Is the UK losing its world leading covid surveillance network just when it needs it most?BMJ 2023; 381 doi: https://doi.org/10.1136/bmj.p1157 (Published 07 June 2023) Cite this as: BMJ 2023;381:p1157
In early March 2020 a group of scientists set up the Covid-19 Genomics UK Consortium (COG-UK). The country had fewer than a hundred confirmed cases, and the idea of tracking pathogen variants in a pandemic was a minority interest pursued at a handful of UK academic departments.
In less than a month COG-UK was producing the first of many published papers and regular updates to the Scientific Advisory Group for Emergencies (SAGE) and the four UK public health agencies. It showed early on that the novel coronavirus had been imported into the UK at least a thousand times in the first quarter of 2020, most frequently from Spain and France, with only a tiny fraction from China. By the end of the year COG-UK had described a “genomic cluster” of cases in Kent: the early signs of the first SARS-CoV-2 variant of concern, alpha.
Within 18 months COG-UK had contributed one million genomic sequences taken from positive community tests around the UK, ultimately representing a quarter of all those collected globally by the Global Initiative on Sharing All Influenza Data and thereby playing a major role in identifying new variants of concern throughout the pandemic. (The largest previous dataset of real time genomic viral epidemiology during an epidemic was 1500 genomes from the west African Ebola outbreak in 2014.)
COG-UK is the undisputed leader of large scale novel coronavirus genomic sequencing, giving rise to a burgeoning global public health initiative, with a long term version now launched by the World Health Organization. It can justifiably claim to have helped turn the tables on the pandemic. But this leader now faces an uncertain future, its funding wrapping up just as the UK government, like much of the world, wants to move on from covid-19. Exactly how the decision to close down COG-UK was made will be part of the current covid-19 inquiry. For the moment, the question remains: what happens to routine sequencing when one emergency is coming to an end and the threat of the next one is unknown but ever present?
Whole genome sequencing is the ability to transcribe the genetic instructions that a pathogen requires to develop and maintain itself. Genomic sequencing was slow, laborious, and expensive when it was first developed in the 1970s in Cambridge, but the pandemic coincided with it becoming faster, easier, and significantly cheaper in a short period, says Matt Linley, senior director for analytics and forecasting at Airfinity.
While the genome sequence of the coronavirus responsible for the 2002 SARS outbreak took several months to complete and publish, Shanghai scientists famously sequenced SARS-CoV-2 from a 42 year old man in just two days in December 2019. This then became available to global researchers with no physical access to the virus itself when published in full on the US genetic sequence database GenBank the following month.
That sequence enabled quick thinking pharma companies to initiate research in vaccines. It also led to the swift development of the covid test RT-PCR (reverse transcription polymerase chain reaction), usable by public health laboratories from the end of January 2020. These enabled genomic surveillance scientists to track new variants—mutations caused by “typos” in the genetic sequence. By combining these findings with public health information on the location and timing of covid cases, it was possible to identify variants of concern, mutations that were extra transmissible or able to evade the immune system.
“Two practical issues—speed and scale—had limited the usefulness of genomics in the past,” says Mark Woolhouse, a member of the SAGE subcommittee SPI-M (the Scientific Pandemic Influenza Group on Modelling). “COG-UK pushed both of these things to the limit. It didn’t quite operate in real time, but it was fast: a two week lag from the sample to the sequence was the norm in the first year of the pandemic.”
Proving its worth
COG-UK was funded with £20m from a covid-19 rapid research response “fighting fund” established by the government’s then chief science officer, Patrick Vallance, and its chief medical officer, Chris Whitty, with support in kind from the Wellcome Sanger Institute. The collaboration brought together the four public health agencies supplying the genomic sequences with 17 existing sequencing sites and 134 genomic sequencing machines in UK academic departments and at the Wellcome Sanger Institute. Vital to its success was a shared data system that also incorporated anonymised patient data already in existence.
Within five days of the start-up, members of the COG-UK network had published a fully functional SARS-CoV-2 genome sequencing profile known as the Artic protocol. “These were scientists from multiple research groups and institutions, who had been working for a decade on how to apply pathogen genomics to public health interventions,” says Sharon Peacock, professor of public health and microbiology at Cambridge University and executive director and chair of COG-UK.
For the first time, “genomic data collection and analysis became a really important part of the public health toolkit, particularly for identifying new pathogens and new variants, and any signals that a variant might be more transmissible,” says Michelle Kendall, research fellow at the Health Protection Research Unit in Genomics and Enabling Data based at Warwick University.
Jeffrey Barrett, who was director of the Wellcome Sanger Institute’s Covid-19 Genomics Initiative until December 2021, adds, ‘‘Each new variant could be identified and assessed for its ability to spread, as well as its ability to evade an immune response either from a vaccine or a previous infection.” And the sheer volume of genomic sequencing the UK did, linked to its hospital admission records, enabled researchers to test whether one variant was more or less deadly than another. “There were only a handful of countries that reached this level,” says Barrett.
By April 2021, with this process fully established, COG-UK began to hand over the sequencing network, along with its methods and analysis tools, to the newly established UK Health Security Agency (UKHSA) with a plan to create a sustainable, long term, national sequencing service for use beyond the pandemic. In May 2021 the then prime minister, Boris Johnson, offered a detailed outline of a “Global Pandemic Radar” that would be up and running by the end of that year, involving “a network of surveillance hubs, built on UK health security expertise, with real time data sharing and rapid genomic sequencing and response.”1 An ambitious “100 Days Mission,” launched the following month, planned to put the UK at the forefront of what the Cabinet Office called “a global collaboration to build capabilities to have diagnostic tests, drugs and vaccines ready to be deployed globally within 100 days of a new pandemic threat emerging.”
While COG-UK slowly began winding down before officially concluding at the end of March 2023, the Global Pandemic Radar didn’t get beyond the planning stage. Last month, on 16 May, a “10 year science plan” unveiled by the UKHSA repeated a commitment to the 100 Days Mission, although without further details—with genomics playing a bigger role in “routine public health practice” in managing infectious diseases including tuberculosis, measles, and HIV.
A version of the Global Pandemic Radar appears to be emerging in Europe. WHO launched the International Pathogen Surveillance Network (IPSN) in May 2023, supported by the WHO Pandemic Hub—a German initiative based in Berlin and set up in September 2021, 18 months after COG-UK was established and five months after Johnson had announced that the UK would be the world leader in health security. UKHSA’s chief, Jenny Harries, attended the IPSN launch, although so far the UK does not appear to have a strategic role within it.
What remains of UK covid genomic surveillance is slight, involving only hospital patients where sequencing of samples is of sufficient quality. This coincides with a dramatic reduction in testing and monitoring of covid levels from April 2023, a year after the government issued instructions on “living with covid-19,” with WHO downgrading the virus from a global health emergency in early May.
But, lest we forget, the pandemic is not over.
There may be trouble ahead
The challenge of such a policy, with massively reduced surveillance, is exemplified by the recent potential threat of the omicron subvariant, XBB.1.16,3 dubbed Arcturus and detected in 33 countries. The UK’s 66 recorded cases up to 11 April led to concerns that this could be a massive undercount, as only a fraction of samples are now tested thoroughly.
The UKHSA emphasises that vaccination remains our best defence against future covid-19 waves. But the scaling back of genomic surveillance “means we are getting an extremely skewed and unrepresentative view of SARS-CoV-2 variants in this country,” says Lawrence Young, a virologist at Warwick University. “Without adequate genomic surveillance, it’s impossible to be certain whether Arcturus is more infectious, more pathogenic, and whether it affects vaccine immunity,” he tells The BMJ.
There is further confusion over the contribution of genomic surveillance to future pandemic preparedness. WHO’s list of potential public health emergencies of international concern comprises a diverse set of infectious diseases including Ebola, mpox, Zika, and polio, as well as a still unknown variant of covid-19.3
Vallance, speaking at the end of his term as the UK’s chief scientific adviser, said that the best option for pandemic preparedness was “surveillance on the lines of flu but with more genomic data”—which Peacock believes is “spot on.” But it’s far from clear how a routine genomic surveillance system will be able to identify an emergency and then mobilise swiftly and effectively in response to it.
The bottom line, says Mark Woolhouse, professor of infectious diseases epidemiology at the University of Edinburgh, is that “we need a range of pandemic response plans along with the ability to establish quickly which one is the right one for the emergency at hand—and then have the ability to scale up quickly in order to deliver what’s needed.”
Woolhouse urges a policy of “perpetual standby” for a range of surveillance activities that provided useful data on covid. Although faster than most scientific projects, which can take years, COG-UK still required vital weeks to get going in 2020, he points out.
He adds, “The same was true of a range of other surveillance activities: the ONS infection survey, the CoMix behavioural survey, and the Zoe app—all created reactively to fill gaps in our response capability.”
In a health emergency every day counts. “Past investment in research was a predictor of readiness during the pandemic for genomics as with vaccine development,” said Peacock in a speech to the Association of Physicians of Great Britain and Ireland’s annual conference in Liverpool in April. Calling for a “national strategy for pathogen genomics,” she told the meeting that “future national funding should consider how to further develop sequencing innovations and expertise,” along with prioritising “interdisciplinarity, an important part of the scientific response to the pandemic in the UK.”
Peacock also called for support for academic departments to be able to contribute swiftly and effectively in an emergency. “Academic institutions are deep wells of expertise during times of crisis,” she told the meeting. “Given that the ability to mobilise is not straightforward, we need mechanisms that support the involvement of these institutions during emergencies.”
Genomic surveillance will play a bigger role in pandemic preparedness in parts of the world where infectious diseases remain a daily threat. Last month the Africa Centres for Disease Control and Prevention (Africa CDC) celebrated Africa’s “shift from being genomic data consumers to producers.” More than 120 000 SARS-CoV-2 genomic sequences have now been generated in Africa—a dramatic increase from the 5000 sequences in early 2020 when Africa CDC set up the public-private Africa Pathogen Genomics Initiative. This enabled sequencing of samples from African countries to be carried out in that continent rather than in Europe or the US, “where scientists would then claim intellectual properties on the data.”
Africa CDC had originally set out genomic sequencing plans in 2017, “when the continent was battling with Ebola, yellow fever, Lassa fever, and Rift Valley fever at a time when the pathogen genomics programme was only a dream awaiting actualisation,” said Yenew Kebede, head of laboratory systems and networks at Africa CDC, in April. The pandemic had been “an opportunity to strengthen [Africa CDC’s] systems, injecting urgency and momentum to empower public health institutions with genomic technologies.” It’s an initiative that the UK should perhaps now watch carefully.
Meera Chand, UKHSA deputy director, said in a statement, “Robust and effective genomic surveillance is vital to the global community’s ability to detect and respond to emerging pathogen threats and to ensuring that we are well placed to respond to future pandemics.
“UKHSA recognises the need to sustain genomics surveillance as an integral component of our mission to protect public health from current and future threats. We will continue to develop our domestic surveillance and to work with international partners, and we are committed to open data sharing to facilitate this."
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Competing interests: None declared.
Provenance and peer review: Commissioned, not externally peer reviewed.
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