Health officials in the United Kingdom and around the world are worried about a new, seemingly more contagious variety of SARS-CoV-2 (the virus that causes Covid-19), which has emerged in the country and was announced over the weekend. The evidence that this new strain spreads more easily between people is not rock solid, but it’s concerning enough to have forced dramatic action.
Nations are already shutting down travel from the United Kingdom, where the new strain, known as B.1.1.7 (we’ll call it the UK variant, for simplicity’s sake), is rapidly spreading in the southeastern part of the country. Within the UK, officials are imposing stricter limits on movement and public spaces.
Right now it doesn’t appear as though the new UK variant of SARS-CoV-2 is more dangerous in individuals. It doesn’t seem to make people sicker, nor is it more likely to kill them. “I think the key point is that there is no evidence now … that this virus is more pathogenic — creates more problems, more morbidity and mortality — than the previous virus,” Moncef Slaoui, the scientific lead for Operation Warp Speed, said during a Monday press conference.
What it does appear to do, at least based on preliminary evidence, is spread more quickly among people. That alone is a problem: The coronavirus spreads fast enough as it is. Compounding concerns is that the UK variant echoes a similar story in South Africa, where a strain called 501.V2 has become the dominant version among new cases of the virus. Scientists are wondering whether that strain is more transmissible, too.
The virus has been continually changing its genetics through the course of the pandemic. That’s what RNA-based viruses like SARS-CoV-2 do — they mutate. Most of the time, the mutations mean nothing. But this time, something is different.
“I’ve spent a lot of time this year reminding people that mutations are normal,” molecular epidemiologist Emma Hodcroft, who works on a project called Nextstrain, said. For the entire pandemic, scientists the world over have been feeding Nextstrain sequences of the virus, and Hodcroft and her colleagues have been tracking its genetic changes closely.
In the past, mutations haven’t warranted big newspaper headlines. “I’m now finding myself singing a slightly different tune,” Hodcroft said. This time, there does seem to be evidence that the new strain is something worth being vigilant about. “We probably should consider taking some precautionary measures while we’re trying to find out more,” she added.
At the same time, Covid-19 is surging around the world, even without these new mutations. Scientists are still trying to figure out what these new variants of the coronavirus actually mean for the pandemic. It’s also unclear where else the UK variant may have already spread. “The variant could already be in the United States without having been detected,” the US Centers for Disease Control and Prevention reported Tuesday.
The good news is that we already know how to respond to these new variants: in the same way we’ve been responding to the pandemic overall. The virus still transmits primarily through viral-laden breaths in the air. Mask-wearing, social distancing, and good indoor ventilation are as critical as ever.
There’s a lot about this story that’s potentially very alarming, or confusing. And the story is not yet complete, as scientists need more evidence to understand whether these new variants pose a new threat.
To add some clarity, here’s what researchers have learned so far. Let’s start with the basics.
Viral mutations, explained
Viral mutations. New strains. Increased transmission. It all sounds like scary science fiction. But to demystify things, and to understand why scientists are a little concerned about this new variant — and why most variants don’t faze them — it’s worth understanding how viruses mutate in the first place.
“Oftentimes, I think the word mutation in general conjures up a lot of things in people’s minds, like, you know, Ninja Turtles or X-Men or cancer, like zombie apocalypse-type stuff,” Angela Rasmussen, a virologist with Georgetown’s Center for Global Health Science and Security, said. “A mutation is just a lot more mundane than that.”
Viruses mutate because they’re constantly making copies of themselves in enormous numbers. To accomplish this, they have to hijack the hardware of a host cell that they infect. However, this process can be a bit sloppy.
Within a human body, a virus can replicate itself millions or billions of times, Hodcroft explains. If you were writing a draft of something millions of times on a computer, extremely quickly, you’d probably make some typos. That’s what’s happening with the viruses. “They make a typo” in their genetic code, she says. One letter of their ribonucleic acid (RNA) chain is replaced with another.
Viruses that use RNA as their genetic material, like SARS-CoV-2, are particularly vulnerable to mutations since the RNA molecule itself is more unstable than DNA. The process of copying RNA is also more prone to error.
These typos can be very useful for scientists because they happen at a regular rate, and are passed down through generations of the virus as it spreads through a community. Often, scientists can use these subtle changes to trace certain strains’ lineage and their spread through a population.
The majority of these typos are inconsequential when it comes to human health. “One typo, or even a few typos, doesn’t usually change how the virus works,” Hodcroft says. Some even harm the virus. “You’re much more likely to break it than to make it better” when it comes to mutations, she says.
But in rare instances, some mutations can give a virus an advantage, like allowing it to infect cells more readily or spread among people faster. Those mutant strains can then become dominant within a population.
That might be what we’re looking at here with the UK variant; this new strain may have accumulated typos that could make it more easily transmitted between people.
Four lines of evidence converging on this new mutation being more transmissible
So why do scientists think this variant is more transmissible?
They don’t have this nailed down yet for sure, but four converging streams of evidence are all pointing in the same direction. “That’s making people feel like maybe there is something here to be worried about,” Hodcroft says. “Each one of these things on their own, I would say is not necessarily convincing.” But all together, they paint a concerning picture.
One is that in the areas of the UK where this new variant is spreading, it is accounting for a larger proportion of new cases. “What this implies is that this new variant is spreading better than other variants that are circulating in the same region,” she says.
National testing data shows increased prevalence of the variant in positive cases over time. This is detected incidentally by the commonly used 3-gene PCR test because 69-70del leads to a negative signal. But this does not effect the results of the test. 7/
h/t @The_Soup_Dragon pic.twitter.com/aPpAjjb35W
— Muge Cevik (@mugecevik) December 21, 2020
A second is that the increase didn’t co-occur with any overly obvious change in human behavior. “We don’t really have strong evidence that everyone in the southeast [UK where this variant is spreading] has just ripped their masks off and is, you know, totally violating restrictions,” she says. That said, it could be a coincidence. It could be just that people who happen to have contracted this variant have it are spreading it more often via their behavior.
After all, “this new variant has emerged at a time of the year when there has traditionally been increased family and social mixing,” according to the European Center for Disease Prevention and Control, which estimated that the transmissibility of the new variant has increased by 70 percent compared to prior versions of the virus. (Both Rasmussen and Hodcroft say the 70 percent more transmissible figure is most likely an overestimate.)
Third, there’s some early data about how this variant acts in Covid-19 patients. “There may be slightly higher viral loads in patients with the variants,” Hodcroft says, suggesting the virus has an easier time replicating in the body. (Viral load refers to the amount of virus in the patient. Rasmussen also cautions that viral load data is really sensitive to timing and when the patient was sampled in the course of the illness, so there needs to be more data to confirm this.)
Finally, the genetic changes in the UK variant mirror changes in the South African variant, which has also been associated with rising case numbers. That makes a plausible link: that this particular genetic change may be behind the increased transmissibility in both variants.
However, this is still short of definitive confirmation that the new variant is more transmissible.
According to Slaoui, figuring this out for certain would require laboratory animal testing to see how easily the virus can spread from one organism to another. But this testing can take several weeks.
In the face of that uncertainty, many urge caution.
Again, there’s still no evidence this new variant causes more severe disease. The evidence only points to increased transmissibility. But a more transmissible virus is still a concern. “In general, the more people get infected, the number of hospitalizations and deaths rise accordingly as a proportion of that number,” Hodcroft says. “So more cases is also bad news.”
What does the mutation … do?
The UK variant of SARS-CoV-2 actually contains 23 mutations in the genome of the virus. “We don’t really know what they do,” Rasmussen says. Individually, many of these mutations have already been seen in other strains of the virus around the world. But the combination of these changes in a single virus could be making the new variant more likely to spread.
However, scientists do think that some mutations may be more important than others, and there are several mechanisms by which mutations could make the virus more infectious. Those include:
1. The virus could end up with changes to its spike protein that allow it to enter cells more easily.
2. The virus could develop a mechanism to replicate more quickly inside a body, which would lead “to people becoming infectious faster, or contagious faster than they would with another variant,” Rasmussen explains.
3. The virus could theoretically have evolved an ability to counteract the cell’s innate immune defenses, making it easier to infect that cell.
One of the pathways scientists suspect may be at work stems from the N501Y mutation, where the amino acid asparagine is replaced by the amino acid tyrosine in the 501st position of the viral protein sequence. It’s one of several mutations in the virus’s spike protein in the UK variant, but N501Y is in the part of the spike that actually comes into direct contact with human cells. The same mutation has been found in the South African variant of SARS-CoV-2 that’s also quickly spreading.
Since the virus attaching to a host cell is critical to the virus’s reproduction, the virus’s spike protein is especially important — and delicate.
“If you were just making random changes in the lab, almost any change you make in that area would result in just a dead virus that can no longer get into the cell,” said Benjamin Neuman, a virologist at Texas A&M University Texarkana. “That fact that this thing is able to spread at all tells you that it’s at least as good as the original version. The fact that it’s spreading faster may indicate that it’s a little bit better at grabbing on to host cells, which is the first step of the entry process.”
But this particular N501Y mutation has already been detected in strains that have risen and fallen in other parts of the world over the course of the pandemic. So it may be that the other mutations coupled with N501Y are having some sort of compounding effect. And scientists still need to do more work to determine if this is actually what’s causing the rise of the new SARS-CoV-2 variant in the UK. Finding out the answer could help researchers come up with ways to counter this variety of the coronavirus.
How did these coronavirus mutations happen?
Scientists don’t know exactly how the UK variant came to be. But there may be a clue. Hodcraft is struck by the sheer number of mutations in the UK variant — 23 in all — which makes her suspect it’s possible this variant arose in an immunocompromised person. “It’s an above-average number of mutations,” she says.
In most people, she explains, the immune system mounts a full-on assault on the virus, eliminating it in a matter of 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.
“It’s one scenario,” she says. “We may never know exactly what happened here.”
The basic truth: The more this virus spreads, the more chances there are for dangerous new variants to emerge. In any person — or animal, for that matter — the chance for a dangerous new variant to arise is rare. But rare things can happen when there are so many cases: more than 77 million confirmed cases worldwide.
Since viruses like SARS-CoV-2 are mutating and since Covid-19 has spread in so many people, it’s theoretically only a matter of time before a certain set of mutations align in a way to give the virus a boost.
What can we do about Covid-19 mutants?
To stop mutations, quite simply, we need to stop the spread of SARS-CoV-2 in general. For one, that helps us deal with the pandemic overall. But “that’s also conveniently how we get fewer emerging variants,” Rasmussen says. “If the virus isn’t replicating, it can’t mutate. And if it can’t mutate, the new variants can’t emerge.”
We fight the new variant as we would any variant of SARS-CoV-2: with masks, with social distancing, with good hand hygiene. “I don’t think people should be panicking,” Hodcroft says. “Lower case numbers, no matter what the variant, are better.”
It’s already been said but if we actually follow protocol and have policies that support those protocols a new variant that is more transmissible would be combatted just as an older variant. So like worry less about mutants and more about masking and distancing and vaccination.
— K. Taylor, Ph.D., M.S. (@KYT_ThatsME) December 21, 2020
Scientists have one more tool, though: genetic tracking. At Nextstrain, Hodcroft and her colleagues receive viral genetic sequences from all over the world to try to paint a real-time picture of transmission chains and keep tabs on how the virus is changing. But not every place in the world is providing the same amount of data.
The UK does a lot of viral sequencing, for instance. It was able to pick up on the new viral strain quickly because of that. In other locations around the globe, that might not have happened so fast.
“In the US, it’s a really spotty picture,” Hodcroft says when it comes to sequencing. “Some states have really invested in sequencing; some states haven’t. So for some states, we probably have a fair idea of what’s going on. In other states, we really don’t have many sequences.”
Overall, the CDC reports that the US has only sequenced 51,000 of the 17 million cases reported here. That’s .07 percent. In comparison, the UK aims to sequence 10,000 virus per week, and plans to increase that capacity further (In addition: The UK sequences the genomes faster than the US, according to infectious disease researcher Trevor Bedford.) That lack of viral genetic testing creates a big blindspot in the US. The UK variant could have already arrived here undetected “given the small fraction of US infections that have been sequenced,” the CDC states.
More sequencing, overall, would lead to the faster detection of new strains and faster means to contain them if they were deemed problematic.
Do mutations mean a Covid-19 vaccine won’t work anymore?
With new mutations, there is a concern that a new strain of SARS-CoV-2 could arise that would be different enough from previous versions such that prior exposures — whether through a vaccine or an infection — won’t offer protection. So, yes, it’s possible that the coronavirus could someday mutate in a way that would elude a vaccine or previous immunity.
Right now, though, scientists think this UK variant would still fall under the same umbrella of protection as earlier strains. If someone received a Covid-19 vaccine for an older generation of the virus, they would likely have protection against this one.
To explain why, it helps to understand how the immune system deals with viruses. When the human body detects a hostile foreign entity like a virus, it starts to produce antibodies (proteins that attach to the virus or to infected cells). Antibodies can then interfere with how the virus works. They can also flag the virus or virus-infected cells for destruction by other immune cells.
The specific places where the antibodies attach to the virus are called epitopes, and most Covid-19 vaccines target epitopes on the virus’s spike protein (which is what the virus uses to attach to human cells and enter them).
“The good thing with the vaccine is that it induces an immune response against several epitopes that have been mapped around the spike protein,” Slaoui said. “The chances that one set of mutations would alter all those epitopes, I think, are extremely very low. The expectation, scientifically, is that these kinds of variations are unlikely to escape fully the protective response by the vaccine.”
More good news: Scientists at the University of Texas Medical Branch have announced (via a tweet) preliminary evidence that antibodies that neutralize the more common strain of the virus also neutralize a strain with the N501Y mutation (the one that impacts the part of the virus that comes into direct contact with human cells, as mentioned above). That suggests that an immune system primed — by a natural infection, at least — to fight the old variant can also fight one with this specific mutation.
Some good news (and incredibly fast work) on one of the mutations scientists are worried about: N501Y.
In these lab experiments serum from recovered #covid19 patients was just as good at neutralizing virus with the mutation as without it. https://t.co/SIxfo2x3qp
— Kai Kupferschmidt (@kakape) December 22, 2020
Texas A&M’s Neuman noted that there’s also evidence right now showing how well vaccines can protect against mutated forms of the virus in clinical trials. Many of the vaccines being administered were engineered to counter the earliest generations of SARS-CoV-2 but are still showing themselves to be highly effective against Covid-19 caused by more recent versions of the virus.
“All the tests are being done, all the papers being published, are being done with current strains, which have several mutations relative to [the first iterations of the virus], and it does still seem to be working,” Neuman said.
Covid-19 vaccine developers say they are keeping a close eye on these changes and testing to make sure their vaccines are still effective. “In terms of the new variant, Pfizer and BioNTech are monitoring SARS-CoV-2 sequence changes and the companies are working to generate data on how well serum from people immunized with [the Pfizer/BioNTech vaccine] may be able to neutralize the new strain,” said a Pfizer spokesperson via email.
And the new Covid-19 vaccines are well-equipped to adapt. The two that have received emergency use authorizations from the Food and Drug Administration — the Pfizer/BioNTech vaccine and the Moderna vaccine — both use mRNA as their platform. These vaccines deliver the instructions for making the spike protein of SARS-CoV-2 to human cells. Those human cells then manufacture the component themselves, allowing the immune system to use it to prepare for an infection. One huge advantage of this approach is that the mRNA sequence can be altered quickly; the first such vaccines for Covid-19 were developed within days after the genetic sequence of the virus was posted online.
Could manufacturers like Moderna or Pfizer/BioNTech then retool their vaccines to target the new variants without going through the whole tedious clinical trial process again?
Possibly, according to Jesse Goodman, a former chief scientist at the FDA and a professor of medicine at Georgetown University. He told Vox that vaccines for new variants of the influenza virus are approved every year without large-scale trials. New versions of a Covid-19 vaccine to accommodate mutations similarly might not need another round of study in tens of thousands of people, but may require some testing to figure out dosing and immune response. With such a new virus and brand new vaccines, the regulations for these situations have not yet been laid out.
Should we expect more mutations in the future?
Short answer: yes.
The UK and South African variants are unlikely to be the last to make headlines. Coronavirus is constantly evolving. We should expect it to keep changing slightly.
“There will be new variants that emerge,” Rasmussen says. The thing is, with each new significant strain, scientists will have to do careful work to determine whether it’s more dangerous.
And there are some mutations we can perhaps even expect — if not in the coming weeks, over the next several years.
Recently, virology researchers at the Fred Hutch Cancer Research Center published a preprint (i.e., not yet peer-reviewed) study, looking at how a coronavirus that causes the common cold evolved from the 1980s onward. To accomplish that, they got old blood samples, which included antibodies that cling to this particular virus. They also reconstructed pieces of the cold virus from other eras. Basically, they wanted to see if older blood could still neutralize newer virus. If it couldn’t, that would indicate the virus has evolved over time to evade the immune system.
Here’s what the researchers found: “This other human coronavirus does indeed evolve over the course of multiple years to gradually escape human immunity,” Jesse Bloom, a virologist who co-authored the study, says. “So we think this suggests that there’s the potential for SARS-CoV-2 to do the same thing.” But Bloom stresses that this process takes years. It’s enough time to prepare, to monitor, and to potentially tweak vaccine formulations to keep up with the virus’s evolution.
It’s not like the virus can evolve into an entirely different beast. “It can mutate to maybe escape antibodies,” Rachel Eguia, the study’s lead author, says. But it can’t change so much that it alters its own ability to enter cells.
Scientists are also keeping their eyes out for a rapid, major mutation event known as recombination. That’s where an individual is infected with two different strains of the virus at the same time, allowing the virus strains to swap parts. These new viruses could then evade the antibodies that targeted their predecessors. Some researchers think that recombination might be how SARS-CoV-2 originated in the first place.
“This is all hypothetical in this particular virus, but it happens in other viruses all the time,” Neuman said.
Faced with these looming challenges, reducing the transmission of the coronavirus in general is still the best way to protect the fragile progress made in the Covid-19 pandemic so far. Reducing transmissions is also one of the best ways to make sure powerful tools like vaccines remain potent for as long as possible. The fact that multiple Covid-19 vaccines are coming out is not a cause for complacency, and these new variants of SARS-CoV-2 highlight how important it is to remain vigilant.
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