Tier 4, mutant new-strain COVID

I’d been hoping to finish this blog with a final post about vaccines, but I’ve been asked enough times about the new coronavirus variant in the South East of England over the last few days to see that a lot of people are worried about this. So I will do my best to explain what this is, and what it means for us and the vaccines, from my point of view (10 min read).

Take home message (TL;DR): Is this serious? Yes, unfortunately I think so. Do we need to panic? No, absolutely not. This mutant is not part of a cover-up or excuse I’m afraid, it is a real threat and warranted the response it has received. There is still hope for effective vaccines BUT we absolutely have to be sticking to the rules now more than ever.

This post is a bit more in-depth on the biology than usual, so time to dust off your knowledge of viruses, and let’s do this…

Quick disclaimer to start: I’ve spent 15+ years studying/working at the interface of chemistry and biology – I’m not an expert immunologist/virologist/epidemiologist – but I do have a broad understanding of science and I know the experts to listen to. I’ll try to explain what just happened as best I can, and apologies in advance to those experts whose scientific field I am about to trample on. N.B. I don’t own shares in any pharma companies, I’m not funded by the Gates Foundation, I really don’t like the UK government, and I don’t want to control people… I’m just doing this in my spare time to try to help worried friends/family – and believe me, if you’re sick of hearing about coronavirus, I am definitely sick of spending my evenings/weekends writing about it...

What are mutants?

I guess most people will have seen/read/know something about the structure of viruses: they’re basically an envelope made up of fatty molecules, with various proteins that are the bits that actually do things, and inside is the genetic information (the RNA code) that describes how to make each of the proteins. We could “basically” therefore describe a virus as ‘a set of genetic instructions for how to make a virus‘ – once the instructions are inside a host cell, it makes more virus, which infects more cells, and that means more instructions to make more virus, and so on, and so on…

However, when these instructions are repeatedly being made over and over again, sometimes there will be an error introduced (almost like a typo) which results in a small change in the genetic code. The term ‘mutant’ may sound quite scary, but that’s actually what a mutation is here – it’s the typo in the genetic code – and results in a new ‘variant’ of the virus. These mutations happen at random all the time with viruses – some viruses are very sloppy at reproducing their genetic codes (e.g. HIV) – SARS-CoV-2 happens to be relatively good, and is estimated to only pick up about 1-2 mutations per month. This change in the genetic code will in turn change the structure of proteins that are made from the instructions in the genetic code (remember these proteins are the bits that actually do stuff). Often these changes will result in a less effective virus and the mutant will die out. Sometimes the changes don’t make any difference to the virus. Other times, however, the change will result in a more infectious virus, and then that mutant will spread more (the evolutionary selection that leads to ‘survival of the fittest’).

This appears to be what happened in the South of England; SARS-CoV-2 picked up random changes in the genetic sequence that has made it more infectious (more on this in a second). Note that this doesn’t appear to have made the virus more deadly, because actually being less deadly would be an evolutionary advantage as it would give the virus more of a chance to spread. So this may leave people wondering why all the fuss if COVID-19 still only kills 0.5% of infected people?

So… to say this as clearly as I can because I have found this is the most important & overlooked fact in the pandemic:

The fatality rate from COVID-19 is going to be higher when the healthcare system is overrun as people will be refused treatment.

Grasping that fact will explain much of the global Coronavirus response, and why every country on earth has chosen to fight this (e.g. lockdown-light Sweden’s recent masks/gathering restrictions/work from home orders when their health service reached capacity, countries building entire hospitals in weeks, etc.). See more details in this post. Without grasping this fact, I’m afraid that the Coronavirus response will probably seem like an overreaction and that sadly leads to a slippery slope of conspiracy theories as the only explanation… I’m sorry but I’ve not been able to find a way to help people back if they choose to go down this path.

What’s the big deal about this mutant?

The threat of this new SARS-CoV-2 variant lies in spreading quicker: more people getting sick in one go means a more overrun heath service, and that means even more excess deaths. We’re not talking near 0.5%, otherwise the global response wouldn’t have been what it is. Luckily for us the UK government didn’t listen to the lockdown skeptics saying that we should let the overflow Nightingale Hospitals fill up before introducing any restrictions – because where would that have left us right now with our more infectious variant?.. Well done, government (for once). Also luckily for us, for all the slagging off that PCR tests get, which I genuinely don’t understand (and that’s not an invite for people who have never run a PCR/don’t know the difference between a PCR and a multiplex RT-qPCR/have never set up a screening assay, to try to explain it to me), we still do these tests. Again, well done government. The PCR tests look for 3 genetic sequences to identify SARS-CoV-2, and as it happens one of these genetic sequences was one of the mutated ones – this means by loss of this one genetic sequence we could see the spread of the new mutant compared to the original SARS-CoV-2 (data below).

(Top) University of Birmingham Turnkey lab data showing increasing % of the mutant in positive tests from early December.
(Bottom) Milton Keynes Lighthouse Lab data showing increasing spread of the mutant (orange) from late November.

New variants are occurring all the time, we have already seen many across Europe during the pandemic and I think about 4,000 mutations have been identified so far. Mutants can often become dominant through chance just by happening to find a susceptible population at the right time rather than actually being more infectious. However, the fact that this mutant rapidly overtook the original SARS-CoV-2 (becoming responsible for ~70% of positive tests in just 2 weeks in the data above) is the reason for concern – especially as this happened during “Tier 3” restrictions, meaning these restrictions weren’t containing the new variant. Hence the urgent switch to Tier 4, which was another painful U-turn but absolutely had to be made. Again, well done government. It’d be naive to think this mutant is an English problem – if the mutant is better at spreading, evolution means similar mutants will likely occur elsewhere, and will become the dominant variant when they do. Identifying the mutant now is actually a result of the high level of genetic sequence monitoring performed in the UK – I have seen multiple experts cite the UK as leading the world in this analysis (partly, well done government – not going to give them all the credit). Similar mutations are likely occurring across the world, we probably just we don’t know about them. Likewise, this variant is probably already in other areas/countries, but just hasn’t been detected yet – travel restrictions on the UK may be a sensible response for other countries, but it may already be too late to avoid the need for the equivalent “Tier 4” restrictions elsewhere if this variant has taken root.

So what is this particular variant?

There are actually 17 changes (mutations or missing parts) in this particular SARS-CoV-2 variant, with many located in genetic instructions that describe how to make the Spike protein. The Spike protein is the part of the virus that, as we probably all know now, allows SARS-CoV-2 to attach to human cells (by sticking to the ACE2 receptor). Here is what part of the Spike protein stuck to part of ACE2 looks like:

This is determined by a technique called Xray crystallography (one of the fantastic things we can do with a particle accelerator). These structures are freely available here if you want to have a look them in 3D. Citation Lan et al, Nature (2020)

What this may look like is two squiggley lines next to each other… and that is exactly the point I want to get across. A protein is actually a very long, linear string of building blocks (called amino acids) that folds into a particular shape – a change in the genetic code for how to make the protein doesn’t necessarily change the entire protein, it may only change a single building block within that string. In the case of the new SARS-CoV-2 Spike protein, we see 9 changes in the building blocks – but that is 9 changes out of a total of ~1,200 building blocks.

It’s currently not entirely clear why these changes have lead to a more infectious variant. The changes may make attachment to human cells more efficient (some of these mutations were already believed to do this) or the changes may affect the amount of virus that is produced during an infection (the viral load) – or maybe both – I’ve not seen any conclusive data/arguments either way on this yet, but I’m sure people will be working hard to answer this. An alternative is that the changes allow the virus to evade the immune system. As you may also be aware, the vast majority of vaccines in development target the Spike protein, so you may be wondering why aren’t scientists freaking out about the vaccines now…

What does this mean for vaccines?

Whilst the thought of a virus evolving as we fight it may certainly seem daunting, I should probably point out again that you are also the product of millions upon millions of years of evolution – if you want to see quite how remarkable evolution made you, just try googling why your fingers go wrinkly in the bath

The immune system is one of the best examples of how remarkable evolution is, and this is a topic that is vastly more complex than I will be able to do justice to in this description… but I will do my best to explain why a vaccine that trains the immune system to fight this virus may still help against mutant variants (immunologists please forgive me).

One part of our immune defense is antibodies produced by B-cells, these antibodies can bind to the Spike protein and block it from sticking to the ACE2 protein thus preventing the virus invading cells. Antibodies can also recruit macrophages, which are cells that can engulf and destroy the virus. Changes in the Spike protein may stop some antibodies binding to it, but likely not stop all antibodies binding to it. Our immune system also contains T-cells. T-cells can inspect our cells to locate infections and when an infected cell is found, they tell the cell to shut down to prevent the spread of the virus. A second type of T-cells can also inspect the B-cells to see what they are fighting – if it is a recognized infection, the T-cell can ramp up the immune response to the virus. The important point here is that the immune response is not triggered by the whole Spike protein, it is triggered by parts of it – essentially snipped up parts of the Spike protein string – so while mutations may change single building blocks in the whole string, the majority of the snipped parts remain the same (remember the 9/1,200 building block changes). So the vaccines may still prime our immune defenses, even though we face a new SARS-CoV-2 variant.

The effect of these Spike mutations on antibody binding is already being investigated for the Pfizer/BioNTech vaccine, so we should see data in a week or so on this. It’s also important to remember here that we have several vaccines already deployed and/or in clinical trials in areas with mutated variants, so we should be getting rapid feedback about if these offer protection against the new variant(s). I would also imagine there’s already a rapid movement to develop/trial vaccines against these new mutations. Fortunately these small genetic changes can be readily adapted into our existing vaccine platforms as these technologies were designed to be quite plug-and-play.

What does this mean for the rest of us now?

My PhD supervisor once told me ‘never think of biology as like stacking bricks‘ because the situation is always far more fluid than that. That’s what happened here: the game changed. “Tier 3” level restrictions may have kept the original SARS-CoV-2 in check, but will not contain the spread of this new variant and that is why this latest U-turn was absolutely needed, as painful/frustrating as it is. Personally, I would have made the same choice with my own Christmas plans. With the increased likelihood of this variant overwhelming the health system (and therefore increased fatality rate), this unfortunately means that anywhere this variant is spreading will likely rapidly head for “Tier 4 or Tier 5” equivalent restrictions (whatever that may be, but I would imagine towards schools closed in early 2021). The threat to health for the vast majority of people remains low, as long as we slow the spread so the health system can cope, but unfortunately this means another economic hit (and knock on effects on health/wealth/mental health).

In these situations people often look to find someone to blame, be it their government, some other country, some global conspiracy, 5G masts, etc. Historically, this is what happens in literally every pandemic ever and I’m really sorry to say this, but blaming others will not help… With the Christmas changes, it’s understandable for everyone to be frustrated, hurt, pissed off, and sharing posts about how pointless it all seems or complaining about how many things seem confusing – but sadly, that is not going to help either... If recent events have taught me one thing, it’s that it is far easier to spread confusion than it is to share knowledge – and that definitely doesn’t help… Complaining about a viral mutation won’t help any more than complaining about an earthquake or a volcano will. This is just what nature is like I’m afraid. The UK has been dealt a worse hand through the pure chance of evolution (remember the mutation could have gone the other way and made SARS-CoV-2 less deadly). As this virus is not aware of international boarders, maybe we should hope we are the only ones for now.

So what do we do? Well, probably be pissed off/hurt/angry and have a damn good complain first. But then we’ve got to accept that the game has changed, but the players are the same… SARS-CoV-2 just stepped it up another level, and the way we fight this is by bringing our A-game to following the rules. That is the only chance we have to avoid more painful restrictions on the economy and to keep people safe until enough people are vaccinated. Many bar owners, gym owners, artists, performers, shop workers, waiters/waitresses, and many, many more people beyond have already had their livelihoods crippled in Tiers 1-3 to protect the lives of many people who don’t even realise they’re the ones in danger if the health service is overwhelmed. Many others have been scared and lonely for months. Every one of us owes it to the sacrifices these people already made to do our part now and try to stop the spread. That means we keep calm, we find our resolve, and we follow the rules. Or to give a quotation my mum reminded me of the other day:

“It is not enough that we do our best; sometimes we must do what is required.”

Winston Churchill

The vaccines are still our way out of this nightmare, but the road there just got a bit longer. As always, the more of us that keep working together and following the rules, the easier it will be. We will come out of this. Together.


Next time, hopefully I can end this blog with something on vaccines. But for now, dig deep, stay safe, and maybe let’s try to share a positive message for Christmas.

2 thoughts on “Tier 4, mutant new-strain COVID

  1. Great piece, thank you. One question: you say ‘The UK has been dealt a worse hand through the pure chance of evolution (remember the mutation could have gone the other way and made SARS-CoV-2 less deadly)’ Do you mean ‘more deadly’?.

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    1. Thanks very much Peter! I did actually mean ‘less deadly’ – the virus could mutate to become more deadly, but actually the evolutionary pressure on it is to become more infectious and/or less deadly. If you think about a less deadly virus, potentially people would remain infectious for longer (as they don’t die) but also the decrease in pressure on the health service means we wouldn’t put as many restrictions in place to stop it from spreading (as I say, the key to understanding the whole situation is the health services becoming overrun). People can often have the impression this virus wants to hurt us, but actually it doesn’t (partly because it doesn’t want to do anything as it doesn’t think) – it’s in SARS-CoV-2’s best interest evolutionarily not to hurt us as it will spread further then.

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