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IIt was always predictable that the Sars-CoV-2 genome would mutate. After all, that’s what viruses and other microorganisms do. The Sars-CoV-2 genome accumulates around one or two mutations each month as it circulates. In fact, its rate of change is much lower than that of other viruses that we know of. For example, the seasonal flu mutates at such a rate that a new vaccine must be introduced every year.
Even so, over time the virus population will accumulate a few mutations in different combinations. The striking feature of the Sars-CoV-2 1.1.7 lineage that we discovered here at the Covid-19 Genomics UK Consortium (now familiar from the headlines as the ‘new variant’), is that its genome has a large number of mutations compared with other lines that we have collected in the UK. It has 23 in total, which sets it apart.
Most mutations are not of concern as they do not cause a change in any of the amino acids that generate the proteins from which the virus is made. When they do, it deserves special attention, especially when mutations (or deletions) occur in a region of the virus that could change the way it interacts with its human host. In particular, changes in the spike protein, which scallops the exterior of the virus and is the mechanism by which it attaches and enters the host cell, where it can replicate, are of great interest.
What worries scientists about the 1.1.7 line is that, alongside six mutations that don’t change any proteins, there are 17 (14 mutations and three deletions) that do. Preliminary genomic analysis of the 1.1.7 line shows that several of these mutations have already been described in other lines and have been shown to change the way the virus behaves. A mutation (called 501Y) has been shown to increase the strength of the protein’s binding to a receptor on the surface of human cells. A second change (69-70del) has been identified in viruses that have evolved to evade the natural immune response in some immunocompromised patients. But nothing can be assumed about the new variant and what these mutations mean. We need more scientific evidence to understand how this particular version of the virus behaves relative to others.
Here’s what we need to look for: if the variant spreads more easily between people, if it causes more (or less) serious illness, and if it can evade our body’s immune response. There is currently no evidence that lineage 1.1.7 causes more serious disease or escapes the immune system. There is also no reason to believe that the vaccines in deployment or in development will be less effective against it. But what seems more and more likely is that this lineage is more transmissible.
In the UK, the body reviewing new evidence regarding the virus is the Advisory Group on New and Emerging Respiratory Virus Threats (Nervtag). The last publicly available minutes show that Nervtag has “moderate confidence” that this new variant is significantly more transferable. The data examined included genomic analysis showing that this particular line was growing about 70% faster. Additionally, he found a correlation between a higher R value and the detection of the new variant in the test samples. (The R-value, remember, is the number of people each person transmits it to. The higher it is, the more it spreads.) They also noted that the variant has grown exponentially during a period when measurements national lockdowns were in place. It is still possible that there are other explanations for this rapid spread, but the idea that this variant is more transmissible is plausible and seems increasingly likely. Laboratory studies that are currently underway will answer this with certainty.
Concretely, this means that all our efforts to prevent the spread – by washing our hands, wearing masks and social distancing – become even more important. There is nothing to suggest that the new bloodline is somehow able to get around them, as long as we do them right.
One question that may never be answered is where the new variant came from. The first place we detected it, looking back through virus samples, was in Kent and London. But it’s not clear if this actually emerged there. It’s worth remembering that the UK is undertaking a lot more Sars-CoV-2 sequencing than many other countries, and the fact that we’ve found it here may say more about it than where it ultimately came from. Interestingly, it has been suggested that the variant may have appeared in an immunocompromised person who was chronically infected, with the virus being able to replicate and evolve in them over a long period of time. But, as always, more work is needed to figure out if this is really the case.
Looking to the future, we need to revisit our systems to predict if a given mutation could have health implications. In a recent investigation of mutations that our consortium performed, based on 126,219 genomes from positive samples, it was possible to identify 1,777 different amino acid modifying mutations in the spike protein gene.
Identifying mutations is an imperfect process. There are tools available that model changes in viral structure and function for a given mutation, but this modeling still needs to be confirmed by evidence. Not only that, but the large number of mutations that need to be modeled is vast. For now, the way we identify mutations that could be important to human health is by tracking the rate of the virus spread, carefully monitoring the severity of the disease, and putting systems in place to alert us when the virus was able to escape the immunity generated in the past. infection or vaccination. The new variant first appeared in early December when Public Health England was looking to determine why infection rates in Kent were not declining despite national restrictions, and we linked this observation to genomic data.
The story of the new variant shows how important genome sequencing is, but it highlights the fact that it’s only when this genomic data is linked to epidemiological and clinical information that it can make a difference in control. of disease. Fortunately, unlike past epidemics, we are able to use this tool quickly and on an unprecedented scale. We should be thankful for this, as it’s safe to assume it won’t be the last time it’s needed.
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