COVID-19: What Do We Know About The New UK Strain?
by Raywat Deonandan, PhD
Epidemiologist & Associate Professor
University of Ottawa
(I add my credentials to these COVID-19 blog posts in case they get shared. I want readers to know that my opinion is supposedly an educated and informed one)
Well, 2020 is almost over, and of course COVID-19 throws us another curve ball to round out the year. The “new variant” that now dominates the news has arrived in Canada. Because I’ve had several media requests to comment on this development, let’s take a moment to take stock of what we know about this variant and what it might mean for our efforts to combat the epidemic.
What Is It?
First, what we are talking about here is a mutation of the virus SARS-Cov2, and not necessarily a change in the disease, COVID-19. This may seem like a pedantic distinction, but it’s really the crux of the matter. Remember: we attack the virus in order to control the disease.
You’re going to see lots of handwringing about the proper nomenclature –strain vs variant vs mutation. And frankly, even virologists seem to disagree about when to use which terms. So don’t worry about it. I’m sure I’ve used the wrong term at some point, and will likely continue to do so.
In general, a “strain” is like a new species. SARS-Cov2, SARS1, and MERS are all “strains” of coronavirus. Each strain has several “variants” that are different from one another, but not sufficiently so to warrant being their own strain. And each variant has its own set of specific “mutations”.
Here’s a clumsy analogy. I’ve got a series of mutations that give me brown skin. Millions of people have these same mutations. We are our own “variant” of human being that some people call a “race”. A chimpanzee has 96% the same DNA as human beings. Those 4% are sufficiently different to classify chimps as not a “variant” of human, but as another “strain” of primate. Make sense?
The important thing to note is that mutations –random changes to the genetic code of the virus– happen all the time. In your body right now, mutations are happening in multiple cells all the time. Most mutations are not beneficial, and will result in the cell or organism dying out. Some mutations are benign and will have no effect one way or another on whether or not the cell or organism thrives.
But occasionally a mutation occurs that is beneficial to the cell or organism. Beneficial in this context means that it confers an advantage upon the cell or organism, specific to its environment. Maybe the organism is in a warm climate, and the mutation allows it to function more efficiently in heat. In that case, organisms with that mutation are more likely to survive and to reproduce in such an environment than are organisms without that mutation. Over several generations, that slight advantage will mean that that mutation becomes more common in the warm climate.
There. I just described evolution by natural selection in purest Darwinian terms.
Viruses experience the same evolutional pressures, except in a much more accelerated time frame. A generation for us is measured in decades. For a virus, it could be hours or minutes. As a result, the more people who are infected with a virus over a longer period of time, the greater the probability that the random mutations that are happening all the time will eventually lead to one that confers an advantage for the virus. And given the rate of reproduction and infection, it’s likely that that new strain of virus containing the mutation will become more common, eventually becoming the most common strain, by virtue of its competitive superiority, or greater “fitness”, as the biologists say.
Virologists have identified several prevalent versions of the SARS-Cov2 virus. The one making the news is given the sexy and memorable name, “B.1.1.7” or “501Y.V1” or “VUI 202012/01” (ooh la la). It has at least 7 mutations identified in its genome. A regular PCR test doesn’t tell you if you’ve been infected with B.1.1.7 or another strain. You only know if the lab does a deeper investigation, or full genomic sequencing of the actual virus that infected you. In the UK, I believe about 20% of positive cases were thus investigated; statisticians extrapolate from that 20% sample to estimate the penetration of the new strain into society as a whole.
In September, they found 20-30% of positive COVID infections in London were in fact B.1.1.7 infections. By early December, it was up to 60%. I don’t think it’s untoward to conclude that B.1.1.7 is now the dominant strain of SARS-Cov2 in the densest parts of England, and possibly throughout the whole country.
“Fourteen-day COVID-19 case notification rates per 100 000 population in South East
England, UK, by reporting date as of 16 December 2020″
Source: https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spike-protein-mutations-United-Kingdom.pdf
Cases have since been detected in multiple countries, including Canada.
Where Did It Come From?
The working assumption is that the new variant emerged from random mutations while infecting human hosts in the UK. It is possible that infection among another animal host, such as minks, allowed for mutation, then was re-introduced into the human population.
Some suggest that a single patient who has a particularly weird immune system, and who is infected for a very long time, could theoretically be host to multiple problematic mutations. This is because immunocompromised people tend to have a variety of additional chronic conditions. Such a person infected with SARS-Cov2 might see the coronavirus linger for months, giving it many opportunities to mutate, replicate, and, frankly, evolve. Here’s one such story.
The more conspiracy minded have even suggested that this emergence is the result of our vaccination efforts. They argue that by making the population immune to the dominant strain, we have unlevelled the environmental playing field in favour of the new strain. The European CDC discounts this theory since, “the observed increase [in new variant cases] does not match the timing of [vaccination] activities.”
Frankly, I don’t think it matters much where it came from, except to the extent that such knowledge might empower us to monitor the emergence of future variants.
What Are Its Properties?
It is being reported that B.1.1.7 is up to 70% more transmissible than SARS2-Classic (as I will call the original SARS-Cov2 strain in this article). It is unclear if this is because (a) changes in the proteins on the surface of the virus (the famous “spike protein”) make it better able to bind to the host’s cell and therefore achieve infection; or (b) changes to the exterior of the virus make it better able to evade the host’s immune system, and therefore allow the virus to more easily achieve infection and/or disease.
I say it is “unclear”, but maybe it isn’t. To get into the genetic woods, the specific mutations of B.1.1.7 that are concerning are:
- N501Y, which allows it to bind tightly to human host cells, and allows greater infectivity in animal models
- D614G, which might allow better transmissibility and maybe even viral load, at least in animal studies
- 69-70del, which might allow the virus to evade the immune system
So while the epidemiologic data is not conclusive, all signs point to this variant being more transmissible. This greater transmissibility increases the reproduction number (r) by 0.4. You will recall, I hope, that “r” is the average number of new cases produced by an old case. If r=1 then the epidemic is in steady state. If r>1 then we have exponential growth. And if r<1, then the epidemic is diminishing. If you follow the daily estimates of “r” in your community, you will know that we struggle to achieve changes of 0.2 or 0.3. A biological change conferring an increase as much as 0.4 is not great for us. More on this later.
Is It More Serious?
So far, there is no evidence that B.1.1.7 is any more or less lethal than SARS2-Classic. Nor is there any evidence that people who are infected with it are more or less likely to get sick or any different kinds of symptoms.
However, even if the new variant is not more likely to make you sick or kill you, the fact that it is more transmissible might still increase population-level morbidity and mortality statistics. This is because greater transmissibility means the infection is more likely to make its way into more vulnerable populations (i.e., the elderly) who are more likely to be hospitalized and die.
This is, I think, an important statistical nuance that might confuse people looking just at the community-level numbers. So I’ll say it again. The arrival and fast penetration of B1.1.7 might be accompanied by an increase in hospitalization and death rates, which might increase people’s fear. However, unless clinical data suggest otherwise, such an observation does not necessarily mean that the risk of severe illness and death to a given individual has changed. Rather, it would most likely mean than the virus is finding easier access to people who should be better protected.
This is why “lethality” has subtly different meanings depending on whether you’re looking at it from a population or an individual perspective.
Keep in mind, though, that all the information we have about B1.1.7’s effect on human health is among patients under 60 years of age. So we don’t know if it is less or more serious among older people. Despite rumours, It’s also unclear whether the new variant is more or less able to penetrate the immune systems of children; but there is zero evidence –that I am aware of– that suggest that the incidence rate is any higher among children.
Frankly, my biggest concern is for the panic that news of this variant is now stoking amongst people. The word “mutation” is scary. But over time, with enough opportunity for infection and mutation, selective pressures can drive pathogen evolution toward less lethality. This is because diseases that do not readily kill their hosts have a better chance of remaining prevalent than ones that kill off their hosts before they get a chance to spread infection further. (Nothing is 100%, of course; this is a broad observation and certainly not a biological rule.)
This is not to say that SARS-Cov2 is bound to mutate in that positive direction if we only give it a chance. Rather, my point is not to be overly scared of mutations. It’s possible to get a less serious disease from mutation. Mutations are to be expected. And frankly, the best way to prevent or slow the emergence of future mutations is to prevent transmission in the first place. If the virus cannot infect new hosts, then it cannot replicate, and will be denied opportunities for evolution.
Will The Vaccines Still Work?
This is the big question. And so far, all signs point to YES. The vaccines will still work against B1.1.7. This is because all of the licensed vaccines work in much the same way: they train the immune system to identify the spike protein on the surface of the virus. And even though a handful of mutations are actually on the spike protein, the protein does not seem to have changed so much that the antibodies aren’t able to identify it.
In an earlier post, I likened the spike protein to a “license plate.” The vaccine teaches your body to identify the license plate so it knows when that particular vehicle is coming. The mutation might have smudged one corner of one of the digits on the license plate. But it’s still pretty clear what’s written on the plate.
The official statement by Moderna is: “The full-length Spike protein is 1,273 amino acids long, so while recent variants involve multiple mutations, for instance up to 8 amino acid changes in the spike protein of the B1.1.7 strain, these represent less than a 1% difference from the spike protein encoded by Moderna’s vaccine.”
And: “the broad range of potential neutralizing antibodies made possible by the Moderna COVID-19 Vaccine provide confidence that our vaccine will also be effective at inducing neutralizing antibodies against them.” Of course, the vaccine manufacturers are frantically running tests to confirm this supposition. But I’m not too worried.
But here’s an important nuance. The new mRNA vaccine technology is magical for a number of reasons. One of these reasons is that it took about 48 hours to create the Moderna vaccine, once the virus genome had been sequenced. These past 10 months were spent testing and verifying the effectiveness and safety of the vaccines.
This means that if a new variant of SARS-Cov2 emerges that is significantly different from SARS2-Classic, it would only take 48 hours to create a new perfectly matched vaccine. The rate-limiting step at that point would be in manufacturing and distributing the doses. It would likely not have to go through the lengthy administrative licensing process that we just watched for the first batch of vaccines, since the platform has been shown to be effective and safe. We deal with a similar challenge every year with the seasonal flu vaccine, which is always a new formulation.
So I am not worried about B1.1.7 jeopardizing our vaccination plans. Still, let’s vaccinate everyone ASAP just to make sure.
So Is It A Big Deal?
Well, a new more transmissible variant is not great news. It means it just got a little harder to control community transmission. And as we all know, we haven’t been doing a fantastic job of that in many parts of our society.
Even if lethality (as measured by the case fatality rate or the infection fatality rate) does not change, the prospect of more people becoming infected does suggest that more people will die. A strain with more transmissibility does suggest a greater load on our health care system. So limiting community transmission is even more important.
My biggest epidemiological concern, frankly, is what it means for herd immunity. As noted above, the increased transmissibility translates to an increased in “r” of about 0.4. Recall that the goal of widespread vaccination is “herd immunity”, which is that magical effect that occurs when sufficient people are immune, such that those who are not immune are unlikely to ever be exposed to the disease.
Modelling based upon current estimates of the reproduction number suggest that we can get to herd immunity when 70% of the population has achieved immunity via vaccination. With an increase in “r” from the new variant, that threshold goes up to about 73%. So our job got harder.
What Do We Do?
Nothing has changed in terms of what we need to do. We have to slow or stop transmission. This is because transmission allows the new variant to enter our population faster. Transmission allows the new variant to gain faster entrance to our vulnerable population. Transmission allows greater opportunity for more mutations and therefore the heightened likelihood of a variant emerging that is indeed resistant to our vaccines. Transmission bad.
We know how to slow transmission: wash your hands, wear a mask, keep your distance, don’t interact with people you don’t live with, don’t go into buildings you don’t need to go into.
And, most importantly, we need to get vaccination shots into as many arms as we can, as quickly as we can.
Anything Else?
Yes. As with all scientific things I write about, and as with all things in science in general…. “all of this is true until further notice.”
In other words, stay tuned. Things change as new information becomes available.
In the mean time, we keep doing the same things to keep ourselves and our communities safe. And we continue to celebrate the miraculous salvation of the new COVID vaccines, which remain our best chance for normality in the near term.
