Andrew Page, Dinesh Aggarwal and Sharon Peacock
The SARS-CoV-2 pandemic has hit the residents of care homes harder than any other part of the population, with many people across the UK and wider world losing their oldest and most vulnerable loved ones to COVID-19. We are looking to help safeguard our most at-risk individuals — and are searching for answers within genome sequencing data.
What can genome sequencing teach us?
Genome sequencing (or genomics) of positive SARS-CoV-2 viral samples allows us to understand how the virus moves between people and places during an outbreak. You can think of it as viral detective work. As the virus makes copies of itself, occasionally a random change happens that propagates, and it is through tracking these changes that we can build up a picture of how the virus spreads.
Using genomics, we can tell when two people have an identical, or very similar copy of the virus which we group into ‘lineages’, and we can see when people have different lineages. With genomics we can look at an outbreak in a single care home and get an idea of where the first infected person potentially came from. Knowing the source helps us to understand what we need to do better to prevent it happening again.
In a recent preprint, researchers from across the COVID-19 Genomics UK (COG-UK) Consortium have looked at all the studies worldwide which have used genome sequencing to better understand outbreaks in care homes. Only a small amount of work has been done on this area, with 11 studies in total from the UK, USA and The Netherlands.
So, what have we learned from genome sequencing in care homes?
- The majority of infections in care homes have not come from hospitals but from the local community
- As a result, when infections are high in a community you will find there are more care home outbreaks
- A high percentage of cases without symptoms (asymptomatic) is common
- Once the virus is established in care homes it tends to be of one dominant lineage (identical or nearly identical virus) found in both residents and staff
- Once the virus has entered a care home it spreads rapidly despite infection control measures
- To date there is no difference in the mortality rate between different lineages in care homes which have outbreaks. The mortality rates are high.
Through COG-UK, the UK has contributed to the majority of important studies on this topic. At the Quadram Institute, one of the 17 sequencing centres in COG-UK, we used genomics to show where the virus has spread between care homes. In the East of England, six care homes had the same distinct lineage of the virus, suggesting staff moving between the care homes may have led to the outbreaks. These linked outbreaks were found by looking for unusual patterns in the genome sequencing data for the region and could not realistically have been linked together by other means.
In another large-scale study, conducted by Cambridge University, researchers studied the SARS-CoV-2 genomes for 700 residents from 292 care homes. Through the use of genomic and temporal data, they were able to define 409 clusters of infection in the 292 homes. This highlighted outbreaks among care home residents and independent introductions with limited onward transmission were the two main patterns of spread observed. Finally, colleagues in PHE, were able to use genomic data to link resident infections to staff, but highlighted how both genomics and routine epidemiology need to work together to most reliably identify likely direction of transmission.
We don’t believe every sample needs to be genome sequenced in a care home outbreak. Once a few positive samples are sequenced, it is enough to get a reasonable picture about what is circulating. It is more important to take a wide selection of samples from those who test positive, and randomly choose a few on an ongoing basis and genome sequence those, so you can get a picture of the pandemic in real-time.
Interestingly, one US study in Washington state took all residents’ genomes in an outbreak, and if they were 100 per cent identical, gave them the same letter, then took a map of the care home residents’ bedrooms and overlaid the corresponding letters. This clearly showed that residents whose bedrooms were beside each other were more likely to be infected with a 100 per cent identical virus.
How can we protect our most vulnerable?
Given that through genomics we now have a much more developed knowledge of the virus in relation to care homes, what do we need to change to better protect our most vulnerable? The COG-UK Consortium recommendations to the UK Scientific Advisory Group for Emergencies (SAGE) include:
- Taking steps to limit the spread of SARS-CoV-2 to care homes from the community, staff, healthcare workers and hospitals
- Treating all care home staff (not just staff with direct contact with residents) as one group subject to the same infection control measures
- Residents whose rooms are located near the bedroom of a resident who is positive should be considered as very high risk
- Continuing the use of genomics in a targeted way in care homes to help identify, track and control the virus
- For the science community, genomic and epidemiological data with sufficient metadata (additional information that enables more in depth genomic analysis) should be released to public archives.
Finally, a vital aspect of undertaking genome sequencing is rapidly and openly sharing the results and underlying data with others. The scientific community in general still have work to do on this front, with many studies not making their data openly available, or public archives not allowing data to be openly available.
This virus is on track to be the most widely sequenced organism in history. We need to ensure that people from all over the world can understand and interpret the data, so that every country can utilize it to help combat the COVID-19 pandemic.
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/
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. For more information, visit: https://www.cogconsortium.uk.
COG-UK was backed by the Department for Health and Social Care Testing Innovation Fund with an additional £12.2M funding boost on the 16th November 2020, which will facilitate the genome sequencing capacity needed to meet the increasing numbers of COVID-19 cases expected in the UK this winter.