When British scientists rushed to set up a system to track the evolution of the coronavirus early last year, they faced doubts that it would be worth the effort.
In the initial months of the crisis, the pathogen appeared to be undergoing limited, inconsequential change. Each genome analyzed by the U.K. operation looked similar to the last, and even specialists in the field were somewhat skeptical.
“People actually thought it was a bit of a waste of time,” said Nick Loman, a University of Birmingham professor of genomics and bioinformatics who helped launch the project. “There was an element of ‘you’re doing very expensive stamp collecting here while there’s a pandemic going on.’”
Since then, dangerous variants surfacing in England, South Africa and Brazil have erased any questions about the organization’s value. Other countries are racing to catch up in sequencing, and the administration of U.S. President Joe Biden this month announced it will spend nearly $200 million to follow variants with stepped-up scrutiny from the U.S. Centers for Disease Control and Prevention.
The COVID-19 Genomics U.K. Consortium has become a global model for analyzing genomes for signs that the coronavirus is gaining power to spread — or to kill. More scientists are watching to see if new versions can evade vaccines from Johnson & Johnson, AstraZeneca PLC, Moderna Inc. and partners Pfizer Inc. and BioNTech SE that the world is counting on as the global death toll climbs past 2.5 million.
Led by University of Cambridge microbiologist Sharon Peacock, the U.K. group plans to expand training for everyone from lab technicians to policy makers in a bid to boost worldwide monitoring. As the virus spreads, the worry is that some regions will lack not only vaccines, but the ability to detect mutations that might undermine immunization campaigns everywhere.
Eyes on the virus
“We haven’t got eyes on the virus in many parts of the world,” Peacock said in an interview. She fears a future in which “the world is divided into two: places that don’t have any information about the virus, don’t have full access to vaccination and have a high burden of disease,” and everyone else.
COG-U.K., as the program is known, was rooted in early discussions with U.K. Chief Scientific Adviser Patrick Vallance and came together in a matter of weeks as Peacock called on Loman and other scientists for help. They received an initial £20 million ($28 million) in government funds.
The researchers analyze samples from COVID-19 patients in regional labs and the Wellcome Sanger Institute south of Cambridge. The pace is staggering at about 30,000 SARS-CoV-2 genomes sequenced each week, triple that of a couple of months ago. That’s more than twice the rate in the U.S., even after a massive boost at the CDC by Director Rochelle Walensky, who took over last month.
So far, COG-U.K. has contributed almost half of the coronavirus sequences shared with a global database called GISAID. The vast majority of changes in the virus are benign, but a few have set off alarms.
Burst of evolution
In early December, despite tougher restrictions, infections surged around London and Kent in southeast England. The U.K. program’s scientists noticed something unusual: At least half of the viruses causing the cases looked very similar genetically.
A group of accumulated changes in this version of the virus stuck out from the rest of the data in the family tree, according to Birmingham’s Loman, signaling a “burst of evolution.” Further analysis showed the variant was much more transmissible than earlier strains. What’s more, it was on the move to other parts of the country.
Six days before Christmas, Prime Minister Boris Johnson tightened controls on movement and travel, and “with a heavy heart” warned of the new and more contagious variant, called B.1.1.7. Before long, it had spread to more 50 other nations, including Japan, the U.S., Australia, Germany and Singapore.
Mutations that arose in South Africa and Brazil meanwhile have shown an ability to diminish — though not overcome — the potency of vaccines. That’s raised the profile of companies such as U.K.-based Oxford Nanopore Technologies that make equipment for sequencing viruses.
The work in the U.K. “is hugely under-recognized,” said Gordon Sanghera, chief executive officer of Oxford Nanopore. “The virus is going to mutate and move around. Those countries that heavily sequence find this stuff. You need to know what it is, and you need to move quickly.”
Despite its efforts in tracking the virus and securing vaccine, the U.K. has the highest death toll in Europe after missteps earlier in the pandemic, for which the government has faced intense criticism. With new cases dropping and the vaccine rollout progressing swiftly, Johnson has declared the end of the outbreak is in sight and set out a plan to ease lockdown rules.
While understanding among scientists of the virus has increased considerably, there’s still a lot to learn about its evolution as the focus turns to possibilities such as recombinations. These can occur when two different viral genomes co-infect the same host cell and exchange genetic material.
“The next few months of observing the way the virus is evolving is going to be critical,” said Peacock. She and her colleagues hold more than 50 Zoom calls a week as they track the virus, “keeping an eye on a constellation of mutations that appear to change the biology quite significantly.”
Rest of time
The Cambridge scientist and her team are seeking to make their collaboration with a couple of dozen countries more formal and integrate the effort into the U.K.’s public health agencies to maximize its impact.
“We will need this for the next pandemic,” she said.
Wealth isn’t necessary to track viruses, according to Loman. Congo is in a relatively strong position because of its experience monitoring Ebola. But in the future, having a strong genomic sequencing system won’t be enough, according to Jeremy Farrar, director of Wellcome, the U.K.-based health research foundation.
Surveillance must be linked to “public-health responses in order to be able to understand it,” he said. “Otherwise you’ll have thousands of variants, which if you don’t have the epidemiological data, will be impossible to interpret.”
Meanwhile, vaccine developers are preparing to revamp shots to respond to emerging variants if necessary and grappling with a new set of uncertainties. The possibility that the world will need shots at regular intervals, just like influenza vaccines that require annual reformulation, is becoming increasingly real.
“Monitoring for new ones and trying to contain the ones you have the most concern about will probably occupy us for the next year,” Loman said. “It might become like flu and occupy us for the rest of time.”
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