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All of a sudden, the coronavirus seemed to change.
For months, Dr. Steven Kemp, an infectious disease expert, analyzed a global library of coronavirus genomes. He was studying how the virus had mutated in the lungs of a patient who was struggling to shake off a raging infection at a nearby Cambridge hospital, and he wanted to know if those changes would occur in other people.
Then, at the end of November, Kemp made a surprising match: some of the same mutations detected in the patient, along with other changes, were appearing over and over again in newly infected people, mainly in Britain.
Worse yet, the changes were concentrated in the spike protein that the virus uses to cling to human cells, suggesting that a virus that was already wreaking havoc in the world was evolving in ways that could make it even bigger. contagious.
“There are a bunch of mutations happening together at the same frequency,” he wrote Dec. 2 to Dr Ravindra Gupta, a Cambridge virologist. Listing the most disturbing changes, he added, “ALL of these sequences have the following spike mutants.”
The two researchers didn’t know it yet, but they had found a highly contagious new variant of the coronavirus that has since permeated Britain, shook scientists’ understanding of the virus and threatened to delay the global resumption of the pandemic.
The news circulated through a consortium of British disease specialists, longtime genomics torchbearers who had helped track the Ebola and Zika outbreaks. They gathered on Slack and video calls, comparing their notes while searching for clues – among them, a council of South African scientists on another new variant there. Still others have emerged in Brazil.
For nearly a year, scientists had observed only incremental changes in the coronavirus and expected more of the same. The new variants forced them to change their minds, foreshadowing a new phase of the pandemic in which the virus could evolve enough in time to affect the effectiveness of vaccines.
British lawmakers broke the news on December 14, warning that the variant was spreading faster than previous ones.
But the road to its discovery received little acclaim in March, when Britain decided to start mass-sequencing coronavirus samples. The country produces half of the world’s inventory of coronavirus genomes, offering an unrivaled view of how the virus is changing and how people introduced it to Britain last year and are now realizing the variant .
For Britain, the discovery came too late to prevent a new wave of punitive COVID-19 that has put its hospitals on the verge of having to refuse life-saving care. The variant was already spreading rapidly, encouraged by the government’s lax restrictions in the fall and early winter.
But Britain has sounded the alarm bells for the world, allowing countries to close their borders and start frantically searching for a variant they might not have noticed otherwise for months on end. British scientists quickly published studies that convinced skeptics of its power.
“The UK got a lot wrong about this pandemic – mainly by failing to learn about the importance of responding early,” said Neil Ferguson, public health researcher and government adviser. “But the UK has a pretty unrivaled surveillance system for COVID. We can watch for very small changes in the virus. “
British labs, after testing swabs for the virus, send the leftover material in refrigerated vans to the Wellcome Sanger Institute, a genomics lab, where they are stored in cavernous freezers.
There, robots separate the positive samples and drop them into the wells of tiny muffin-shaped plates. The machines then map their genomes, said Jeffrey Barrett, who heads the sequencing project, producing 30,000 letter-length genetic codes that are uploaded to an Internet library. The task of making sense of mutations falls to biologists like Edinburgh professor Andrew Rambaut, who determine their place on the evolutionary tree.
The effort generated more than 165,000 sequences in Britain. The United States, with five times as many people, has sequenced approximately 74,000 genomes. Germany has sequenced around 3,400, less than half of what Britain uploaded to the global database on Thursday alone.
“It has totally revolutionized the way we treat the virus,” said Judith Breuer, virologist at University College London.
The campaign took shape on March 4, before 100 coronavirus infections were discovered in Britain, when Cambridge microbiologist Sharon Peacock sent an avalanche of emails to British genomists, asking them each: ‘Can you call me, please? “
Within two weeks, their newly formed consortium had secured £ 20million, or roughly $ 27million, in government funding.
“It’s a tight community here, and in March, she effectively put aside all rivalries, all egos, and just said, ‘We can play a vital role in managing the pandemic,'” Thomas said. Connor, a scientist in Wales who has built a platform to collect and analyze genomes.
Among the samples sequenced last summer were those from a man in his 60s with lymphoma, admitted to a Cambridge hospital in May for treatment for COVID-19. Gupta, a part-time clinician, began treating the patient, whose cancer drugs had exhausted his immune response. Kept in an isolation room, the patient had difficulty breathing. Even after several cycles of treatment, including plasma with antibodies from recovered patients, the virus did not go away.
Instead, he transferred. Britain’s sequencing efforts have opened a window to these changes: For 101 days in hospital, viral particles leaking into human lungs were sequenced 23 times, a treasure trove of clues.
The patient died in August, apparently without infecting anyone else. But mutations in his virus ultimately provided scientists with a leading theory about the origin of the British variant: by evading the immune defenses of someone like the Cambridge patient who had a weakened immune system and a long-lasting infection. duration.
“We call it the gold standard for assessing different viral populations in a host,” Kemp said.
A mutation in the patient, labeled 69-70del, changes the shape of the spike protein. Another, N501Y, can help the protein bind more tightly to human cells.
Kemp searched the Global Database for these changes every few days, finding rare cause for concern. Then, at the end of November, suddenly, he noticed many genomes, mostly British, that had these mutations and a host of others that could change the way the virus entered human cells. He summoned Gupta to his computer for a look.
Eventually, British scientists detected 23 mutations that set these genomes apart from the oldest version known in Wuhan, China – enough to be considered a new variant, since labeled B117. On an evolving tree made by Kemp, it stood apart like a lonely, slender branch.
“I didn’t expect anything like it,” Gupta said. “At the end of November, it was all about hope for vaccination, and there was no smell of new variants coming.”
The number of mutations on the spike protein particularly rocked him, he said, calling it “a ‘wow’ moment.”
At the same time, public health experts in England were perplexed by an unexplained outbreak of coronavirus cases. A lockdown had tempered the virus across England, but not in Kent, a county of London commuters and fruit orchards in the south-east. Cases are emerging in schools. One in 328 inhabitants was infected.
It wasn’t until December 8, during their regular meeting with genomics, that public health officials concluded that the cause was likely a new variant. Browsing through their databases, scientists found that it was first collected in September and spread as people returned to offices and frequented restaurants and pubs at the behest of the government.
The researchers were eventually persuaded that the variant was in fact more transmissible – around 30% to 50% more – but only after putting together a patchwork of less conclusive clues.
“There is no totally unambiguous line of evidence; science only generates this kind of guarantee over longer periods of time, ”said Oliver Pybus, an evolutionary biologist from Oxford. “Rather, it was a case of different and independent sources of evidence brought together.
After scientists presented their finding on Dec. 11 to a government advisory body, Ferguson, the public health researcher, expressed concern that it “would almost certainly force us to proceed with another lockdown.” He texted Prime Minister Boris Johnson’s chief science adviser, warning of the variant.
On December 22, government scientists said strict measures, including school closures, were needed to remove the variant. But Johnson allowed people in parts of England to congregate over Christmas and did not impose an England-wide lockdown until January 4.
The variant is now estimated to account for over 80% of positive cases in London and at least a quarter of infections elsewhere in England and has appeared in more than 50 countries. U.S. health officials warned on Friday that the British variant could be the main source of infection in the United States by March.
In recent days, Gupta and Kemp have started using blood serum from vaccinated people to determine if the variant could weaken the potency of vaccines.
“The world has long been told that coronavirus mutations don’t really matter,” Gupta said. “But we found that mutations did occur that impacted the physical form of the virus.”
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