How the UK became world leader in the order of the Coronavirus genome

Viral sequencing – which produces a kind of barcode for the virus – has emerged as very important in recent months in the global hunt for versions of the pathogen that are better adapted to infect humans, avoid vaccines and possibly kill them. . Virus variants first identified in the UK, South Africa and Brazil have expressed concern.

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

New viral variants are more likely to be noticed in the UK than elsewhere. As of January 29, the UK has submitted 44%, or approximately 190,000, of the genomes held in a global library by the non-profit Global Initiative on Sharing All Influenza Data, or Gisaid. This is about 5.1% of the nearly 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, meaning scientists’ understanding of where and how the virus mutates is spot on.

This is a weak point in the global response to the pandemic: the rapid detection of new variants enables governments to adapt restrictions and limit travel from countries where new troublesome variants occur. It can also help vaccine developers update vaccines.

The UK says it intends to address the weakness by exporting its expertise to countries with limited order of succession.

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

The US has increased its contribution to the global coronavirus genomic database since December, adding 20% ​​of the total so far. It accounted for about 0.3% of U.S. Covid-19 cases.

Anthony Fauci, president Biden’s chief medical adviser to the Covid-19 pandemic, told CBS on Sunday that U.S. authorities should extend genomic surveillance to identify variants of the virus.

Britain’s capabilities are based in part on history. British scientists discovered the double DNA helix 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 a viral genomic sequencing infrastructure, and we supported it with huge investment long before Covid came forward,” said Health Secretary Matt Hancock. Said in a speech on Tuesday.

The country’s computer-rich, state-run national health service is also closely linked to an extensive network of researchers in its universities and the pharmaceutical industry.

Nevertheless, the large-scale sequencing of the coronavirus in the United Kingdom has hardly come off the ground.

On March 4, when the UK had four cases of Covid-19, microbiologist Sharon Peacock called a group of other scientists who agreed with her that the genome of the virus to monitor mutations was essential to its spread. through the country and identify the source of outbreaks.

They resisted. Some scientists thought that large-scale genome sequencing of a virus that mutated more slowly than others, such as influenza, would be useless.

“At the time, there were people who said there would not be enough mutation difference to make it worthwhile,” says Dr. Peacock, who is now director of Covid-19 Genomics UK, a network set up to detect the coronavirus pedigree.

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 experts and vaccinators, to develop a plan for large-scale coronavirus sequencing.

“It was not like a standard scientific meeting, it was a big debate about how we could do it,” said Dr. Peacock remembers. At the end of the day, they had a blueprint and submitted it to England’s scientific chief on 18 March. It was accepted and on April 1, £ 20 million, equivalent to $ 27 million, was funded by the government to set up COG-UK.

“It was just perfection and has been the case ever since, but I am delighted that our consortium of more than 600 people can contribute to our understanding of diseases,” she added.

Yet it seems that the country’s success in discovering variants is more due to serendipity than strategy.

The scale of the UK’s genomic sequencing – that it rated up to 10% of all positive coronavirus tests in the UK at some point during the pandemic – was intended to identify events in the distributor where identical sequences, closely related to their predecessors, emerges The same time.

When an RNA virus like the one causing Covid-19 repeats within a new host, its genetic code may be erroneous. Most do not matter, some are proofread and corrected and sometimes no mistakes are made at all. But some of the bugs, or mutations, are large or important to alter the virus to affect its biology, which in rare cases gives it an advantage over its predecessors.

Coronaviruses mutate more slowly than some other viruses like flu, so scientists initially did not think there would be enough mutations to make large-scale genomic sequencing worthwhile.

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

The new variant came to the attention of experts in November when a version with a large number of important changes compared to its predecessor began to gather in a corner of the south of England, creating an outcome of identical genomes that on genomists’ screens flashed red.

Initially, the sequences did not know whether the variant gained notoriety due to widespread coronavirus limitations and whether in new cases it was the cause of flare-up, said Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome. Singer Institute, said in an online seminar this month.

By the last week of November, it became clear that exactly the same place where the mutant genomes congregate, accelerating Covid-19 cases in the community, despite adhering to a national exclusion.

Successors through the genome databases sequences found the first occurrence of the highly mutated variant on September 20 in Kent, in the south-east of England, and another day a day in London. The geographical adaptation of cases to genomes enabled the detectives of the virus to say with a high degree of certainty that the correlation was not accidental and identified the virus as of concern.

Write to Joanna Sugden at [email protected]