A The new variant of SARS-CoV-2, the virus that causes COVID-19, is believed to be causing increased transmission of the disease in parts of the UK. The government has placed some regions, including London, under new, stricter coronavirus restrictions, known as Level 4. People in Level 4 zones will not be able to meet with anyone outside of their homes for Christmas, while those from the rest of the country will only be able to gather on Christmas Day itself.
Boris Johnson, the Prime Minister, and his senior scientific advisers said the new variant could increase COVID-19 transmission by 70% and increase R or reproduction number by 0.4.
What is the significance of this new discovery? The conversation asked Lucy van Dorp, a microbial genomics researcher and pathogen evolution expert, a few key questions about what we know at this point.
What do we know about this new variant?
The new UK variant, known as VUI – 202012/01 or line B.1.1.7, was first announced by Matt Hancock, the Secretary of Health on December 14. . Examining the SARS-CoV-2 databases, the first sample was taken from Kent County on September 20.
The variant carries 14 defining mutations, seven of which are in the spike protein, the protein that mediates entry of the virus into human cells. This is a relatively large number of changes compared to the many variations we have circulating around the world.
To date, the genetic profiles – or genomes – of this variant have been largely sequenced and shared from the UK, but include some in Denmark and two cases in Australia. A case has also been reported in the Netherlands. These countries all have very large genome sequencing efforts and it is very possible that these observations do not reflect the true distribution of this variant of the virus, which could exist without being detected elsewhere. We will know more as more genomes are generated and shared.
Thanks to efforts to share data, genomic surveillance and COVID-19 test results in the UK, it appears that this variant is now starting to dominate existing versions of the virus and could be responsible for an increasing proportion. of cases in some parts. across the country, especially in areas where the number of cases is increasing rapidly.
It is always very difficult to disentangle the causes and effects in these cases. For example, the increased occurrence of certain mutations may be due to viral lines carrying the increased frequency simply because they happen to be those present in an area of high transmission, for example due to human activities or the choice of interventions.
While this remains a possibility, there are enough observations regarding so far that this variant warrants very careful characterization, monitoring, and interventions to stem transmission.
Is it more dangerous?
Chris Whitty, the chief medical officer, made it clear that there was no evidence to date that this variant changes the severity of the disease, either in terms of mortality or the severity of COVID-19 cases for infected people. Work is underway to confirm this.
How do viral mutations occur?
Mutations are a natural part of the evolution of the virus. In the case of SARS-CoV-2, these mutations can arise due to random errors during virus replication, be induced by antiviral proteins in infected people, or through genetic mixing – known as recombination. . Although signs of recombination are currently not detected in SARS-CoV-2.
Most viral mutations are expected to have no impact. For example, when our team assessed individual mutation replacements in over 50,000 genomes from the first wave of the pandemic, we found none that significantly altered viral fitness – the virus’s ability to survive. and to reproduce.
However, every once in a while a mutation, or in this case a particular combination of mutations, can be lucky and give the virus a new advantage. Viruses carrying these combinations of mutations can then increase in frequency by natural selection in an appropriate epidemiological environment.
Where does the variant come from?
At this moment we do not know. To date, scientists have not identified any closely related viruses to support the theory that the variant was introduced from abroad. The observed mutation patterns are more favorable for a prolonged period of adaptive evolution most likely in the UK based on current data.
Mutation patterns similar to these have been observed in the course of SARS-CoV-2 in chronically infected patients with weaker immune systems. The current hypothesis is that such a scenario of chronic infection, in a single patient, may have played a role in the origin of this variant. This will continue to be studied.
How many variations of SARS-CoV-2 have we found?
There are several thousand strains of SARS-CoV-2 which differ on average only by a small number of determining mutations. It remains true that SARS-CoV-2 currently circulating worldwide has low genomic diversity. Subtleties in the mutations carried in different lineages can, however, be very useful in reconstructing patterns of inheritance.
As an example, work at the start of the pandemic used lineage assignments to identify at least a thousand SARS-CoV-2 introductions in the UK.
Why is this one different?
It is important to note that many mutations defining the British variant were seen in SARS-CoV-2 before and sometimes even quite early in the pandemic.
Yet the British variant, or lineage, is defined by an unusual number and combination of mutations. One of these mutations, N501Y, has already been shown to increase the binding of the virus to receptors in our cells. N501Y was first sequenced in a virus in Brazil in April 2020 and is currently associated with a variant of SARS-CoV-2 which is also increasing in frequency in South Africa – an independent line of B.1.1.7 which is also of concern.
The particular deletions identified in the spike protein of B.1.1.7 have appeared in several other lineages of the virus with increasing frequency and are also seen in chronic infections where they can impair antigenicity – recognition by immune antibodies. These deletions may also be associated with other mutations in the coronavirus spike protein binding region, including those seen in infections in farmed mink and a mutation that plays a role in the ability of the virus to escape the immune system in humans. B.1.1.7 also contains a truncated ORF8 gene, with deletions in this region previously associated with reduced disease severity.
The functional effect of these mutations and deletions, in particular when they are in the combination indicated in B.1.1.7, remains to be determined. The high number of mutations and the recent increase in the prevalence of this particular variant, as well as the biological relevance of some of the candidates for the mutation, underscore the need for further study.
What does this mean for the vaccine?
At the moment, we don’t know. While we should be reassured that the vaccines stimulate a broad antibody response to all of the spike protein, it is therefore expected that their effectiveness will not be significantly hampered by mutations. This is already tested.
However, there is growing evidence that other seasonal coronavirus species exhibit some ability to evade immunity over longer periods of time.
So it’s conceivable that we may reach a point where we’re forced to update our COVID-19 vaccines, like we do with influenza, to reflect the variants in circulation at the time. It’s too early to say if that will be the case now, but full genome sequencing, data sharing, and standardized variant reporting will be essential to inform these efforts.
Lucy van Dorp is a senior researcher in microbial genomics at University College London