As the UK went into its first pandemic lockdown, back in March, the Government launched one of the world’s largest COVID-19 virus sequencing projects. Twenty million pounds was invested in the COVID-19 Genomics UK (COG-UK) consortium, to sequence as many SARS-CoV-2 viral genomes as possible, as fast as possible. How well this huge scientific endeavour would translate to real-world impact was at the time uncertain. Almost nine months, over 200 partners, and more than 131,000 virus genome sequences later, COG-UK presented its first showcase event demonstrating its major work areas.
So, what have been the main achievements so far?
How COVID-19 is transmitted into and across the UK
All viruses gradually accumulate changes to their genetic code. These genetic variants mostly make no difference to how the virus functions, but they are useful identification markers. Viruses can be grouped into ‘lineages’ based on the similarity of shared variants; in the UK there are currently around 3667 viral lineages identified.
Analysis of different lineages has shown that the pandemic in the UK was mostly initiated due to repeated introductions of the virus from travel to mainland Europe, followed by community transmission. After the first lockdown the number of different lineages was greatly reduced, but, as cases rose again a new set of virus lineages was identified. These lineages were again often associated with international travel, showing frequent virus importation. In Scotland and Wales it was also clear that there was significant importation of cases from England, whilst in Wales these lineages spread from East to West, consistent with their main travel links.
This knowledge can help governments make important virus control decisions, for example deciding when and where to close borders. Innovative ways to make results clearer are also being adopted. For example, in Wales lineage analysis results are fed live to the Welsh government with red, amber, green (RAG) ratings to allow easier communication of risk. It is important that communication channels between scientists and decision makers continue to improve, so that information produced by COG-UK and others can be acted on as fast as possible.
Local impact: hospitals, care homes and universities
At a local level, there are many examples of teams using genome sequencing to rapidly identify outbreaks. In Cambridge, sequencing allowed a cluster of hospital related infections to be identified, despite the patients being from two separate wards. Further investigations found the dialysis unit to be the common link between patients, allowing measures to be put in place to prevent any further outbreaks. Cambridge University Hospitals now carries out regular rapid sequencing of hospital acquired infections, with researchers working closely with hospital staff to communicate their results, informing which infection control measures to take. The COG-UK Hospital-Onset COVID-19 Infections Study (HOCI) study is currently evaluating the utility of using genome sequencing in hospitals across the UK.
Sequencing has been used in a similar way in care homes to understand if infections are being introduced from the wider community or circulating within care homes.
Regular sequencing of both symptomatic and asymptomatic students at the University of Cambridge has also taken place, to understand how the infections spread within the University and to what extent the virus spreads to the wider community.
Understanding how the virus is transmitted can help decision makers put appropriate control measure in place, and estimate the risk in different situations. Whilst ideally all care and educational facilities would perform targeted sequencing to understand their own situations, this may not be feasible on a national level. However, lessons from sequencing projects can still be applied to other institutions. For example, in the East of England sequencing showed that outbreaks across six different care homes were likely due to infected staff moving between the homes. This knowledge can be applied to all care homes, to ensure steps are taken to limit the spread of SARS-CoV-2 by staff, for example by performing regular testing.
Surveillance and mutation identification
Spreading rapidly across the UK is a new lineage of SARS-CoV-2 named B.1.1.7. The surveillance and data sharing efforts of COG-UK have facilitated the identification and monitoring of this lineage and others, as well as new virus variants. Surveillance is important to rapidly identify new variants that could result in increased disease severity, resistance to treatment and vaccination, or affect diagnostic tests. It must still be remembered that it takes time and research to identify the effects of new variants and viral lineages, something the COG-UK team and others are working on. Many variants rise to prominence simply due to chance, making it important not to jump to conclusions too quickly.
According to the latest information from Public Health England, evidence suggests that one variant of the new B.1.1.7 lineage (referred to as variant VUI-202012/01) transmits more easily, but there is no evidence that it is more likely to cause severe disease or mortality. However a B.1.1.7 variant has also been identified that meant a component of a PCR-based diagnostic test could no longer detect the virus. As the overall test used assessed several areas of the virus genome, in this case test results were not affected. However this finding clearly illustrates the need to use sequencing data to ensure diagnostic tests remain accurate in future, to avoid false negative results.
The Wellcome Sanger Institute along with other COG-UK partners have already developed a nationwide genomic surveillance system, and hope to continue to increase their speed and capacity to contribute to live detection and characterisation of new outbreaks. Once the population is vaccinated this will be especially important, to understand if the virus changes to escape the vaccination.
COG-UK has been an impressive achievement which is already demonstrating its worth. As well as setting up a UK wide sequencing project in record breaking time, there have been multiple examples of how scientific results can be translated into public health action.
There is always more to do, especially around improving data sharing, decreasing turnaround times, and understanding how best to balance the regulatory and delivery needs of a public health service alongside the more flexible environment required to continue to research and innovate.
Perhaps most importantly, COG-UK will define how we think about infection management and tracking going forward, allowing us to build on the infrastructure and protocols now established. As many, including the PHG Foundation, have been advocating for years, it appears the time has come to make genomics a cornerstone of infectious disease management in the UK.