The battle against Covid-19 is truly global.
But in one area the UK is the undisputed world leader — tracing the genetic profile of the virus as it mutates around the world.
There are now four "variants of concern" of the virus that causes Covid-19 identified by government advisers. Three have been found in Britain, and the fourth is the Brazil variant identified in people who had travelled to Japan.
Yet if it wasn’t for the Covid-19 Genomics UK (COG-UK) consortium, such mutations would have likely remained undiscovered, spreading silently in the population.
Since March, the UK has sequenced around ten times as many Covid-19 genomes as the world’s next best sequencers, with around 50pc of all genome testing of Covid done in the UK, equal to just over 250,000 genomes.
“I’d say what we’re doing is critical right now,” says Dr Ewan Harrison, director of strategy and transformation at COG-UK. “We’re really providing the intelligence that’s going to allow us to change the vaccines if we do need to. We’ve got the data about which parts of the virus are mutating and then we can respond.”
Together, a group of around 400 scientists across more than 30 UK institutions and universities have been working to develop a world-class genome sequencing network, focused on tracking the virus and its various strains in real-time.
Viruses mutate all the time and most changes do not cause a problem, scientists insist. But every so often a virus mutates in a way that benefits it, for example allowing it to spread more quickly or to bypass immunity, and causes us to be concerned about changes in the way the virus might behave.
To track these changes, COG-UK scientists send Covid-19 tests to labs, where samples are taken and placed in machines which analyse their components and show how it is formed, allowing scientists to see which strain it is.
These results are then placed in a nationwide database, along with where they came from in the country, essentially forming a real-time video feed of where cases are emerging and which strain they are.
At the start of the pandemic, they helped map where the virus was coming from internationally, as different countries had different strains.
It was something researchers were adamant would be important. “Back in the beginning of March, we really realised that sequencing was going to be a key tool in the fight against the virus,” Sharon Peacock CBE, chair of COG-UK says.
“A group of genetic experts got together, and we spent the whole day thinking about what a sequencing network would look like, where would it be, and really hashed out the blueprint for it.”
Within days, the group had written a proposal and put it on the desk of Sir Patrick Vallance, the government chief scientific adviser. “We got funding by the first of April. And that’s where our story really begins.”
That may be where the story begins, but its origins were much earlier. The UK has a long legacy in genetics, having been where DNA was discovered, paving the way for an explosion of research into the industry and leading to the formation of research institutes such as the Francis Crick Institute in London and the Wellcome Sanger Institute, named after Fred Sanger, famous for work decoding DNA.
More recently, years worth of grants and work by various research university groups formed the groundwork for the COG-UK network, looking specifically into how viruses can be tracked.
The Artic Network, for example, had received funding from the Wellcome Trust, having said that pathogen surveillance would need to be in place, and having conducted work on Ebola and Zika.
Another, the Oxford Martin School program on pandemic genomics, had travelled to South America during the Zika virus, using a mobile lab and technology by Oxford-based Oxford Nanopore to sequence the virus.
“We knew from our previous work on other outbreaks that we could learn a lot about an epidemic by sequencing and analysing the genomes of the virus,” says Dr Oliver Pybus, a professor of evolution and infectious disease at the University of Oxford.
Here, with the Covid-19 virus, the vast network of genetic scientists have been undertaking surveillance to try to map how the virus is spreading and changing, taking Covid-19 tests from across the country and working out which strains are where.
Alongside that core work, they have been working on targeted sequencing, looking at cases where people have had a severe form of the illness or have been reinfected, as well as recently taking and sequencing tests from areas undergoing “surge testing” such as Maidstone.
Getting the network to this scale has been no mean feat — but, Peacock says, the plan is for it to scale further. “We’re sequencing around 27,000 genomes a week. What we’re moving towards is a situation where we were sequencing the same amount in one or two weeks, as we used to be doing in a year.”
The reason being “we need to have eyes on the genomes in order to understand how to vaccinate our population and also how to maximise our public health interventions”.
COG-UK works closely with modelling teams to help estimate whether particular lineages are more transmissible, as well as researchers who put together detailed records about patient disease and outcome to estimate severity.
Work around this has come to the fore in recent weeks, as various strains have appeared more transmissible and others, potentially, more able to evade immunity. The Kent variant, which first was identified in the south east of England in September, for example, is now the dominant strain in the UK given its higher transmissibility.
A variant which was first identified in South Africa, meanwhile, may have mutated to attempt to bypass immunity, according to a study from scientists in the country.
Where have cases of the South African variant been detected? (Feb 10)
Scientists say there are likely to be many other strains, although other countries which have less advanced sequencing networks may not have identified them.
“You only find what you look for," says Peacok. "Because we’re doing so much sequencing, I think that’s why we’re detecting them. It’s quite likely that variants are arising elsewhere in the world. The question is, how many more fresh mutations will arise that we actually start to care about.” These would be in areas such as transmissibility or to survive immunity.
The latter is expected to become increasingly common as vaccination efforts continue. As the virus evolves and more people become immune, “it’s no longer just trying to get to new people as fast as possible”,” says Pybus. “If a lot of people are already immune, then it can’t reach and affect them. So then what we would expect is more mutations that allow the virus to escape immunity.”
The UK’s expertise in this area puts it at an advantage in helping stem the virus — one which, it is becoming increasingly apparent, will need to be shared with other countries. Late last month, the UK launched its New Variant Assessment Platform, which opened the door up to other countries to send samples for sequencing, or provide advice to companies which have some capabilities.
“We’ve demonstrated that we picked up the UK variant quite early on,” says Harrison. “Our network is working, what we need now is globally the same thing.” After all, he says, “wherever we get transmission, you risk mutation.” And if other places aren’t sequencing as much as the UK, then the risk of mutation could be with us for some time. “You just can’t be sure.”
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