ScienceCOVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation.
Trucks en route to France line up in southeastern England on December 21, 2020, after the border was closed in an attempt to prevent the spread of a new variant of SARS-CoV-2.
PHOTO: DAN KITWOOD / GETTY IMAGES
On December 8, 2020, a small group of scientists in the UK connected for a regular video conference on Tuesday about the spread of the pandemic coronavirus. The discussion focused on Kent, a county in southeastern England that was seeing an increasing transmission of SARS-CoV-2, even as the rest of the country managed to stem the spread. As the investigations found no obvious cause – no major outbreak in the workplace or changes in people’s behavior – several researchers were asked to examine the region’s viral genomes.
Their genetic family tree showed that something unusual was going on, said 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 branching literally stood out from the rest of the data. “I’ve never seen a part of the tree that looked like this before,” says Loman. And when scientists compared how quickly this variant, called B.1.1.7, and others were spreading, they made an astonishing discovery: the virus appeared to have become more adept at transmitting between people.
The discovery of the viral lineage, along with another equally worrying one in South Africa, had a huge impact. On December 19, UK Prime Minister Boris Johnson announced that London and south-east England would be placed under stricter COVID-19 restrictions to contain the variant, which Johnson said may be 70% more transmissible. While there is still no evidence that the strain is more deadly, many countries have closed their borders to UK travelers while reflecting on how to deal with the possible new threat. Several announced that they also had the variant among their populations.
As this question of Science went to print on December 23, scientists were still struggling to understand whether the variant really spreads faster and, if so, how. But its emergence has brought to the fore the notion that viral evolution, which has so far had little impact on the trajectory of the COVID-19 pandemic, could still result in unpleasant surprises – just as the first effective vaccines are being launched. It also raises the question of whether these vaccines may need periodic updating to prevent a virus change.
The British strain of SARS-CoV-2 apparently acquired 17 mutations that lead to changes in amino acids in its proteins at once, a feat never seen before in the coronavirus. Crucially, eight of them were in the gene that codes for spike, a viral surface protein that the pathogen uses to enter human cells. “There is now a frantic impulse to try to characterize some of these mutations in the laboratory,” says Andrew Rambaut, a molecular evolutionary biologist at the University of Edinburgh.
Three already stand out as worrisome. A mutation called N501Y has been shown previously to increase how strongly the peak binds to the angiotensin-converting enzyme 2 receptor, its main entry point into human cells. South African scientists were the first to spot the importance of the N501Y: they noticed it several weeks ago in a strain that is emerging in the Eastern Cape, Western Cape and KwaZulu-Natal provinces. “We found that this strain seems to be spreading much faster,” says Tulio de Oliveira, a virologist at the University of KwaZulu-Natal, whose work has alerted UK scientists about the mutation. This is worrying, says evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center: “Whenever you see the same mutation being selected independently several times, the weight of the evidence that this mutation is probably beneficial in some way to the virus increases. ”.
The second notable mutation in B.1.1.7, a deletion called 69-70del, leads to the loss of two amino acids in the peak protein. It had also appeared before: it was found, along with another mutation called D796H, in the virus of a COVID-19 patient in Cambridge, UK, who received plasma from recovered patients as treatment, but eventually died. In laboratory studies, the patient’s strain was less susceptible 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 prepress in early December.
Gupta also designed a lentivirus to express mutant versions of the SARS-CoV-2 peak and found that exclusion alone made the virus twice as infectious to human cells. A third mutation, P681H, should also be seen, says virologist Christian Drosten of Charité University Hospital in Berlin, because it changes the location where the spike protein is cleaved before entering human cells.
The N501Y mutation affects the amino acids (yellow) in the protein spike, which binds to a human (green) receptor.
CREDITS: (IMAGE) COVSURVER ENABLED BY GISAID; (DATA) EMMA HODCROFT / BERN UNIVERSITY
New strains of viruses are common in outbreaks and often generate alarms, but few are consequential. Therefore, scientists in the United Kingdom and others were initially cautious in concluding that the B.1.1.7 mutations made the virus better at spreading from person to person. But the new variant is rapidly replacing other viruses, says Müge Çevik, an infectious disease specialist at the University of St. Andrews. However, exactly the impact of each mutation is much more difficult to assess than to locate or show that they are increasing, says Seema Lakdawala, a biologist at the University of Pittsburgh.
Animal experiments can help show an effect, but they have limitations. Hamsters already transmit the SARS-CoV-2 virus quickly, for example, which could obscure any effect of the new variant. Ferrets transmit less efficiently, so the difference can be detected more easily, says Lakdawala. “But does this really translate to humans? I doubt it. “A definitive answer could take months, she predicts.
The sheer number of mutations has also raised concerns that the South African or UK lineage could lead to more serious illnesses or even escape vaccine-induced immunity. So far, there is little reason to think so. While some mutations have been shown to allow the virus to avoid monoclonal antibodies, vaccines and natural infections appear to lead to a broad immune response that affects many parts of the virus, says Shane Crotty, of the La Jolla Institute for Immunology. “It would be a real challenge for a virus to escape this.” The measles and polio viruses never learned to escape the vaccines targeted at them, he notes: “These are historical examples that suggest not to freak out.”
At a press conference on December 22, BioNTech CEO Uğur Şahin pointed out that the UK variant differed by only nine from the more than 1270 amino acids of the spike protein encoded by the messenger RNA in the highly effective COVID-19 vaccine that his company developed with Pfizer. “Scientifically, it is highly likely that the immune response to this vaccine can also handle the new virus,” he said. Experiments are underway and should confirm this soon, added Şahin.
Another important question is how the virus accumulated a series of mutations at once. Until now, SARS-CoV-2 normally acquired only 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 transmitted the virus. “We know that this is rare, but it can happen,” says World Health Organization epidemiologist Maria Van Kerkhove.
Sébastien Calvignac-Spencer, an evolutionary virologist at the Robert Koch Institute, says the UK’s new COVID-19 blockade and the closure of other countries’ borders marks the first time drastic measures have been taken based on genomic surveillance in combination with data epidemiological factors. “It’s unprecedented on that scale,” he says. But the question of how to react to disconcerting mutations in pathogens will arise more often, he predicts. Most people are happy to have prepared for a Category 4 hurricane, even if the predictions turn out to be wrong, says Calvignac-Spencer. “This is somewhat the same, except that we have much less experience with genomic surveillance than with weather forecasting.”
For Van Kerkhove, the arrival of B.1.1.7 shows how important it is to follow viral evolution closely. The UK has one of the most elaborate monitoring systems in the world, she says. “My concern is: how much of this is happening globally, where we don’t have the capacity for sequencing?” Other countries should step up their efforts, she says. And all countries must do what they can to minimize the transmission of SARS-CoV-2 in the coming months, adds Van Kerkhove. “The more this virus circulates, the more opportunities it has to change,” she says. “We are playing a very dangerous game here.”