Monday , March 1 2021

How British scientists have found a more infectious version of the coronavirus

The coronavirus seemed to change immediately.

For months, Dr. Stephen Kemp, an infectious disease expert, scanned the global library of coronavirus genomes. He studied how the virus mutated in the lungs of a patient who was trying to shake off a violent infection at a nearby Cambridge hospital, and he wanted to know if these changes would occur in other people.

Then, in late November, Kemp made an impressive match: Some of the same mutations found in the patient, along with other changes, reappeared again and again in new infected people, mostly in the UK.

Worse, the changes were concentrated in a protein that the virus uses to attach to human cells, suggesting that the virus, which has already caused chaos around the world, has evolved in a way that could make it even more contagious.

“There are a lot of mutations that occur with the same frequency,” he wrote on December 2 to Dr. Ravindri Gupti, a Cambridge virologist. Enumerating the most disturbing changes, he added: “ALL of these sequences have the following mutants with spikes.”

Both researchers did not yet know this, but they found a new, highly contagious version of the coronavirus, which has since been stamped across Britain, shaking scientists’ understanding of the virus and threatening to halt global recovery from the pandemic.

The word flew through a consortium of British disease scientists, longtime torchbearers in the field of genomics, who helped track the Ebola and Zika epidemics. They gathered for Slack and video calls, comparing notes, chasing clues – among them a clue from scientists from South Africa about another new option there. Since then, others have appeared in Brazil.

For almost a year, scientists have observed only gradual changes in the coronavirus and expected the same. New options have forced them to change their minds, heralding a new phase of the pandemic, when the virus could develop in time to undermine the effectiveness of vaccines.

British lawmakers announced the news on December 14, warning that the option is spreading faster than the previous ones.

But the road to its discovery was paved by weak recognition in March, when Britain decided to begin mass sequencing of coronavirus samples. The country produces half of the world’s coronavirus genomes, providing an unprecedented view of how the virus is changing and how people brought it to Britain last year, and they are now implementing it.

For Britain, the discovery came too late to prevent a punitive new wave of COVID-19, which put its hospitals on the verge of refusing rescue assistance. The option was already spreading rapidly, supporting the government’s sluggish restrictions in the fall and early winter.

But Britain has sounded the alarm for the world, allowing countries to close their borders and start frantically looking for an option they might not otherwise have noticed for months. British scientists quickly published studies that convinced skeptics of its potential.

“The UK is wrong about this pandemic – mainly by not learning the lessons of the importance of early response,” said Neil Ferguson, a public health researcher and government adviser. “But the UK has a very unsurpassed COVID surveillance system. We can track very small changes in the virus. “

Laboratories around the UK, after testing for swabs for the virus, send the remnants of the material in refrigerated vans to the Wellcome Sanger Institute of Gelcomics, where they are stored in cavernous freezers.

There, the works separate the positive samples and deposit them in a well of tiny plates, similar to cupcakes. The machines then map their genomes, said Jeffrey Barrett, who runs the sequencing project, producing 30,000 letter-length genetic codes that are uploaded to an online library. The task of understanding mutations lies with biologists such as Andrew Rambo, a professor in Edinburgh, who determine where they are located on the evolutionary tree.

These efforts have created more than 165,000 sequences in the UK. The United States, where it is five times the number of people, was followed by about 74,000 genomes. Germany followed about 3,400, less than half of what Britain uploaded to the global database on Thursday alone.

“It has completely changed our fight against the virus,” said Judith Breuer, a virologist at University College London.

The campaign took place on March 4, before 100 coronavirus infections were detected in Britain, when Cambridge microbiologist Sharon Peacock sent British letters to British genomists, asking everyone, “Can you call me, please?”

Within two weeks, their newly formed consortium secured state funding of £ 20 million, about $ 27 million.

“There is a close community here, and in March it actually rejected any rivalry, any ego, and simply said, ‘We can play an important role in managing a pandemic,'” said Thomas Connor, a Welsh scientist who created the platform for collection and analysis of genomes.

Among the samples taken last summer were samples from a 70-year-old man with lymphoma who was admitted to a Cambridge hospital in May for treatment with COVID-19. Gupta, a part-time doctor, began treating a patient whose anti-cancer drugs had depleted his immune response. Protected in solitary confinement, the patient tried to breathe. Even after several rounds of treatment, including plasma with antibodies from recovered patients, the virus did not disappear.

Instead, he mutated. British sequencing efforts have opened the window to these changes: During the 101-day hospital stay, viral particles seeped into the human lungs through a sequence of 23 times, a treasure trove of clues.

The patient died in August, apparently without infecting anyone else. But mutations in his virus eventually provided scientists with a leading theory of how the British version emerged: by avoiding the immune defenses of someone like a Cambridge patient who had a weakened immune system and a long-term infection.

“We call this the gold standard patient for assessing different viral populations in the host,” Kemp said.

One mutation in a patient, designated 69-70del, changes the shape of the adhesion protein. Another, N501Y, can help the protein bind more closely to human cells.

Kemp searched for these changes every few days in a global database, finding rare causes for concern. Then, in late November, he suddenly noticed many genomes, mostly British, that had those mutations and many others that could change the way the virus entered human cells. He called Gupta to his computer to look.

Eventually, British scientists discovered 23 mutations that distinguished these genomes from the earliest known version in Wuhan, China – enough to consider it a new variant, as it is referred to as B117. On the evolutionary tree made by Kemp, it stood alone as a solitary, spindle branch.

“I didn’t expect anything like that,” Gupta said. “Back in late November, everything was linked to the hope of a vaccine, and no new options were observed.”

The number of mutations in the adhesion protein particularly shocked him, he said, calling it a “wow” moment.

At the same time, British health experts were surprised by the inexplicable outbreak of coronavirus cases. The blockade has hardened the virus across England, but not in Kent, London’s London, which travels on roads and orchards in the south-east. There were cases in schools. Each of the 328 residents was infected.

It was not until December 8, at their next meeting with genomists, that health officials concluded that the reason was probably a new option. Examining their databases, the researchers found that it was first collected in September and distributed when people returned to offices and patronized restaurants and pubs at the urging of the government.

In the end, the researchers found that this option was actually more transmissible – about 30-50% more – but only after they collected a piece of less clear clues.

“There is no absolutely unequivocal evidence; science only generates such a guarantee over long periods of time, ”said Oxford evolutionary biologist Oliver Peabus. “It was more about different independent sets of evidence.”

After scientists presented their opinion to a government advisory body on December 11, Ferguson, a health researcher, was concerned that he would “almost certainly require another blockade from us.” He emailed Prime Minister Boris Johnson’s chief scientific adviser warning of the option.

By December 22, government scientists said that austerity measures, including school closures, were needed to suppress the option. But Johnson allowed people in some parts of England to gather for Christmas and did not impose an all-English blockade until 4 January.

It is now estimated to account for more than 80% of positive cases in London and at least a quarter of infections elsewhere in England, and has been found in more than 50 countries. U.S. health officials warned on Friday that the British variant could become the main source of infection in the United States by March.

In recent days, Gupta and Kemp have begun using serum from vaccinated people to determine if this option could reduce the effectiveness of vaccines.

“For a long time, people around the world said that mutations in the coronavirus didn’t really matter,” Gupta said. “But we found that the mutations did come, and they affected the viability of the virus.”

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