My team at the Genomics UK consortium sequenced the new Sars-CoV-2 variant, but we’ll need more evidence to understand how it might change the pandemic
It was always predictable that the genome of Sars-CoV-2 would mutate. After all, that’s what viruses and other micro-organisms do. The Sars-CoV-2 genome accumulates around one or two mutations every month as it circulates. In fact, its rate of change is much lower than those of other viruses that we know about. For example, seasonal influenza mutates at such a rate that a new vaccine has to be introduced each year.
Even so, over time the virus population will accumulate a fair few mutations in different combinations. The striking feature of the Sars-CoV-2 lineage 1.1.7 that we discovered here at the Covid-19 Genomics UK Consortium (familiar now from headlines as the “new variant”), is that its genome has a large number of mutations compared with other lineages we’ve picked up in the UK. It has a total of 23, which is what sets it apart.
Most mutations aren’t concerning because they don’t result in a change in one of the amino acids that generate the proteins the virus is made from. When they do, that’s worthy of serious attention, especially when the mutations (or deletions) occur in a region of the virus that could change the way that it interacts with its human host. In particular, changes in the spike protein, which festoons the outside of the virus and is the mechanism by which it attaches to and enters the host cell, where it can replicate, are of great interest.
What’s concerning scientists about lineage 1.1.7 is that, alongside six mutations that don’t change any protein, there are 17 (14 mutations and three deletions) that do. A preliminary genomic analysis of lineage 1.1.7 shows that several of these mutations have been described before in other lineages, and have been found to change the way that the virus behaves. One mutation (termed 501Y) has been shown to increase how tightly the protein binds to a receptor on the surface of human cells. A second change (69-70del) has been identified in viruses that 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 in order to understand how this particular version of the virus behaves compared with others.
Here’s what we need to look out for: whether the variant transmits between people more readily, whether it causes more (or less) severe disease, and whether it can evade our bodies’ immune response. There is currently no evidence that lineage 1.1.7 causes more severe disease or that it evades the immune system. There is also no reason to think that the vaccines being rolled out or under development will be less effective against it. But what does look increasingly likely is that this lineage is more transmissible.
In the UK, the body that considers new evidence about the virus is the New and Emerging Respiratory Virus Threats Advisory Group (Nervtag). The latest publicly available minutes show Nervtag has “moderate confidence” that this new variant is substantially more transmissible. The data that it looked at included a genomic analysis showing that this particular lineage was growing around 70% faster. In addition, it found a correlation between a higher R value and the detection of the new variant in testing samples. (The R value, remember, is the number of people each person passes it to. The higher it is, the more widely it spreads.) They also noted that the variant grew exponentially during a period when national lockdown measures were in place. It’s 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 now being done will answer this for certain.
What this means in practical terms is that all our efforts to prevent spread – by washing hands, wearing masks and social distancing – become even more important. There’s nothing to suggest that the new lineage is somehow able to circumvent these, so long as we’re doing them properly.
One question that may never be answered is where the new variant came from. The first place we detected it, by looking back through virus samples, was in Kent and London. But it’s not clear whether it actually emerged there. It’s worth remembering that the UK undertakes much more Sars-CoV-2 sequencing than many other countries, and the fact that we’ve found it here may say more about that than about its ultimate origin. Interestingly, it has been suggested that the variant may have arisen in an immunocompromised person who was chronically infected, with the virus able to replicate and evolve in them over a long period of time. But, as ever, more work is required to understand if this is actually the case.
Looking to the future, we need to review our systems for predicting whether any given mutation could have health implications. In one recent survey of mutations that our consortium did, based on 126,219 genomes from positive samples, it was possible to identify 1,777 different amino-acid-changing mutations in the spike protein gene.
Identifying concerning mutations is an imperfect process. There are tools available that model the changes to viral structure and function for any given mutation, but this modelling always needs to be confirmed by evidence. Not only that, but, the sheer number of mutations that need to be modelled is vast. For now, the way we identify mutations that might be important for human health is by tracking the rate of virus spread, carefully monitoring severity of disease, and having systems in place to alert us when the virus has been able to evade immunity generated by past infection or vaccination. The new variant first came to light in early December when Public Health England was looking at why infection rates in Kent were not falling despite national restrictions, and we married this observation with the genome data.
The story of the new variant shows how important genome sequencing is, but it underlines the fact that it’s only when that genome data is linked to epidemiological and clinical information that it can make a difference in controlling the disease. Thankfully, unlike in past epidemics, we’re able to use this tool quickly and at an unprecedented scale. We should be grateful for that, because it is safe to assume that this won’t be the last time it’s needed.