The legacy of COG-UK

Originally set up to drive research with the vision of developing surveillance capacity, COG-UK was never intended to be a long-term service for public health. For this reason, in April 2021, 13 months after leading the UK's genome sequencing effort for COVID-19, COG-UK began the process of handing over the routine sequencing of COVID-19 samples to a national sequencing service run by the four UK public health authorities. Taking place over several months, this transition was completed in August 2021 (COG-UK July 2021).

In many ways, the handover was a natural progression because routine SARS-CoV-2 sequencing is now seen as intrinsic to public health, which falls outside the remit of academics. Some of the rationale is explained by Ana Da Silva Filipe who witnessed the transition from Glasgow. She points out that 'academia is not a public health agency. It's not their role to continue to do public health work. They have research projects that they need to resume. So it did not make sense for academics to continue to provide what is now a service because we are meant to be doing research. On the other hand, from the public health agencies' point of view, they see it as a very important tool with diagnostic purposes and therefore it made sense for them to take on that role. So it got transformed into a service that is now run by public health agencies' (da Silva Filipe transcript).

Following the transition, COG-UK focused its energies primarily on research and is set to stand down completely at the end of March 2023 when its funding comes to an end. In its wake, COG-UK leaves an important legacy. Most notably, Professor Sharon Peacock who led the consortium from the beginning, says it provides a blueprint for 'how to sequence at scale in times of emergency' (Peacock, Galai). But, as can be seen from below, it also left a number of other important legacies.

Figure 16.1: The COG-UK logo.

Team science

Eighteen months into COG-UK's work, Peacock wrote that one of the key take-away lessons it provided was the importance of collaboration. She pointed out, 'The incredible impact of health research in supporting the response to the pandemic has not been achieved by one organisation or in siloes. It has been a genuine success story for "team science"' (Peacock July 2021). In December 2021 Peacock reiterated this view when she commented: 'The achievements of COG-UK were built on the hard work of our consortium members and partner organisations. For me, they are the unsung heroes of our work' (Peacock Dec 2021).

A similar view is expressed by Dr Catherine Ludden, COG-UK's operations director. She argues that one of COG-UK's biggest legacies was that it showed what could be achieved with everyone working together as a team (Ludden and Blane transcript). Dr Estée Török, who participated in COG-UK work from the University of Cambridge, also expressed the same view. For her, one of the 'fantastic things' about COG-UK was that 'it really brought together clinical and academic institutions, and public health institutions, in the UK, including in the devolved governments to really work together to set up genomic surveillance for a novel pathogen in real time (Török transcript). For Peacock, the fact that COG-UK managed to get 21 institutions on board and working together including all four public health agencies 'was a real triumph' (Peacock transcript).

Collaboration lay at the heart of COG-UK, from performing the sequencing through to data analysis. In this context, COG-UK acted as the glue to bring everyone together. Importantly, COG-UK provided the legal and ethical framework, a mechanism to distribute financial resources, and online tools. This supported the pooling of skills and knowledge, which was needed to respond to the national emergency caused by the pandemic. What also helped drive COG-UK forward was its culture and values. Peacock is very proud of the collegiate spirit that ran throughout the consortium from its beginning. She points out 'We shared everything and created methods that other people could use. There was no infighting in terms of “let me analyse my data and write up a nice paper before I release the data'" (Peacock transcript).

Just how effective the collaboration was is revealed by the number of genome sequences uploaded by the different COG-UK partners to the CLIMB database between 1 March 2020 and 1 August 2021, which can be viewed in detail in Appendix 8. Figure 16.2 highlights the pivotal role that COG-UK academic partners played in stepping up sequencing at a time when the capacity to do such work elsewhere was limited, especially in NHS laboratories.

Figure 16.2: Collective number of SARS-CoV-2 genomes published for each institution type are shown by the bars and the cumulative sums of these are plotted in black. Their final total publication numbers, as of August 2021, are displayed in the top left corner of each plot and the percentages of the COG-UK total that they account for are displayed in the top right corner. Credit: Daniel Power.

Figure 16.3 shows the cumulative sequencing efforts by each collective institution type between 1 March 2020 and 1 August 2021. Overall, the Sanger Institute led the way in terms of the number of genomes sequenced (64.7%), which reflects the capacity it had for carrying out high-throughput sequencing of the large volume of COVID-19 samples it received from the community testing sites run by the Lighthouse laboratories. Academic sites also sequenced a large number of samples (21.4%). Many of their samples were from patients who presented to local hospitals, although academic labs sometimes took Lighthouse lab samples when the Sanger Institute became overloaded. Public health agencies also did a substantial amount of sequencing (13.1%). The higher sequencing carried out in these places can in part be explained by the way COG-UK funding was distributed.

Figure 16.3: Area plots, stacked, showing the cumulative numbers of sequences published by the collective institution types, against time between 1 March 2020 and 1 August 2021. The black horizontal line shows the final number of sequences published by COG-UK on CLIMB. Credit: Daniel Power.

The number of genomes sequenced by NHS laboratories was relatively low, a reflection at least in part of the fact that at the start of the pandemic they were responding to high demand for diagnostic testing as their primary focus, and had less capacity to ramp up sequencing. Many people interviewed for this history who worked in NHS laboratories commented that sequencing for COVID-19 was a steep learning curve for them and in the long-run helped to extend their sequencing locally for other infectious diseases. While lower in number, the samples sequenced by NHS laboratories often provided important information which could, for example, be used to understand transmission pathways in hospitals.

Figure 16.4: Image used for COG-UK's Together Event.

Genomic surveillance for public health

Historically, COG-UK also provides an important lesson in how to structure genomic surveillance in a way that data can be collected and flow across all four nations of the UK. This was vital to getting an insight into the national context of the pandemic as well as what was happening at the local level to implement appropriate public health measures. Just how much of a milestone this was is highlighted by Dr Ewan Harrison, who worked alongside Peacock in the early days to draw up the Consortium Agreement. He points out that prior to the pandemic 'There had never been an agreement between all four UK public health agencies to share pathogen data. And not only to share it with each other, to then share it with the academic research community'. Both he and Peacock believe COG-UK helped set an important precedent in terms of how different partners can work together to systematically share genomic information across the four nations, which they hope will be retained going forward (Harrison and Jermy transcript; Peacock Dec 2021).

In addition to strengthening cooperation between different agencies, COG-UK demonstrated the value of embedding pathogen genomics capacity into the public health system at a national level. Before COG-UK, genomic sequencing was mainly undertaken in the UK by reference labs to detect and manage outbreaks of disease caused by food pathogens like Escherichia or Salmonella. But prior to COG-UK, the roll-out of a national genomic surveillance system had never been attempted, let alone in real-time. Just how novel COG-UK was as a concept is summed up by Dr Emma Hodcroft, a molecular epidemiologist who watched it unfold from Switzerland. She says 'Coming up with an unheard of sequencing programme that links together sequencing from across the UK and puts it in a database and organises all this metadata and makes that data available publicly, that was never a given. That was a wishlist' (Hodcroft transcript).

When COG-UK was first started many were unsure about what value it would bring to public health (Kwiatkowski transcript). As Dr Cordelia Langford, from the Sanger Institute, says, at that time there was 'an element of scepticism as to whether genomic surveillance was really worthy, or of use' (Langford transcript). Professor Emma Thomson who participated in COG-UK from Glasgow similarly remembers encountering some resistance to large scale genomics surveillance at Public Health Scotland. In part, this was because some people could not see what they would learn 'from genetic sequences' that they felt they could not 'get from shoe leather, epidemiological data, from looking at people's contacts and things like that.' But, she points out, their ability to conduct contract tracing was rapidly overwhelmed by the high number of cases which meant they could not 'keep up with everyone'. It soon became clear that genomics offered an important avenue for looking at transmission patterns and networks which was much more limited with the track and trace system (Thomson transcript).

The key turning point in attitudes came in December 2020 when the first variant of concern. Alpha, was found. Ludden argues that 'really opened everyone's eyes to genomics' because before that 'People didn't really buy into genomics as much' (Ludden and Blane transcript). Amy Gaskin at Public Health Wales also witnessed the same change. She believes that the identification of Alpha marked the moment 'when genomics came to the fore and the public policy people started to see why we've been doing what we're doing' (Gaskin transcript). Some idea of how much an appreciation for genomic surveillance grew is also highlighted by Peacock. As she says, 'the whole idea of pathogen sequencing is now part of our common language and common understanding. The public, policymakers and the government now all know about it. Before this people didn't have that understanding. It was very much seen as a test done in a distant lab that might be done for a foodborne outbreak or TB. What is new is that people are now saying sequencing is actually very valuable and it matters to me' (Peacock transcript).

Public attention towards COG-UK was first really switched on by the identification of Alpha. But its value goes well beyond the detection of new variants. Importantly, it has also proved how genomic data can be used to understand sources of outbreaks and transmission patterns, all of which are necessary for curbing the spread of infection at both the national and local level. Over the course of its history, COG-UK provided data on the introduction and transmission of COVID-19 in care homes, universities and hospitals and pinpointed how the disease spread through international travel (Peacock 2021). Behind the scenes, COG-UK data has also played an important role in efforts to improve the efficacy of vaccines and therapeutics (Marjanovic).

By demonstrating the use of genomic surveillance for COVID-19, the work undertaken by COG-UK has helped strengthen the case for extending its use to other pathogens that threaten public health. Indeed, many COG-UK participants argue that it has stimulated a stronger appetite for scaling up pathogen genomics sequencing capacity for public health (Marjanovic). As Peacock pointed out in April 2022, 'The potential of what we have built is vast, and we should continue to explore how it should be used to advance our understanding of pathogens, and how we respond to them to protect public health worldwide.' In the immediate future she believes that genomic surveillance will remain important to learning how to live with COVID-19, which she indicates can be supported by dialling up and down sequencing depending on each country's needs. Where she also sees it could be of immense value is 'in detecting known or emerging antimicrobial resistance' (Peacock, Galai).

The extent to which COG-UK has helped spread awareness of the value of genomic sequencing is captured in the interview with Dr Beatrix Kele, a clinical scientist at Barts Health NHS Trust. Contributing to COG-UK, Kele says 'opened up our eyes' to how much they could achieve with sequencing. According to her, she and her colleagues are no longer 'just thinking about COVID sequencing' and in the future, plan to use sequencing for outbreak investigations caused by pathogens like norovirus and influenza, as well as several bacteria resistant to antibiotics like MRSA (Methicillin-resistant Staphylococcus aureus) and Extended Spectrum Beta-Lactamase (Kele and Cutino transcript).

Some idea of how much COG-UK has helped shift perceptions of the value of genomics is also reflected in the interview with Dr Thusan de Silva at the University of Sheffield. He points out that the local genomic expertise built up through COG-UK helped persuade a local NHS Trust to set up sequencing in its diagnostic laboratory. He and his colleagues had been working towards establishing this into routine service for a decade (de Silva transcript). Dr David Studholme, a bioinformatician based at the University of Exeter, also indicates COG-UK's success helped catalyse and speed up the establishment of local pathogen genomic surveillance in the southwest region (Studholme transcript). The same thing has also happened in the case of the Public Health Laboratory in Bristol, which is now collaborating with the genetics department at the University of Bristol to set up sequencing locally (Muir transcript). According to Dr Sharon Glaysher, from Portsmouth Hospitals University NHS Trust's Research Laboratory, it also meant that sequencing technology is now seen by many within the NHS as 'more of a necessity than a luxury' (Glaysher transcript).

Expertise and equipment

COG-UK not only helped galvanise interest in genomic sequencing, but also helped expand expertise in the area. By February 2022, the consortium had helped to train over 800 staff across different professions and stages in career development to improve sequencing, analysis and interpretation skills. Many of those trained included clinicians, biomedical scientists, nurses, diagnostic laboratory scientists and technicians, as well as health-protection and infection control teams. By doing this, COG-UK leaves behind a trained workforce able to support the future roll-out of pathogen genomic sequencing for outbreak investigations and in the event of another pandemic (Marjanovic).

Figure 16.5: Photograph of scientists at the Sanger Institute sequencing samples. Credit: The Sanger Institute.

As well as nurturing a workforce, COG-UK invested in equipment and assisted in the development of protocols which helped bolster the sequencing capacity of several centres. In addition, COG-UK members and associates developed several software and visualisation tools for the rapid analysis and interpretation of large genome sequencing datasets. Together these tools have not only provided important information about the evolution of the virus, but also the immunological consequences of mutations, for example through COG-UK's Mutation Explorer dashboard.

Beyond training and equipment, COG-UK has also provided new ways of working which will be of benefit in the future. One of the clearest examples of where this has happened is at the Sanger Institute. Here, the expertise developed to scale up sequencing for COVID-19 samples is now being leveraged to further advance its malaria programme (Kwiatkowski transcript). It also laid the foundation for a new Respiratory Virus and Microbiome Initiative. Launched in January 2023, the new venture is being led by Dr Ewan Harrison who helped get COG-UK moving. According to Harrison the initiative grew 'out of the simple idea that what we've done for Covid, we should now be doing for all respiratory viruses, because if we can establish a better understanding of these viruses, we can be in a better place to understand their transmission and how to develop vaccines against them' (Geddes).

Personal impact

Many COG-UK participants felt a great sense of pride and privilege to have taken part in the effort. Some idea of the honour they felt is highlighted by Dr James Shepherd who participated from Glasgow. As he says, 'I was really lucky to be in the right place at the right time and to have the opportunity to contribute to it. I'm quite proud of it, it's certainly the hardest I've ever worked, but it's the best work I've done. And it felt like there was a group of hundreds of people all working very hard and producing something very useful' (Shepherd transcript). Tanya Brooklyn, who helped manage the COVID-19 sequencing at the Sanger Institute, also expressed the same sentiment. As she puts it, 'I wouldn't have missed it for the world' (Brooklyn transcript).

In many cases, COG-UK participants said it was a life-changing experience which they will treasure for the rest of their lives. On a personal level, many argue that COG-UK gave them scope to learn new skills and find a new career path. For example, Ludden comments, 'I've built personal skills that I think I will have for life. I've definitely grown as a leader. I've gone from thinking about a project and being in the lab and analysing data to now moving away from that, which I found quite scary at the beginning because I really loved being in the lab and analysing data, to actually just organising it. That was a big transition for me, but it's something I enjoyed, because I started to become more of a leader. Even though I was thrown into it, I realised it was something that I really enjoy and I now will progress my career as a leader rather than as an analyst' (Ludden and Blane transcript). In many cases, participants felt that COG-UK helped expanded their networks and enhanced their professional reputation (Török transcript; Meadows transcript, Robson and Beckett transcript; Miskelly transcript).

Figure 16.6: Cartoon of scientists working together. Credit: Open source image.

Overall, one of the lasting impressions of COG-UK is the great sense of achievement. Peacock says she is 'really proud that we did it at all. It would have been very easy not to step out and do it because it was quite a bold and risky step. It could have all gone very pear shaped and ended up with egg on our face with people saying we didn't need to waste all that money' (Peacock transcript). In Langford's case, she states the experience enabled her 'to find the confidence and words to express how privileged I am, and how proud I am, to work with so many people nationally, but also at the Sanger Institute, who have enabled and facilitated this incredible, this work that is contributing in such an important way' (Langford transcript).

Going Forward

With COG-UK set to stand down, discussions have started about how to go forward. The questions now being asked include how much SARS-CoV-2 sequencing needs to be done to detect a new variant, and how capabilities will remain viable and ready to respond in a coordinated way to the next pandemic. In terms of going forward with pathogen surveillance, Peacock believes COG-UK leaves behind ‘a mixed bag. It has certainly taken the lid off what sequencing can do and shown that it can make a difference to public health decisions. But right now, I think there's something of a hiatus in terms of thinking about what happens next after this pandemic.’ She believes that it will take a while for everyone 'to come out of the pandemic' and review where sequencing is most useful. This is already beginning to happen. For example, the Wellcome Trust recently set up a working group under the umbrella of the Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC) to review all the evidence on pathogen sequencing for antimicrobial resistance. Working together over six months the group are looking at where sequencing is being used and where the gaps are. Peacock is hopeful that this work will help 'relight the spark of interest in terms of sequencing in regional settings rather than simply centralised settings' (Peacock transcript).