ScienceCOVID-19’s reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
Trucks on 21 December 2020 in the south-east of England on their way to France, after the border was closed, in an attempt to stop the distribution of a new SARS-CoV-2 variant.
PHOTO: DAN KITWOOD / GETTY BEELDE
On December 8, 2020, a small group of scientists in the UK signed up for a regular Tuesday video conference on the spread of the pandemic coronavirus. The discussion focused on Kent, a province in the southeast of England that has seen increasing distribution of SARS-CoV-2, even though the rest of the country has managed to limit the distribution. Because investigations found no obvious causes – no major outbreaks in the workplace or changes in people’s behavior – several researchers were asked to look at viral genomes from the region.
The genetic pedigree they presented showed something unusual was going on, says one of the participants, microbial genomic Nick Loman from the University of Birmingham. Not only were half of the cases in Kent caused by a specific variant of SARS-CoV-2, but its branch literally stands out from the rest of the data. “I’ve never seen a part of the tree that looks like that,” says Loman. And when scientists compared how quickly this variant, called B.1.1.7, and others spread, they made a surprising discovery: it seems that the virus has become more skilled at transmitting it between humans.
The discovery of the viral lineage, as well as a kind of concern in South Africa, had a great impact. On 19 December, British Prime Minister Boris Johnson announced that London and South East England would be placed under stricter COVID-19 restrictions to include the variant, which Johnson said was 70% more transferable. Although there is still no evidence that the tension is more deadly, many countries have closed their borders to travelers from the UK, pondering the possible new threat. Several announced that they also have the variation among their population.
Like this issue of Science went to press on December 23, scientists were still struggling to understand whether the variant really spreads faster, and if so, how. But its emergence has driven home the idea that viral evolution, which has so far had little effect on the trajectory of the COVID-19 pandemic, could still lead to nasty surprises – just as the first effective vaccines are being rolled out. It also raises the question of whether those vaccines need to be periodically updated to expire a changing virus.
The British generation of SARS-CoV-2 apparently contracted 17 mutations that lead to amino acid changes in its proteins at the same time, a performance never seen before in the coronavirus. Of paramount importance was that eight of them were in the gene encoding nails, a protein on the viral surface that the pathogen uses to enter human cells. “There is now intense pressure to try to characterize some of these mutations in the laboratory,” said Andrew Rambaut, a molecular evolutionary biologist at the University of Edinburgh.
Three already stand out as worrying. It was previously shown that a mutation called N501Y increases how tightly the peak binds to the angiotensin-converting enzyme 2 receptor, the main access point to human cells. Scientists in South Africa were the first to notice the importance of the N501Y: they noticed it a few weeks ago in a generation that was rising sharply in the provinces of the Eastern Cape, Western Cape and KwaZulu-Natal. “We have found that this genus appears to spread much faster,” said Tulio de Oliveira, a virologist at the University of KwaZulu-Natal whose work has warned British scientists about the mutation. This is worrying, says evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center: virus is. “
B.1.1.7’s second notable mutation, a deletion named 69-70del, results in the loss of two amino acids in the vein protein. It has also appeared before: it was found along with another mutation called D796H in the virus of a COVID-19 patient in Cambridge, UK, which was given as treatment to recovered patients but eventually died. In laboratory studies, the patient’s strain was less susceptible to recovery from multiple donors than wild-type virus, says Ravindra Gupta, a virologist at the University of Cambridge, who published the findings in a pre-print in early December.
Gupta also designed a lentivirus to express mutated versions of SARS-CoV-2’s peak and found that the virus alone makes the virus twice as contagious to human cells. A third mutation, P681H, is also something to look at, says virologist Christian Drosten of the Charité University Hospital in Berlin, because it changes the place where the ear protein is cut before it enters human cells.
The N501Y mutation affects amino acids (yellow) in the vein protein, which bind to a human receptor (green).
CREDITS: (IMAGE) SHUTTER SWITCHED BY GISAID; (DATA) EMMA HODCROFT / UNIVERSITY OF CHILDREN
New virus strains are common in outbreaks and often cause alarm, but few are ultimately consequent. British scientists and others were therefore initially wary of concluding that B.1.1.7’s mutations allowed the virus to spread better from person to person. But the new variant is rapidly replacing other viruses, says Müge Çevik, a specialist in infectious diseases at the University of St. Petersburg. Andrews. Exactly what impact each mutation has is much more difficult to assess than to detect it or show that it is on the rise, says Seema Lakdawala, a biologist at the University of Pittsburgh.
Animal experiments can help to show an effect, but they have limitations. Hamsters already transmit SARS-CoV-2 virus rapidly, for example, which can obscure any effect of the new variant. Ferrets transmit it less efficiently, so a difference can be more easily observed, says Lakdawala. ‘But can it really be translated to people? I doubt it. “A definitive answer could be months free, she predicts.
The number of mutations has also expressed concern that South African or British descent could lead to serious diseases or even cause immunity caused by vaccine. So far, there is little reason to think so. While some mutations prove to evade monoclonal antibodies, vaccines and natural infections appear to lead to a broad immune response targeting many parts of the virus, says Shane Crotty of the La Jolla Institute of Immunology. “It will be a big challenge for a virus to escape.” Measles and polioviruses have never learned to escape the vaccines targeted, and he notes: “These are historical examples that suggest we should not be afraid.”
At a press conference on 22 December, Uğur Şahin, CEO of BioNTech, pointed out that the British variant differs in just nine of more than 1270 amino acids from the peak protein encoded by the messenger RNA in the highly effective COVID-19 vaccine that developed his business with Pfizer. “It is scientifically probable that the immune response through the vaccine can also handle the new virus,” he said. Experiments are underway that should confirm this soon, Şahin added.
Another big question is how the virus accumulated a number of mutations at one time. So far, SARS-CoV-2 has usually contracted only one to two mutations per month. Scientists believe that the new variant could undergo a long evolution of a rapid evolution in a patient with chronic infection who transmitted the virus. “We know it’s rare, but it can happen,” said Maria Van Kerkhove, an epidemiologist at the World Health Organization.
Sébastien Calvignac-Spencer, an evolutionary virologist at the Robert Koch Institute, says the UK’s new COVID-19 closure and the closure of other countries’ borders is the first time that such drastic action based on genomic surveillance has combined with epidemiological data. “It’s quite unprecedented on this scale,” he says. But the question of how to respond to disturbing mutations in pathogens will be more prevalent, he predicts. Most people are happy that they have prepared for a Category 4 hurricane, even if the predictions turn out to be wrong, says Calvignac-Spencer. “It’s a bit the same, except that we have a lot less experience with genomic monitoring than with the weather forecast.”
For Van Kerkhove, the advent of B.1.1.7 shows how important it is to follow viral evolution closely. The UK has one of the most comprehensive monitoring systems in the world, she says. “My concern is: how much of this is happening worldwide, where we do not have the order of capacity?” Other countries need to step up their efforts, she says. And all countries must do what they can to keep the spread of SARS-CoV-2 to a minimum in the coming months, Van Kerkhove adds. “The more this virus circulates, the more likely it is to change,” she says. “We’re playing a very dangerous game here.”