How the UK became a world leader in Coronavirus genome sequencing

Viral sequencing – producing a kind of virus barcode – has emerged in recent months as crucial in the global hunt for versions of the pathogen that are best suited to infect humans, evade vaccines and possibly kill . Viruses first identified in the UK, South Africa and Brazil have caused concern among experts.

The variant discovered by sequencers in the UK, which is now the dominant variety in the country, has a mutation that seems more able to bind to human cells. Studies suggest that it is 50% more transmissible than the previous prevalent variant, while other research suggests that it could be at least 30% more lethal.

New viral variants are more likely to be seen in the UK than elsewhere. As of January 29, the UK has deposited 44%, or about 190,000, of its genomes in a global library led by the global nonprofit initiative on sharing all data on influenza or Gisaid. This represents about 5.1% of the almost four million cases detected 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, which means that scientists’ understanding of where and how the virus moves is uneven.

This is a weakness of the global response to the pandemic: the rapid detection of new variants allows governments to adjust restrictions and limit travel to countries where new annoying variants predominate. It can also help vaccine developers update their vaccines.

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

Half of the genomic sequences in the UK were generated at the Wellcome Sanger Institute, a Cambridgeshire facility that stores, sorts, samples and sequences genomes from the by-products of Covid-19 positive tests at five major UK laboratories.

The US has increased its contribution to the global coronavirus genome database since December and has so far added 20% of the total. It assessed approximately 0.3% of US Covid-19 cases.

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

Britain’s capabilities are partly built on history. British scientists have discovered the double helix DNA and were part of the international team that first sequenced the human genome.

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

The state-run, state-run national health service is also closely linked to an extensive network of researchers from its universities and the pharmaceutical industry.

However, large-scale sequencing of coronavirus in the UK has hardly begun.

On March 4, when Britain learned of four cases of Covid-19, microbiologist Sharon Peacock called a group of other scientists who agreed with her that sequencing the virus’s genome to monitor mutations would be vital for monitor its spread throughout the country and identify the source of the outbreaks.

They met with opposition. Some scientists have found that large-scale genome sequencing of a virus that moves more slowly than others, such as the flu, would be useless.

“At the time, there were people who said that there would not be enough mutational difference to make this useful,” said Dr Peacock, who is now director of Covid-19 Genomics UK, a network set up to track the family tree of coronavirus.

On March 11, the same day that 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, human genome sequencing experts and vaccinologists, to eliminate a plan for large-scale coronavirus sequencing.

“It wasn’t like a standard scientific meeting, it was a huge debate about how we could do that,” Dr. Peacock recalled. By the end of the day, they had a plan and sent it to England’s chief scientific officer on March 18. It was also accepted 20 million pounds, the equivalent of 27 million dollars, from government funds were granted on April 1 for the establishment of COG-UK.

“This has been the rhythm of perfection and it has been so since then, but I am delighted that our consortium of over 600 people can contribute to our understanding of the diseases,” she added.

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

The scale of genomic sequencing production in the UK – which assessed up to 10% of all positive coronavirus tests in the UK at certain times in the pandemic – was intended to identify over-spreading events in which identical sequences occur, closely related to predecessors. their. same time.

When an RNA virus like the one causing Covid-19 reproduces inside a new host, mistakes can be made in its genetic code. Most don’t matter, some are corrected and corrected and sometimes no mistakes are made. But some of the errors or mutations are numerous or important in changing the virus to affect its biology, giving it, in rare cases, an advantage over its predecessors.

Coronaviruses move more slowly than other viruses, such as the flu, so initially scientists did not think there would 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 move. Some changes, including one in the British version now reported in at least 64 countries, give evolutionary advantages over their predecessors, which make the virus version more transmissible.

The new variant came to the attention of experts in November, when a version with a large number of significant changes compared to its predecessor began to accumulate in a corner of the south-east of England, creating an outcrop of identical genomes that turned red on genomists’ screens.

Initially, the sequencers did not know if the variant was gaining prominence due to a widespread violation of coronavirus restrictions or if it was the cause of a new case, Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome Sanger Institute, said in a statement. online seminar this month.

By the last week of November, it became clear that in exactly the same place the mutant genomes were gathering, Covid-19 cases were accelerating in the community, despite the observance of a national blockade.

Going back through the genome databases, the sequencers found the first appearance of the highly mutant variant on September 20 in Kent, in the south-east of England, and another one a day later in London. The geographical correlation of the cases with the genomes allowed the virus detectives to say with a high degree of certainty that the correlation was not a coincidence and designated the virus as a matter of concern.

Write to Joanna Sugden at [email protected]