By Professor Sharon Peacock
Launched in the spring of 2020 as part of the UK response to the emerging pandemic, the COVID-19 Genomics UK (COG-UK) consortium has been on an extraordinary journey over the last three years. The work of standing up a national SARS-CoV-2 genomic surveillance programme from scratch in a matter of days has been likened, by myself and others, to assembling an aeroplane from its component parts while already in the process of taking off. Despite some precarious moments, and at times being held together by little more than hard work and an unlimited supply of good will, the consortium did get off the ground. And it flew magnificently, despite the turbulence all around.
Much as an aeroplane may be employed for different functions over the course of its years in service, COG-UK has undergone several refits over time, showing agility, flexibility, and a fluid strategic focus as it pivoted from being a large-scale distributed sequencing and data analysis effort to a consortium that increasingly facilitated pandemic-relevant genomics research and training. Now, having served its purpose in responding to the threat from SARS-CoV-2 and helping to create a template around which lasting systems for pathogen genomic surveillance can be based, it is finally time to retire COG-UK.
At the end of their service life, many aeroplanes end up in decommissioning facilities, picked over for parts, and then parked in desert graveyards until scrapped. However, it is my hope that COG-UK will be judged as deserving of a place in the pandemic response equivalent of an aviation museum, to be admired, studied, and learned from for decades to come.
Back to the start
When the earliest UK cases of COVID-19 were being recorded, a flurry of discussions, followed by a meeting held at the Wellcome Trust building, resulted in the drafting of a proposal for the rapid development of a national capability for SARS-CoV-2 sequencing to inform public health responses (see the History of COG-UK). The vision for SARS-CoV-2 genome sequencing needing to be an integrated consortium effort grew out of recognition that while daily sequencing capacity in the UK NHS and public health agencies was limited, the UK benefited from world-leading facilities and expertise in pathogen genomics and bioinformatics present across its combined public health agencies, universities, and research institutions.
The goal for this consortium was to be “the generation of actionable data which, when combined with epidemiological and clinical information, has the potential to inform interventions and policy decisions during the current UK COVID-19 epidemic”. Specifically, the envisaged consortium would generate a genomic dataset that could be integrated with epidemiological data and patient health records to allow: i) real-time monitoring of introductions, community transmission and outbreaks; ii) assessment of changes in transmissibility and virulence; and iii) evaluation of the impact of treatments and non-pharmaceutical interventions. In addition, undertaking advanced research that integrated human genomic and health data to understand the biology of SARS-CoV-2 and its impact on those infected, as well as building capacity for future pandemic preparedness, were identified as important deliverables.
While noting the risk of being seen as marking my own homework, I firmly believe that COG-UK members not only met, but substantially surpassed all expectations over the course of the past three years. Together, COG-UK members used what was, by the scale of many other aspects of national and international pandemic responses, a relatively modest amount of funding, to deliver a range of outputs that impacted the course of the pandemic to date and will continue to influence the adoption of genomic technologies for disease surveillance for generations to come. Indeed, you do not need to take just my word for it – this view is validated by the independent evaluation undertaken by RAND Europe of how COG-UK delivered against its objectives, which concluded that “COG-UK made a significant and valuable contribution to the UK’s public health genomics landscape”.
Leaving a legacy
In terms of return on investment for the £32.2M awarded to COG-UK over the course of the pandemic, the bulk of the funding went into sequencing what was at the time an unprecedented number of viral genomes, generating a SARS-CoV-2 dataset containing ~ 1 million genomes by the end of 2021 (when the consortium handed over responsibility for routine sequencing to the four UK Public Health Agencies). This dataset, together with the ~2 million additional genomes sequenced subsequently in the UK, has been used by public health workers and scientists to analyse and understand COVID-19, and has fed into more than 100 publications by COG-UK members over the course of the last three years. Importantly, as the SARS-CoV-2 genomes sequenced in the UK can be linked with epidemiological, clinical, and human genetic data, the resulting rich dataset will provide an invaluable resource for scientists studying COVID-19 for decades to come.
While important, the dataset is only part of the picture. No one had undertaken genomic surveillance on anything like this scale previously, which necessitated the development of data management and analysis systems, scaling up of sequencing facilities, and an expansion of the existing genomics and bioinformatics skills and knowledge base. As with the data generated, the learning and expertise gained through this process will benefit the field, and the application of genomics in public health, for future generations. In recognition of this, we obtained additional funding from the Wellcome Trust and the Foreign, Commonwealth & Development Office to establish COG-Train, an international education initiative to provide open access learning in SARS-CoV-2 genomics, and in the application of genomics to understand and control infectious diseases more broadly. Led jointly by COG-UK and Wellcome Connecting Science, this hugely successful programme has worked with international researchers and public health experts to deliver free online training to thousands of learners in more than 100 countries worldwide, further magnifying the consortium’s impact at a global scale.
As the emergency gradually receded, and as sequencing responsibilities were transitioned to the public health agencies towards the end of 2021, COG-UK moved to helping to prepare for future emergencies by refocussing on research, data linkage and training. The residual money from the original grant went further than expected because of innovations in sequencing methodologies, which led to an almost halving of the cost per sequence generated over the lifetime of the consortium. Ever conscious that this was tax-payers money and conscious of the responsibility to spend each pound wisely and to good effect, remaining funds were used to provide seed funding for 17 research projects that would provide new insights to control this pandemic, and to prepare for the next. These focussed on: i) monitoring and understanding the emergence of SARS-CoV-2 variants with the potential to transmit more readily and/or circumvent immunity; ii) integrating pathogen genome sequencing data with diagnostic and rapid genotyping data to strengthen pandemic preparedness; iii) developing online resources to improve access to stringent quality control processes for SARS-CoV-2 genome data; iv) improving linkage and integration of genomic data with different types of epidemiological and clinical metadata; and v) developing metagenomic technologies for the surveillance of known and unknown pathogens with the potential to impact human health. We also funded a seed funding scheme to support seven early career scientists to kick start research projects that had been delayed while they devoted their time to responding to the pandemic. Collectively, the outcomes of this research will feed into our understanding of SARS-CoV-2 and our ability to identify and respond to future pandemic threats and will continue to amplify the legacy of COG-UK in the years to come.
Finally, consistent with the collaborative and open approach that brought together a wide range of partner institutions and members, COG-UK has run a series of events through which to share our scientific advances and provide forums for discussion. These have included seminars and science showcases, where consortium members have shared their analyses and insights with each other, and with the wider public. Also included is the Women in COG interview series, which showcased the lives and work of inspirational women (and some male supporters and allies) from across the COG-UK network and from outside of the consortium, and which was recently distilled into a book (Snapshots of Women in COG: Scientific Excellence during the COVID-19 pandemic). Everything we have achieved will be gathered in the ‘History of COG’ exhibition, which is currently being developed. The online exhibition will create a lasting record of not only the consortium achievements, but also the retelling of the human story from the perspective of more than 80 consortium members.
Out of adversity
When called upon, more than 600 people stepped forward to join COG-UK and work to realise the public health benefits of large-scale genomic surveillance in tackling the COVID-19 pandemic. While large sections of the population moved to working from home, many consortium members found themselves working in near deserted laboratories, maintaining social distancing from colleagues while going about the tasks needed to prepare samples and sequence SARS-CoV-2 genomes. Most had to drop or postpone other projects as they volunteered their time to the consortium, often working incredibly long hours and sacrificing time with family and friends, despite the unsettling times and the terrible toll being placed upon society by SARS-CoV-2. As with the wider communities in which we live, so have consortium members also been impacted by COVID-19, either personally or through the impact on loved ones.
However, out of the adversity imposed by this global crisis, success has also been born. While the pandemic might have been expected to leave a lasting scar on the lives and careers of consortium members forced to change their plans and focus on tackling the emerging crisis, there are many instances in which people who rose to the challenge have turned the adverse circumstances into opportunities. Rather than seeing their career progression stunted by the pandemic, many consortium members developed new skill sets and have since built on their experience with positive steps forward, often in areas that might not otherwise have occurred to them. We have seen members move from studying for a PhD in the most difficult of circumstances to take up post-doctoral positions at internationally renowned universities. We have seen members move to become independent scientists, running their own research groups for the first time. We have also seen members move from academic research positions into industry, or into science policy and communications to continue their career outside of the laboratory.
Across the consortium, people found strength and determination in the worst of times and have gained skills and experiences that will prove highly valuable as they move through their working life. I am not surprised that their fortitude is being recognised with new career opportunities, and through local, national, and international awards. I am intensely proud of the often-heroic efforts of members from across the consortium and consider the positive impact on their lives and careers to be among the most important outcomes of COG-UK.
Considering the limited examples prior to the pandemic of pathogen genomic surveillance in near real-time or at a scale sufficient to impact public health outcomes, one of the major lessons that I take from COG-UK is not that we helped to lay down the details of how to achieve large-scale genome sequencing but that it can be achieved. Policy makers and public health experts are no longer sceptical of the value that genomic insights can provide, and increasingly recognise the importance of developing the genomics infrastructure and knowledge base, and making this a central part of efforts to tackle a range of areas relevant to human health and the environment.
Beyond this, COG-UK blazed a trail in showing how through teamwork and coordination between academia, public health, clinicians, and industry, we can rapidly establish networks that provide infrastructure to the country during times of emergency. Even now, when responsibility for routine sequencing has moved to the public health agencies, I am certain that if the worst were to happen and we needed to rapidly expand sequencing to counter a new pandemic threat, academia would step forward once again. Ensuring that we maintain a sufficient cohort of scientists trained in using genomics and bioinformatics would provide a greater degree of resilience. While we cannot realistically expect that public health agencies will have funding to maintain excess sequencing capacity and personnel just in case, having a larger pool of researchers who use genomics to address their scientific questions (whether in human genetics, microbial genomics or antimicrobial resistance), could provide surge capacity to be called upon if needed. This approach is more than an insurance policy, spending on a device only to be used during an emergency, but rather would be investing in something that has multiple potential uses in day-to-day scientific life but that can be rapidly repurposed in times of need. Such considerations should clearly be baked into decisions about what research and infrastructure to fund in the future.
So. Farewell then COG-UK
After three of the most eventful years most of us are likely to experience, and what represents a substantial proportion of our working lives if not in years, then in content, it is finally time to say farewell to COG-UK. I believe that the collective efforts and outputs of all consortium members have helped to leave an indelible mark on the progression of genomics from being a tool used mainly for research, to becoming far more integrated into day-to-day clinical and public health practices. This is the part of our legacy of which I am particularly proud. To all COG-UK members, their family and friends who helped to carry the burden, our supporters at all partner institutions and funders, I recognise and appreciate all the time and energy that you put into making COG-UK the success that it has been over the past three years. It has been an honour and a privilege to serve as executive director and chair for COG-UK, and working with you all has been the highlight of my career. I wish you all the greatest of success in carrying forward and building on what we have achieved together.
For a full list of all the partners and individual members of the consortium click here.