cape and KwaZulu Natal. They identified a separate lineage of the UK variant that also has the N501Y mutation in the spike gene. “We found that this lineage seems to spread much faster,” says Tulio De Oliveira, a virologist at the University of KwaZulu Natal, whose work first alerted UK scientists to the importance of N501Y. (A preprint of the results of the strain will be released on Monday, which they call 501Y.V2, says De Oliveira.)
Another concern is that B.1.1.7 could cause more serious illness. There is anecdotal evidence that the South African variant may be doing that in the young and those who are otherwise healthy, says John Nkengasong, director of the African Centers for Disease Control and Prevention. “It is concerning, but we really need more data to be sure.” The African Coronavirus Task Force will convene an emergency meeting to discuss the issue on Monday, Nkengasong says.
Still, B.1.1.77, the strain from Spain, offers a cautionary lesson, says virologist Emma Hodcroft of the University of Basel. UK scientists initially thought it had a 50% higher death rate, but it turned out to be “purely messy and skewed data in the early days,” she says. “I think it’s a very strong reminder that we always have to be very careful with early data.” In the case of N501Y, younger people can get sick because many more are getting infected; Oliveira says that some post-exam celebrations in South Africa have turned into wide-spread events. Studies in cell culture and animal experiments should show how a virus with several or all of the mutations carried by the new variant compares with previous variants, says Drosten.
Getting definitive answers could take months. But Ravindra Gupta, a virologist at the University of Cambridge, has started. The 69-70del mutation appeared together with another mutation called D796H in the virus of a patient who was infected for several months and received convalescent plasma to treat the disease. (The patient eventually died). In the laboratory, Gupta’s group found that the virus carrying the two mutations was less susceptible to convalescent plasma from multiple donors than the wild-type virus. That suggests it can evade antibodies directed against 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 removal alone made the virus twice as infectious. He is now conducting similar experiments with viruses that carry both the N501Y deletion and mutation. The first results should appear right after Christmas, says Gupta.
Does it occur elsewhere?
The ban on flights from the UK being imposed by other countries “is quite extreme,” says Hodcroft. But it gives countries time to think about implementing additional measures to deal with UK passengers, he says: “I hope most countries in Europe are thinking about this.”
But scientists say that B.1.1.7 may already be much more widespread. Dutch researchers found it in a sample from a 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 got infected and if there are any related cases. Other countries may have the variant as well, says epidemiologist William Hanage of the Harvard TH Chan School of Public Health; The UK may have caught it first because that country has the world’s most sophisticated SARS-CoV-2 genomic monitoring. Many countries have little or no sequence.
The evolutionary process that led to B.1.1.7 may also occur elsewhere. With the implementation of vaccines, the selective pressure on the virus will change, meaning that variants could be selected that help the virus thrive, says Kristian Andersen, an infectious disease researcher at Scripps Research. The important thing in the coming months will be to collect these types of events, says Andersen. “Everything that allowed the B.1.1.7 lineage to emerge is probably happening in other parts of the world,” he says. “Will we be able to detect it and then follow it up? That, for me, is one of the critical things.”
