Commentary: COG-UK report 12 – 15th October 2020

Commentary for report 12 – 15th October 2020

As of 22nd October, the COVID-19 Genomics UK (COG-UK) Consortium has sequenced more than 81,000 SARS-CoV-2 virus genomes from the UK, representing about 45 per cent of the global total.

Report 12 presents details of three separate studies using the genome data, and a summary of nationwide outbreak investigations that have used COG-UK genome data.

The information shows the ongoing state of the research, and has not been peer-reviewed. Conclusions may change as more evidence becomes available.

The first study is into a genetic mutation of the virus, termed N439K. This mutation results in a change to the Spike protein of the virus – the protein it uses to enter human cells. Because of its location, this mutation could affect a person’s immune response to the virus. The report stresses the need for systematic monitoring of virus mutations, especially when vaccinations begin.

The second study details the use of viral genomic data in Norfolk, where the data has enabled local outbreak management. The third study assessed respiratory disease in cats, associated with human-to-cat transmission of SARS-CoV-2. Finally, there is a summary showing COG-UK data and tools have been used in over 120 SARS-CoV-2 outbreak investigations in the UK.

N439K Mutation

Researchers around the world have been monitoring genetic changes in the virus, which accumulate as it replicates and transmits. The aim is to understand if any changes, or mutations, have an effect on the virus’s function, the severity of disease it causes, or transmission. So far, no mutation seen has altered the disease severity that the virus causes.

There is a focus on changes that affect the virus’s characteristic Spike protein. Like all coronaviruses, the SARS-CoV-2 virus has proteins that stick out of its core. These Spike proteins are the ‘crowns’ that give coronaviruses their name. It is this protein that allows the virus to attach to, and then enter, human cells. Any mutations that affect the Spike protein are vital to monitor, as they could potentially affect its function. It is also a part of the virus that our immune systems can ‘see’ and respond to. It was reported previously that a mutation in the Spike protein called D614G has increased in circulating viruses, in a way that is consistent with a slight increase in the rate of transmission.

COG-UK researchers, led by Professor David Robertson and Professor Emma Thomson at the University of Glasgow, assessed all mutations in the Spike protein. One of these – N439K – was of particular interest. N439K results in a change to the part of the Spike protein that binds to human cells. It is stable in the current virus population; it was seen in over 500 samples in Scotland early on in the UK epidemic, but then died out following the lockdown in March. It is now present again in virus samples from across Europe, the UK and the US. The wide spread of this mutation indicates the virus can thrive with such mutations – there is no detriment to its function.

Once vaccinations begin at scale, the Spike protein will be under ‘selective pressure’, as many vaccines are targeted against it. It is possible that viruses with certain mutations will fare better under a vaccine-primed immune response than others. Ongoing, early-stage, laboratory studies support this hypothesis. Work has shown that virus with the N439K mutation is able to resist monoclonal antibodies – like those being trialled as treatments – yet still bind to its target on human cells. But unlike a monoclonal antibody treatment, vaccines will prompt the immune system to make a range of antibodies, and so even if the Spike protein can resist one, it is likely another will be able to neutralise the virus.

The researchers stress the importance of systematically monitoring Spike protein mutations, finding and assessing new ones to understand their effects. This will be essential in the run up to any vaccine being introduced. The COG-UK team has set up a group, and systems, with the dedicated aim of monitoring new and existing mutations, prioritising those that need in-depth analyses.

Local Outbreak Management

Researchers led by Dr Andrew Page at the Quadram Institute in Norwich, report on the analysis of 1,035 SARS-CoV-2 genomes collected in Norfolk between March and August 2020.

They combined genome sequence data with clinical data to understand the origin, genetic variation, transmission and spread of SARS-CoV-2 in the region. They confirmed an outbreak at a food-processing facility and ruled out a hospital setting as the source of another outbreak. Long term follow up found no evidence of reinfection.

The team also found 16 viral variants, or lineages, in health care workers that were not present in patients, showing that PPE and infection control measures work to stop transmission of the virus.

For full details, view the study on MedRxiv.

Human to cat transmission

Professor Margaret Hosie at the University of Glasgow and colleagues looked at transmission of SARS-CoV-2 between humans and cats. Two cats from different COVID-19 infected households in the UK were shown to be infected with SARS-CoV-2 from humans.

There is no evidence of cat-to-human transmission, or that any domestic animals play a role in the epidemiology of human infections with SARS-CoV-2.

For full details, view the study on BioRxiv.

Summary of studies using COG-UK genomic data

COG-UK data and tools have been used in more than 120 live and retrospective SARS-CoV-2 outbreak investigations. This includes outbreaks in hospitals, communities, workplaces and settings managed by local authorities. For examples, see ‘COG-UK genomic surveillance in action’.

As the speed and scale of SARS-CoV-2 genome sequencing increases, the ability to use genomic data to investigate a wide range of scientific and public health questions is also growing. COG-UK aims to provide a large scale genomic surveillance service to support the investigation of more live outbreaks in the UK.