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ScienceCOVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation.
Trucks en route to France line up in the south-east of England on December 21, 2020 after the border was closed to try to stop the spread of a new variant of SARS-CoV-2.
PHOTO: DAN KITWOOD / GETTY IMAGES
On December 8, 2020, a small group of scientists from the UK logged in for a regular video conference on Tuesday on the spread of the pandemic coronavirus. The discussion focused on Kent, a county in south-eastern England that was seeing increasing transmission of SARS-CoV-2, even as the rest of the country managed to curb its spread. Because the investigations had found no obvious causes – no large outbreaks in the workplace or changes in people’s behavior – several researchers were invited to examine the region’s viral genomes.
The genetic family tree they presented showed that something unusual was happening, says one of the participants, microbial genomicist Nick Loman of 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 stood out from the rest of the data. “I’ve never seen a part of the tree that looks like this before,” Loman says. And when scientists compared the speed of spread of this variant, named B.1.1.7, and others, they made a startling discovery: the virus seemed to have become more able to pass between people.
The discovery of the viral lineage, as well as an equally disturbing lineage in South Africa, had a huge impact. On December 19, British Prime Minister Boris Johnson announced that London and the south-east of England would be subject to tighter COVID-19 restrictions to contain the variant, which Johnson said could be 70% more transmissible. Although there is no evidence yet that the tension is deadlier, many countries have closed their borders to travelers from the UK as they reflect on how to deal with the possible new threat. Several announced that they also had the variant among their populations.
Like this number of Science went to press on December 23, scientists were still trying to figure out if the variant is really spreading faster, and if so, how. But its emergence had given rise to the idea that viral evolution, which so far has had little impact on the trajectory of the COVID-19 pandemic, could still lead to unpleasant surprises – just as the first effective vaccines are being deployed. It also raises the question of whether these vaccines may require periodic updating to ward off an evolving virus.
The British SARS-CoV-2 line has apparently acquired 17 mutations that lead to amino acid changes in its proteins at the same time, a feat never seen before in the coronavirus. Importantly, eight of them were in the gene that encodes the peak, a protein on the viral surface that the pathogen uses to enter human cells. “There is now a frantic push to try to characterize some of these mutations in the laboratory,” says Andrew Rambaut, molecular evolutionary biologist at the University of Edinburgh.
Three are already worrying. A mutation called N501Y has previously been shown to increase the way the peak binds to the angiotensin-2 converting enzyme receptor, its primary entry point into human cells. Scientists in South Africa were the first to spot the importance of N501Y: they noted it several weeks ago in a burgeoning lineage in the provinces of the Eastern Cape, Western Cape and KwaZulu-Natal . “We have found that this line seems to spread much faster,” says Tulio de Oliveira, a virologist at the University of KwaZulu-Natal whose work alerted British scientists to the mutation. It’s worrying, says evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center: “Anytime you see the same mutation independently selected multiple times, it increases the weight of evidence that that mutation is likely to be beneficial. certain way for the virus.
The second notable mutation of B.1.1.7, a deletion named 69-70del, results in the loss of two amino acids in the spike protein. It had also appeared before: it was found, along with another mutation named D796H, in the virus of a COVID-19 patient in Cambridge, UK, who received plasma from recovered patients as treatment, but is ultimately deceased. In laboratory studies, the patient’s strain was less sensitive to convalescent plasma from multiple donors than the wild-type virus, says Ravindra Gupta, a virologist at the University of Cambridge who published the results in a pre-print in early December. .
Gupta also engineered a lentivirus to express mutated versions of the SARS-CoV-2 peak and found that the deletion alone made the virus twice as infectious to human cells. A third mutation, P681H, also needs to be watched, explains virologist Christian Drosten of Charité University Hospital in Berlin, because it changes the site where the spike protein is cleaved before entering human cells.
The N501Y mutation affects the amino acids (yellow) in the spike protein, which binds to a human receptor (green).
CREDITS: (IMAGE) COVSURVER ACTIVATED BY GISAID; (DATA) EMMA HODCROFT / UNIVERSITY OF BERN
New strains of virus are common in epidemics and often raise alarm bells, but few are ultimately significant. British scientists and others were therefore initially cautious in concluding that mutations in B.1.1.7 allowed the virus to spread better from person to person. But the new variant is quickly replacing other viruses, says Müge Çevik, an infectious disease specialist at the University of St. Andrews. Yet the exact impact of each mutation is much more difficult to assess than spotting them or showing that they are increasing, says Seema Lakdawala, a biologist at the University of Pittsburgh.
Animal experiments can help show an effect, but they have limits. Hamsters already transmit the SARS-CoV-2 virus rapidly, for example, which could mask any effects of the new variant. Ferrets transmit it less effectively, so a difference may be more easily detected, Lakdawala says. “But does this really translate to humans? I doubt it. ”A definitive answer can be months off, she predicts.
The multitude of mutations also raised concerns that the South African or British lineage could lead to more serious disease or even escape vaccine-induced immunity. So far, there is little reason to think so. While certain mutations have been shown to allow the virus to escape monoclonal antibodies, both vaccines and natural infections appear to lead to a broad immune response that targets many parts of the virus, explains Shane Crotty of the Institute. of La Jolla immunology. “It would be a real challenge for a virus to escape this.” The measles and polio viruses have never learned to escape the vaccines that target them, he notes: “These are historical examples suggesting not to panic.”
At a press conference on Dec. 22, BioNTech CEO Uğur Şahin pointed out that the UK variant only differs in nine of the more than 1,270 amino acids of the spike protein encoded by messenger RNA in the very effective COVID-19 vaccine that his company developed with Pfizer. “Scientifically, it is very likely that the immune response of this vaccine could also cope with the new virus,” he said. Experiments are underway and should confirm this soon, Şahin added.
Another major question is how the virus has accumulated a multitude of mutations at one time. So far, SARS-CoV-2 has typically only acquired one to two mutations per month. Scientists believe the new variant may have gone through a long period of rapid evolution in a chronically infected patient who then passed on the virus. “We know it’s rare, but it can happen,” says World Health Organization epidemiologist Maria Van Kerkhove.
Sébastien Calvignac-Spencer, evolutionary virologist at the Robert Koch Institute, says the new COVID-19 lockdown in the UK and the closure of borders to other countries mark the first time such drastic action has been taken on the basis of genomic surveillance in combination with epidemiological data. “It’s pretty unprecedented on this scale,” he says. But the question of how to respond to puzzling mutations in pathogens will arise more often, he predicts. Most people are happy to have prepared for a Category 4 hurricane even if the forecast turns out to be wrong, Calvignac-Spencer says. “It’s kind of the same, except we have a lot less experience with genomic monitoring than with weather forecasting.”
For Van Kerkhove, the arrival of B.1.1.7 shows how important it is to closely follow the viral evolution. The UK has one of the most sophisticated surveillance systems in the world, she says. “My concern is, how much is this happening in the world, where we don’t have sequencing capacity?” Other countries should step up their efforts, she said. And all countries should do what they can to minimize the transmission of SARS-CoV-2 in the months to come, Van Kerkhove adds. “The more this virus circulates, the more likely it is to change,” she says. “We are playing a very dangerous game here.”
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