Cambridge-led COG-UK consortium studying fast-spreading variant of Covid-19 virus to assess its impact
The Cambridge-led consortium carrying out genomic surveillance of the virus that causes Covid-19 has said studies need to be carried out “at pace” to confirm whether a new variant has any impact on the severity of the disease or effectiveness of vaccines.
There is currently no evidence to date that the variant, which is circulating fast in the South East of England, or any of the others studied so far, have such an impact, they stressed.
The Covid-19 Genomics UK (COG-UK) consortium, led by Professor Sharon Peacock of the University of Cambridge and involving public health bodies, academic partners and the Wellcome Sanger Institute at Hinxton, is sequencing about 10 per cent of the positive Covid-19 samples taken across the UK to study how the virus is developing.
The latest variant carries a set of mutations including an N501Y mutation in the receptor binding motif of the spike protein that the virus uses to bind to the human ACE2 receptor.
COG-UK reports: “Mutations arise naturally in the SARS-CoV-2 genome as the virus replicates and circulates in the human population. These accumulate at a rate of around one to two mutations per month in the global phylogeny.
“As a result of this on-going process, many thousands of mutations have already arisen in the SARS-CoV-2 genome since the virus emerged in 2019. As mutations continue to arise, novel combinations are increasingly observed.
“The vast majority of the mutations observed in SARS-CoV-2 have no apparent effect on the virus and only a very small minority are likely to be important and change the virus in any appreciable way.”
The greatest attention is being paid to mutations in the gene that encodes the virus’ spike protein, as this is associated with viral entry into cells.
COG-UK reports: “There are around 4,000 mutations in the spike protein gene at the present time. A small number of mutations are in a region referred to as the receptor binding motif (RBM) of the spike protein which is responsible for viral entry via its interaction with the receptor (hACE2) on host cells.”
The consortium adds: “There is a possibility that the roll-out of vaccination will lead to selection for mutations that allow the virus to escape from the effect of the vaccine.
“Public health agencies are central to the ongoing evaluation for this event and will require the effective and rapid detection of people who have had infection more than once, or else have vaccine failure, which could be explained by changes in the virus. Such cases will need to be prioritised to have their virus sequenced.”
The mutations in the new variant include the deletion of two amino acids from the spike protein, which could potentially make it spread more easily.
While this deletion has been spotted in several countries since the spring, it has been far more prevalent in the south of England since August and September.
It has been reported that the same deletion was spotted in samples from a Cambridge patient with a weakened immune system who was treated with blood plasma containing antibodies from a recovered patient.
The Covid-19 virus mutated during the treatment and it is possible that it became more resistant to the antibodies. The patient died from the Covid-19 infection.
Ravi Gupta, professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, told the Guardian: “We think there’s a mechanism for the virus to start escaping,” said “We need to crack down on it. We don’t know what it’s going to do long term but we can’t take a chance on it. It’s unlikely it’ll make people sicker, but it could make it harder to control.”
Prof Peacock had revealed that COG-UK, which was recently awarded a further £12.2million of government funding, aims to double its sequencing efforts in the new year.
She said: “The next few months will see us expanding our operations. Currently, we are sequencing around 8,000-10,000 SARS-CoV-2 genomes every week but aim to double this in the coming months.
“Strengthening our infrastructure will include further investment in our data repository powered and enabled through CLIMB, and the purchase of new equipment so that we can sequence more effectively. For example, we will invest in equipment at PHE (Public Health England) Colindale to support higher numbers of samples to be sequenced with a shorter turnaround time. We will also put more funding into staff since many members are volunteers, and this is not sustainable. Getting the leadership and governance right over time as we become increasingly delivery focused will also be of upmost importance.
“We also need to reduce the time it takes from the point at which a swab is taken to the moment that genomic data is available for that sample. Comparison of the sequences of two viruses can help to unravel whether a cluster of people with Covid-19 were linked (or not), but this will only be meaningful if completed within a timescale that influences infection control and public health interventions.
“We also want to increase our chances of early detection of mutations in the virus that could be important for human health, either because they may be associated with altered ability to cause, for example, more severe disease, or be less susceptible to vaccines. The sooner these can be detected and evaluated, the more prepared we will be.”
The consortium is spearheaded by the Wellcome Sanger Institute at Hinxton and the University of Cambridge, and also features NHS organisations, the four UK public health agencies and 11 other academic partners.
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