Since the start of the pandemic, SARS-CoV-2, the virus that causes Covid-19, has been mutating, its genetic code slowly changing as it spreads from person to person across the globe. For most of that time, the mutations didn’t concern scientists. The genetic changes didn’t seem meaningful in terms of how dangerous the virus is. Mutations are normal. Some even weaken the virus.
Now, things are different.
There are three mutated variants of SARS-CoV-2 of particular concern around the world. Researchers do not have the same level of evidence for each: One is more well understood than the others. But in each case, researchers see a seed of something concerning.
There’s B.1.1.7 (yes, all these variants are clunkily named). This variant was first detected in the UK in September. Scientists strongly suspect it’s more transmissible (i.e., contagious) than past versions of SARS-CoV-2, and there’s some preliminary evidence that it might be slightly more deadly.
Then there’s a pair of variants — one discovered in South Africa in October, and another in Brazil in December — that are less well understood. But scientists are beginning to suspect that they might have evolved ways to evade the human immune system, at least a little bit.
A reasonable question you might be asking: Why now? Why have these three variants of concern popped up in such quick succession? The fact that the virus is mutating isn’t new. It’s been mutating all along.
“We’ve had many, many variants in SARS-CoV-2 for a long time now, and scientists have even been tracking these in fairly detailed ways since the summer of 2020,” Emma Hodcroft, a molecular epidemiologist at the University of Bern, says. “The big difference is that, before December, we hadn’t really seen any variants that seemed to be behaving any differently.” (By “behaving differently” she means that the virus itself didn’t seem at the time to be more infectious, or more dangerous in any intrinsic way.)
Hodcroft and others who study the evolution of viruses provide a few overlapping answers to the question “Why now?” None of them perfectly explain what’s going on.
But thinking through them brings us to another, perhaps even more critical question: How might the coronavirus continue to evolve? Will even more variants emerge that challenge our fight against the virus? And what does that mean for the pandemic?
Overall, experts outlined four reasons we’re seeing these variants now. And it all boils down to one thing: evolution.
Reason 1: The virus’s genetic diversity increases over time
First off, it’s helpful to get a refresher on how evolution works. At its core, evolution requires two things: individual differences and natural selection. Evolution is a nonstop process. Organisms — as a group — accumulate change over time through mutations, and the environment helps determine which changes stick around in a population, and which become less prevalent.
Viruses mutate because they’re constantly making copies of themselves in enormous numbers. If you were writing a draft of something millions of times on a computer, extremely quickly, you’d probably make some typos. This has happened millions and billions of times across the globe. The longer the pandemic rages on, the more chances the virus has to evolve.
In the beginning of the pandemic, the viruses infecting people were really similar to one another, because they weren’t that far removed from the original virus that began the outbreak. But now the virus has been changing genetically over the past year, branching out like a family tree. So many genetic changes have accumulated, in different places.
“We have no evidence that the underlying mutation rate is changing,” Sarah Cobey, an epidemiologist who studies viral evolution at the University of Chicago, says. The virus is still making its typos at the same rate. It’s just that those changes start to accumulate the longer the pandemic continues. If you kept copying a book, over and over, making typos in each copy, you’d end up with a somewhat different book than you started with. Likewise, according to Cobey, you’d expect the genetic diversity of the virus to increase over time.
So that’s one major part of it. The virus has just had a lot of opportunities to become something slightly different.
But that’s not all of it. The increased diversity doesn’t quite explain why we’re seeing these particular — seemingly more concerning — variants at this particular time. “We are seeing evidence of adaptive evolution,” Cobey says. These variants appear to be either getting better at infecting people or possibly evading the immune system, and they are doing so in similar ways.
Genetic diversity alone doesn’t explain that. Natural selection does.
Reason 2: It’s possible the virus is evolving in response to increasing human immunity
The virus’s increasing genetic diversity only explains part of the story. The other part of the story: natural selection.
Some of the virus’s genetic changes provide an advantage, which has led, in some cases, to these variants outperforming older strains of the virus. “Some of those [genetic] substitutions are actually helping the virus replicate better,” Cobey says, which then can lead to the variants infecting an increasingly larger proportion of people compared to other variants.
Both the P.1 variant found in Brazil and the 501Y.V2 variant found in South Africa have a mutation called E484K, which changes the part of the virus that attaches to human cells (it’s also the part that the immune system most readily recognizes after someone is vaccinated). That mutation, Hodcroft says, “might allow reinfection.” In other words, people who have already been infected with SARS-CoV-2 could potentially be a little bit more susceptible to these variants (though this is still not confirmed).
Hodcroft suspects that both the P.1 and 501Y.V2 variants may have evolved in response to human immunity. And she stresses: What follows is mostly speculative at this point.
In the beginning of the pandemic, no human had been exposed to SARS-CoV-2 before. That means everybody’s immune systems were equally bad at recognizing the virus. If there had been a variant that was good at evading the human immune system, it wouldn’t have risen to prominence because it wouldn’t have outperformed its viral peers.
As Hodcroft explains it: “Even if this [E484K] mutation popped up — which we know it did, we can see that it popped up a few times — it might not have been in a place where this was an advantage.”
In many places around the world, there are lots of people who have already been infected and who have developed some level of immunity to the virus.
So now, variants that can evade the immune system have an advantage. They could grow and replicate where other variants cannot. And that variant could quickly become the dominant one.
“I want to be really clear: We aren’t 100 percent sure, scientifically, that this is what’s happened,” Hodcroft says. “But these are the kinds of things to think about when we think about why we might be seeing different variants now. We’ve changed the rules of the game.”
Reason 3: The virus has spread so far that rare things are starting to happen
The longer the pandemic goes on, the more chances there are for rare — and sometimes consequential — things to happen.
The B.1.1.7 variant might be one of these consequences. It appears to have acquired significant genetic changes over a short period — so many that scientists suspect the variant might have emerged in an immunocompromised person.
In most people, Hodcroft explains, the immune system mounts a full-on assault on the virus, eliminating it in a couple of weeks. “In people that have compromised immune systems, though, there’s a very different dynamic,” she says. “So, for one thing, the virus could be in them for months instead of weeks.” That gives the virus more time to evolve, to accumulate mutations that might make it easier to thwart the immune system.
Many things have to happen for this to occur. Not only does an immunocompromised person have to get the virus (and many immunocompromised people are being particularly cautious), the virus would have to acquire mutations, and then the immunocompromised person would have to spread the virus to another person.
“These are all like ‘super-edge cases,’” Hodcroft says. But “by keeping cases so high, you increase the chance that sooner or later, you’re going to hit that jackpot ... we keep rolling the die when we keep the cases up so high.”
Reason 4: Some Covid-19 treatments might have instigated some evolution
The rise of these variants “may have something to do with the use of convalescent plasma,” says Michael Worobey, the head of the department of ecology and evolutionary biology at the University of Arizona.
Convalescent plasma treatments are blood plasma transfusions from people who have recovered from SARS-CoV-2. The idea is that along with the transfusion come antibodies that can help someone else with Covid-19 fight off the disease. The problem is that within certain recipients, the plasma could conceivably also create an environment that favors a stronger variant of the virus.
“So there are cases where the identical [mutations] that characterize the UK variant have also evolved in patients who are chronically infected with the virus and were then given convalescent plasma,” Worobey says. “It’s a perfect storm.” The virus has built up genetic diversity in the patient, and then the convalescent plasma acts as a force of natural selection, choosing among those variants one that could evade antibodies in that plasma.
Worobey is not saying that this definitely happened with the B.1.1.7 variant, just that it’s possible. (A similar thing, he says, could have happened with using monoclonal antibodies — synthetic antibodies produced as a Covid-19 treatment — on immunocompromised patients.)
It’s not that these treatments never should have been used. In many cases, they may have helped save lives when there are few treatment options for Covid-19. But in the case of using convalescent plasma on immunocompromised people, Worobey says, it may have been “a bit irresponsible.”
The virus will keep evolving. Vaccinations need to happen quickly, and cases need to decrease.
The virus will keep changing, and there will be more variants. Not all will be variants of concern, though.
“I think one thing that we definitely have to keep in mind, particularly in the next few weeks and months, is that a lot of people are now very interested in doing [viral genetic] sequencing and looking for variants,” Hodcroft says. “And that’s fantastic. This is exactly what I’ve been kind of begging for for a long time — for more countries to really dedicate resources to this.” But with the increased vigilance, she says, “we’re going to see a lot of false alarm variants.”
But there also might be more variants of concern in the near future, as the virus is about to get hit by another big selection pressure: vaccines.
If, due to random mutations, there’s a strain of the virus that is just a little bit better at evading the immunity provided by vaccines, it could spread.
That’s why these viral evolution experts want vaccination to happen as fast as possible. Just as partial immunity in a single immunocompromised person can act as a selection pressure for evolution, partial immunity in the population at large can as well.
“What we don’t want is for there to be high levels of virus circulating and spending a lot of time with a partially vaccinated population,” Hodcroft says. “We want to keep case numbers while we’re vaccinating as low as we can.”
That’s because “once you vaccinate hundreds of millions of people, the virus is going to be under really quite intense pressure to evolve [immune] escape variants,” Worobey says. Some of these variants, he warns, “may already be in existence” among the public but have not yet been detected — or may soon form as the pandemic continues. “And those variants, I think, we can expect to sweep up to much higher frequency once vaccination provides this huge selective force.”
Evolution happens when there’s a lot of genetic diversity, which then meets a selection pressure. This is what’s happening as the pandemic continues during a vaccination campaign.
The good news is that, for now, it appears the existing vaccines will still be broadly effective against the variants, and that it’s possible to update the vaccines to account for future changes. But how can we stop more viral evolution from happening in the first place?
“The best way to avoid it is to go back in time and not allow the pandemic to spin so out of control,” Worobey says. “If we had done that, and then vaccinated, then we would have been in a much less dangerous situation.”