On May 14 May 2020, the World Health Organization warned that Covid-19 could remain a constant threat to public health, long after the pandemic stage. As the virus becomes an endemic infection – one that routinely circulates through populations – scientists are cognisant of the need to build better tools to monitor and track the contagion.
‘Genome sequencing’ is a critical part of this surveillance – a technique in which scientists sequence the DNA of SARS-CoV-2, the virus responsible for the current Covid-19 pandemic. As the virus can have slightly different genomes in different patients, it provides a way to map the spread of the virus, identify mutations and emerging new strains. When the number of cases in a certain areas rises and more viral genomes are sequenced, researchers can start to build a reference database, allowing them to see diff erent clusters of viruses spreading through communities.
The first genome sequence of Covid-19 was shared online on 11 January. As of 16 June, scientists from around the world had sequenced and shared 46,000 viral genomes through GISAID – a platform allowing rapid sharing of pandemic data, and an unprecedented scientific collaboration.
With many countries now having experienced the pandemic’s peak, or at least the first one, genomic sequencing offers a detailed picture of the virus’ spread, allowing countries to identify how the virus arrived on their shores and to visualise how the virus is spreading through communities, hospitals and care homes.
Capacity to analyse small genetic changes in the virus has ramped up, and has already yielded valuable insights. A £20 million-backed project called the Covid-19 Genomics UK consortium (COG-UK), is responsible for providing genome sequencing data to local NHS centres and the UK Government. Made up of NHS organisations, public health agencies, the Wellcome Sanger Institute, and 12 academic partners, COG-UK will provide information on whether or not outbreaks are due to introductions from other geographical regions, or through ongoing transmission within communities. This is vital when it comes to monitoring any ‘second wave’ that emerges.
Despite facing criticism for failing to scale-up testing, the UK is leading the charge on genome sequencing. COG-UK has 17 active sequencing centres and has analysed 29,000 SARS-CoV-2 genomes (as of 25 June 2020) – accounting for 53 per cent of the total number of genomes reported globally.
This research has revealed that the UK’s epidemic was seeded by imports of the virus from European countries, which peaked around 15 March: 34 per cent from Spain, 29 per cent from France, 14 per cent from Italy, and 23 per cent from other countries.
Hospitals and care homes would later become the ‘frontline’ of the UK’s epidemic. Between 13 March and 24 April, 299 viral genomes were collected from hospitalised patients across the east of England. Within 24 hours, sequencing data had identified that 66 cases had very closely related viral genomes, indicating recent infections. One cluster of the virus was suspected to have spread through a single ward, prompting a review of infection control and PPE measures in that hospital.
In Scotland, genomic sequencing has identified that 48 introductions of the virus from abroad led to outbreaks in local communities. Eleven days after the first detected case however, the bulk of new cases came from transmission of viruses already within Scotland – at a time before lockdown and social distancing measures were rolled-out on 23 March.
As well as tracking the spread of the virus through communities, COG-UK are hoping that their trove of genome data will guide public health intervention policies. ‘Due to our ability to track the genomes of the SARS-CoV-2 virus through sequencing by the COG-UK consortium, we can now link that with other forms of data to truly understand how the pandemic moves through a country or region,’ said Dr Ewan Harrison, fellow at the Wellcome Sanger Institute in a COG-UK statement. One of the aims of COG-UK's surveillance is to observe new mutations arising in the pool of SARS-CoV-2 viruses in circulation, and to identify whether any affect disease transmissability, or lead to particularly severe forms of disease. Although the impact on disease severity is still unknown, COG-UK identified on 25 June that SARS-CoV-2 viruses bearing the 'spike protein' 614D may have slightly different epidemic growth rates to other clusters in circulation.
COG-UK are now collaborating with Genomics England, biotechnology company Illumina and the NHS, to sequence the genomes of severely affected patients. Analysing data from both a patient’s genome and the virus’ genome will reveal how a person’s genetics influences their susceptibility to the virus, and if there are links between specific clusters of the virus and severity of illness. So far, it is unclear how a patient’s genetics may influence susceptibility, but there are already suspect genes. According to the immunologist Philip Murphy of the National Institute of Allergy and Infectious Diseases, variations in ACE2, a gene encoding a protein that the coronavirus uses to enter cells in patient’s airways, could make it easier for the virus to get into the patient’s cells.
At the start of a pandemic, it’s hard to perform these analyses because of the relatively low number of cases. But as cases build and more viral genomes are sequenced, it becomes possible to yield valuable information on how the virus spreads, and the types of treatment that might be effective.