Hunting for COVID-19 variants

Towards the middle of December, a sombre Matt Hancock, UK Health Secretary, stood up to deliver an address to the House of Commons.

“Over the last few days, thanks to our world class genomic capability in the UK, we have identified a new variant of coronavirus, which may be associated with the faster spread in the south-east of England,” he told MPs.

It was the news that no one wanted to hear, yet which anyone who understood virus evolution might have anticipated. At the time, around 1,000 cases of infection with the new variant – dubbed the ‘Kent variant’ – had been identified. Just two months later, Professor Sharon Peacock, from Cambridge’s Department of Medicine, would tell the BBC that the variant had “swept the country", and was likely to spread worldwide.

If anyone was well placed to observe this sweep, it was Peacock. She leads the COVID-19 Genomics UK (COG-UK) Consortium, set up early on in the pandemic to deliver large-scale genome sequencing of SARS-CoV-2 to Public Health Agencies, the NHS and the UK government. COG-UK scientists together with Public Health England had been the first to realise that a variant first detected in Kent was rapidly establishing itself as the dominant variant in the UK.

This was not the first time that a variant had emerged and then spread rapidly.

“A variant first detected in Spain rapidly spread to many European countries over the summer months, and we were worried that it may be more transmissible,” explains Peacock, pulling up a slide that showed the SARS-CoV-2 lineages circulating in the UK since the start of the pandemic.

“If you look at the number of cases that we observed, there was a rapid surge in this variant in the UK – to the point where it became our most common circulating variant. But detailed analysis indicated that this pattern was most likely due to holiday travel.”

The Kent variant – known technically as B.1.1.7 – was different, however. Public health officials were seeing a surge of cases in Kent during a period of lockdown, while elsewhere in the UK numbers were stable. “That started to set alarm bells ringing,” she says.

When COG-UK scientists looked at the sequence data of this new variant, they saw that it had 23 differences in its genetic code compared to the original virus. Returning to the slide, Peacock points to a part of the virus ‘family tree’ that is based on comparing genomes with each other, pointing out what looks like an outlier, a distant, exotic relative – B.1.1.7. “It’s striking that it was clearly genetically different from other circulating SARS-CoV-2 in the UK.”

Looking back through their samples, they discovered that the first case of B.1.1.7 had appeared on 20 September 2020. For a while, there had been only a smattering of cases: it was only when this lineage began to expand towards the end of November and beginning of December that it became clear something was wrong.

World-leading expertise

Although COG-UK had been busy since day one, the consortium truly captured people’s attention with the emergence of the Kent variant. This, after all, was why COG-UK had been set up in the first place. Today, barely a day goes by without Peacock speaking to the media – both national and, increasingly, internationally.

While arranging one of these interviews, I had a chance to speak to a journalist in the USA who spoke rapturously about the consortium, astonished – almost angry – that her home nation seemed to be lagging way behind the UK when it came to genomic surveillance. As of mid-March 2021, COG-UK scientists have sequenced more than 350,000 virus samples, contributing just under half of all global SARS-CoV-2 sequence data deposited in GISAID, a major international open-access database.

When I ask why the UK is so far ahead, Peacock says she has puzzled over this for some time, but can only really say why she believes the UK is itself so strong (‘world-leading’, though she rarely uses this phrase herself). It is down to a combination of factors, she says.

Part of the reason is historic. The UK was an early adopter of using pathogen sequencing for public health. Every time a patient is diagnosed with TB, for example, their infecting organism is sequenced as a matter of routine, and the information is used to predict drug resistance and to look for TB outbreaks.

Then there is the matter of expertise. The UK has a large number of world experts in pathogen genomics, several of whom – such as Professor Ian Goodfellow at Cambridge – have worked on previous global emergencies, including the Ebola outbreak in West Africa. The UK also has strong networks of labs, including NHS labs, those of the four Public Health Agencies, and the Lighthouse Labs set up in response to SARS-CoV-2, as well as sequencing capability across regional labs and the Wellcome Sanger Institute.

Crucially, the information generated by these endeavours is shared, not squirrelled away for professional or commercial gain. “There's a philosophy that we give everything away. We give away all of our data, our methods and protocols. There are no egos in the room to stop that from happening.”

Despite being the Director of COG-UK and its driving force, Peacock feels uncomfortable when journalists give her too much credit. Referring to an article written in a major UK newspaper, she says, “I cringed when I read that Ravi [Gupta] and Ian [Goodfellow] were members of my group, since they are far more senior than this. They are independent PIs leading their own research teams.”

The autonomy of COG-UK researchers is important to the consortium’s success. “The way that the network was put together, it's a cooperative where we work together to contribute to the whole. [Our collaborators] work with us because they want to, and because it's important to the country. There's about 400 people in the network, and many of those people have volunteered.”

Much of what has been achieved has been done at no extra cost to the public purse. Nearly all of the COG-UK funds have been channelled into the costs of viral sequencing. Most of the collaborators are not paid by COG-UK funds, but instead are supported by their institutions. Rather than billing COG-UK for their researchers’ time and overheads, these institutions have essentially let their researchers work for free.

“Universities across the country have contributed hugely,” she says. “That's a staggeringly generous situation. [I want to] thank everybody, thank the universities, and thank people for their dedication. I think that universities don't really get enough of a shout out from all of this, but they have been utterly supportive of us.”