How the UK became the world leader in coronavirus genome sequencing

Viral sequencing – producing some sort of barcode for the virus – has become critical in recent months in the global hunt for versions of the pathogen that are more adapted to infect humans, evade vaccines, and potentially kill. Virus variants first identified in the UK, South Africa and Brazil have raised concerns among experts.

The variant that the sequencers discovered in the UK, which is now the dominant variety in the country, has a mutation that appears to bind better to human cells. Studies suggest it is 50% more transmissible than the previous common variety, while other research suggests it may be at least 30% more deadly.

New viral variants are more likely to be spotted in the UK than anywhere else. As of January 29, the UK had submitted 44%, or about 190,000, of the genomes into a global library of the nonprofit Global Initiative on Sharing All Influenza Data, or Gisaid. That’s about 5.1% of the nearly four million cases discovered in the UK

The US is rapidly expanding its sequencing capabilities – but only a handful of other countries have contributed more than 1% to the library, meaning scientists’ understanding of where and how the virus mutates is patchy.

That represents a weakness in the global response to the pandemic: rapid detection of new variants allows governments to adjust restrictions and restrict travel from countries where new troublesome variants are prevalent. It can also help vaccine developers update vaccines.

The UK says it plans to address that weakness by exporting its expertise to countries with limited sequencing capabilities.

Half of the UK genome sequences were generated at the Wellcome Sanger Institute, the Cambridgeshire facility that stores, sorts, samples and sequences genomes of positive Covid-19 test byproducts from five major UK laboratories.

The US has increased its contribution to the global coronavirus genome database since December, adding 20% ​​of the total so far. It has assessed about 0.3% of the Covid-19 cases in America.

Anthony Fauci, President Biden’s chief medical adviser on the Covid-19 pandemic, said on CBS Sunday that US authorities need to expand genomic surveillance to identify variants of the virus.

Britain’s capabilities are based in part on history. British scientists discovered the DNA double helix and were part of the international team that was the first to sequence the human genome.

“The UK was one of the first countries in the world to recognize the need for a viral genomic sequencing infrastructure and we made huge investments in it long before Covid emerged,” said Health Secretary Matt Hancock in a speech on Tuesday.

The data-rich, state-run National Health Service is also closely linked to an extensive network of researchers from universities and the pharmaceutical industry.

Nevertheless, the large-scale sequencing of the coronavirus in the UK almost never got off the ground.

On March 4, when the UK had four known cases of Covid-19, microbiologist Sharon Peacock called on the phone with a group of other scientists who agreed that sequencing the virus’s genome to monitor mutations is vital. would be to track its spread. country and identify the source of outbreaks.

They met with opposition. Some scientists thought that large-scale genome sequencing of a virus that mutates more slowly than others, such as influenza, would be pointless.

“At the time, there were those who said there wouldn’t be enough mutation difference to make this worthwhile,” says Dr. Peacock, who is now a director of Covid-19 Genomics UK, a network created to trace the coronavirus family tree.

On March 11, the same day the World Health Organization declared a global pandemic, Dr. Peacock held a meeting in London at the Wellcome Trust with 19 others, including clinical virologists, technologists, experts in human genome determination and vaccineologists, to develop a plan for large-scale coronavirus sequencing.

“It wasn’t like a standard scientific meeting, it was a huge debate on how to do this,” recalls Dr. Peacock himself. At the end of the day, they had a blueprint and submitted it to the Chief Scientific Officer of England on March 18. It was accepted and on April 1, £ 20 million, equivalent to $ 27 million, in government funding was awarded to establish COG-UK.

“This was pace over perfection and it has been since, but I am delighted that our consortium of more than 600 people can contribute to our understanding of disease,” she added.

Still, the country’s success in discovering variants appears to be due more to serendipity than strategy.

The UK genomic sequencing output scale – which has rated up to 10% of all positive coronavirus tests in the UK at some points during the pandemic – was designed to identify superspreader events involving identical sequences closely related to their predecessors, showing up at the same time.

When an RNA virus, such as the virus that causes Covid-19, replicates in a new host, errors can be made in the genetic code. Most don’t matter, some are proofread and corrected, and sometimes no mistakes are made at all. But some of the errors, or mutations, are many in number or important in altering the virus to affect its biology, giving it an advantage over its predecessors in rare cases.

Coronaviruses mutate more slowly than some other viruses, such as influenza, so initially scientists thought there wouldn’t be enough mutations to make large-scale genomic sequencing worthwhile.

But because the virus has infected so many people – more than 100 million worldwide so far – it has had many opportunities to mutate. Some changes, including one in the British variant now present in at least 64 countries, confer evolutionary advantages over their ancestors that make that version of the virus more transmissible.

The new variant came to the attention of experts in November, when a version with a host of significant changes from its predecessor began to pile up in a corner of South East England, creating an offshoot of identical genomes that flashed red on the screens of genomists.

Initially, the sequencers were unsure whether the variant was gaining prominence due to its widespread ignoring of coronavirus restrictions or whether it was causing a flare-up in new cases, Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome Sanger Institute, said this month in an online seminar.

By the last week of November, it became clear that at the very same spot the mutated genomes converged, Covid-19 cases in the community accelerated despite adhering to a national lockdown.

Searching the genome databases, sequencers found the first copy of the highly mutated variant on September 20 in Kent, south-east England, and another one in London a day later. The geographic alignment of cases allowed virus detectives to say with a high degree of certainty that the correlation was not a coincidence and the virus was labeled as a cause for concern.

Write to Joanna Sugden at [email protected]