As we learn more about COVID-19 disease and how the SARS-CoV-2 virus changes over time, the way we collect and sequence positive SARS-CoV-2 samples will continue to evolve. In this blog we take a look behind the scenes to find out more about our genome sequencing process.
The testing and sequencing of SARS-CoV-2 samples is playing a vital role in mapping how SARS-CoV-2 spreads and evolves. But what is happening behind the scenes? What is the journey of a positive test swab, and how likely is it that a swab will be genome sequenced?
What happens to my swab after I get tested for COVID-19?
Will my sample containing SARS-CoV-2 virus be genome sequenced?
Across the COVID-19 Genomics UK (COG-UK) Consortium, we strive to sequence as many SARS-CoV-2 viruses from people with COVID-19 as we can. But this depends on a variety of factors.
During times where the rates of COVID-19 infection are low (as we saw during the summer), it’s likely that over half of positive test samples collected nationally will be sequenced. But when cases increase (e.g. over 40,000 a week), the proportion of positive tests that we can sequence will be lower. We currently aim to sequence around 10,000 positive samples each week based on our present capacity, which we plan to increase in the coming months.
At sequencing labs across the COG-UK network, COVID-19 samples are received in individual tubes and in trays (known as plates) containing 96 ‘wells’, each containing a sample from a single swab. Every 96-well plate will contain a mixture of positive and negative samples, and our researchers must identify the wells corresponding to the positive tests to use for genome sequencing. This is known as cherry-picking, which can be time-intensive — and also limits how many genomes we can sequence. You can see here how the Sanger Institute has set up to do this at scale for the Lighthouse Labs samples.
With consortium partners continuously optimising and improving their operations, COG-UK aims to maximise the cherry-picking and sequencing capacity at which we operate.
How likely is it that someone with COVID-19 in my area will have their swab sequenced?
The map shows the cumulative coverage (the total number of viral genomes sequenced out of all COVID-19 cases since the start of the pandemic) up to the week commencing 2nd November 2020.
You can see more details in a report that can be downloaded here.
As a Consortium, we are working hard to find ways of increasing the number of genomes we sequence in areas with a higher concentration of people with COVID-19, the national hotspots.
We want to achieve equity of sequencing and good coverage across the UK.
Dr Catherine Ludden, who is Director of Operations at COG-UK, stresses that “To understand the evolution of SARS-CoV-2 and our ability to detect outbreaks, we must continue to sequence and analyse viral genomes from all across the UK.”
How can we improve our genome sequencing process?
As we learn more about COVID-19 and how the virus changes and evolves over time, the way we collect and sequence positive samples will continue to develop and adapt, to ensure the value of future analyses.
We need to be on the look-out for mutations that arise in the genome that could be associated with changes in the way that people respond to treatments and vaccines. Systems are being rapidly developed to track mutations of public health interest (that is, which could change the way that the virus behaves) as they arise in the virus population.
We need to minimise the time between someone being tested and the genome sequence of the virus from their positive sample being generated and available for analysis. The more efficient this process is, the faster we can learn from the insights the sequence data provides.
We have adapted our strategy to ensure that we capture samples from both NHS diagnostics labs (samples taken in hospitals, which are more likely to be of severe COVID-19 disease) and from the Lighthouse Labs network (more sampling of the general community and care homes). We are also now working to ensure we capture virus samples from imported cases — COVID-19 cases which have come from outside of the UK.
Dr Ewan Harrison, Director of Strategy and Transformation at COG-UK points out that “since the inception of COG-UK in April 2020, we have repeatedly revisited the best way to select samples for sequencing. It is a moving target, as we adapt to changes in the distribution of COVID-19 testing and respond to national priorities. This includes capture of SARS-CoV-2 samples from people in the Oxford (and in time other) vaccine trials”.
Ensuring we get this right is imperative to deliver the greatest benefit to everyone across the UK.
COVID-19 Genomics UK (COG-UK)
The current COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents a major threat to health. The COVID-19 Genomics UK (COG-UK) consortium has been created to deliver large-scale and rapid whole-genome virus sequencing to local NHS centres and the UK government.
Led by Professor Sharon Peacock of the University of Cambridge, COG-UK is made up of an innovative partnership of NHS organisations, the four Public Health Agencies of the UK, the Wellcome Sanger Institute and twelve academic partners providing sequencing and analysis capacity. A full list of collaborators can be found here: https://www.cogconsortium.uk/about/. Professor Peacock is also on a part-time secondment to PHE as Director of Science, where she focuses on the development of pathogen sequencing through COG-UK.
COG-UK was established in March 2020 supported by £20 million funding from the UK Department of Health and Social Care (DHSC), UK Research and Innovation (UKRI) and the Wellcome Sanger Institute, administered by UK Research and Innovation.
Icons credit: coronavirus symptoms by Berkah Icon from the Noun Project; testing by monkik from the Noun Project; laboratory by Phonlaphat Thongsriphong from the Noun Project. test tubes by Vectors Market from the Noun Project.