Q: What are the risks of the newly identified coronavirus variants?
A: It’s not yet known whether mutant versions cause more severe disease, but some are likely more contagious. Scientists expect vaccines will work but are monitoring the situation.
FULL QUESTION
Subject: COVID-19 Mutation in Colorado
I know that viruses continuously mutate, but is this new mutation that was just found stateside actually more dangerous than any other mutations of the COVID-19 virus?
FULL ANSWER
On Dec. 29, Colorado officials reported the first confirmed case of COVID-19 in the U.S. due to a variant of the coronavirus that emerged in the U.K. in September.
Known as the B.1.1.7 lineage variant, but colloquially called the “U.K. variant,” the strain has spread rapidly in Britain, and scientists believe one or more of its nearly two dozen mutations have made the virus more transmissible.
A mutation is just one change to the genetic sequence. A variant usually has multiple mutations, making it a distinct virus. (To avoid stigma, we are not referring to the variants by their places of original identification.)
Meanwhile, another variant — dubbed the B.1.351 lineage variant and also referred to as 501Y.V2 — independently cropped up in October in South Africa. It shares a key mutation with B.1.1.7 and is also likely more infectious. Among numerous other genetic changes, B.1.351 has another mutation of interest that might allow it to partially evade immune responses in some people already exposed to the virus.
Researchers have also flagged another potentially concerning variant in Brazil, known as the P.1 lineage variant, that shares some of the mutations present in B.1.1.7 and B.1.351 and was observed in travelers to Japan.
There is no firm evidence yet that any of the variants cause more severe disease, although this is an active area of study.
As of Feb. 4, B.1.1.7 has been detected in 73 countries and at least 33 U.S. states, while B.1.351 has been observed in 32 nations and was first reported in the U.S. in two individuals in South Carolina. P.1 has been spotted in 11 countries. The first U.S. case was announced on Jan. 25 in a traveler returning to Minnesota from Brazil.
Before unpacking the implications of these variants for the pandemic, it’s important to emphasize that mutation itself is not surprising, as viruses mutate relatively quickly. These changes come about randomly as the pathogen replicates, making inevitable errors as the genome is copied again and again.
Variants appear all the time. “It’s very normal,” said Emma Hodcroft, a postdoctoral researcher at the University of Bern in Switzerland and a co-developer of the virus-tracking site Nextstrain, in an email to SciCheck.
Most mutations or collections of mutations don’t alter the virus’s biology or how human immune systems respond, although genomic scientists can track the alterations to understand how the virus is spreading. But on occasion, those types of mutations can arise and persist in populations, particularly if there is a competitive advantage for the virus.
“What causes us to take notice is when we see changes in how the virus behaves,” Hodcroft said, “like that one variant is expanding faster than others or than we expect.”
Even then, that’s no guarantee that a variant poses any extra threat. Over the summer, for example, Hodcroft said one variant expanded its reach across Europe, but that was mostly due to loosened restrictions and increased travel. When variants do exhibit such behavior, however, it’s worth investigating.
As the Centers for Disease Control and Prevention explains, the kinds of changes that might matter for the pandemic include those that allow the virus to:
- spread more quickly;
- increase or decrease the severity of COVID-19;
- lead existing diagnostic tests or therapeutics to fail;
- enable the virus to evade immunity resulting from natural infection or a vaccine.
With at least two variants that appear to be more contagious, scientists say concern is justified, but that the game plan remains the same: Get vaccinated and double down on public health precautions.
“The most important thing about new variants is that they still need humans in order to spread,” Hodcroft said, “so we can prevent them through the techniques we know work: masks, hand washing, staying home as much as possible, avoiding crowded spaces, & being aware of aerosol transmission risks.”
Nicholas Davies, an epidemiologist and assistant professor of mathematical modeling at the London School of Hygiene and Tropical Medicine who is studying coronavirus variants, echoed that call.
“It doesn’t spread in a different way, it just spreads more efficiently,” he told us, which means sticking to the standard public health measures will still work to limit transmission.
The other piece is immunization. “That’s really the end game for this pandemic, is getting people vaccinated,” he said. “And the emergence of these new variants I think makes that more important than it’s ever been.”
In a Jan. 15 report, the CDC likewise warned that with the arrival of B.1.1.7 to American shores and its increased transmissibility, the variant “warrants universal and increased compliance with mitigation strategies, including distancing and masking,” and said “[h]igher vaccination coverage might need to be achieved to protect the public.”
Variant Emerged in U.K.
Of all the known SARS-CoV-2 variants, B.1.1.7 has garnered the most attention and study. It has an unusually high number of genetic changes and was first identified in southeastern England when public health officials were investigating a spike in COVID-19 cases in early December, with the earliest instances stemming from patient samples taken in September.
The variant began to quickly dominate in the region and also spread to other parts of the U.K., where it replaced other viral lineages. While it is not always easy to determine whether that type of pattern necessarily means a virus has evolved to become more contagious, Harvard epidemiologist Marc Lipsitch told us he believed there was now a consensus that B.1.1.7 is more transmissible, noting that “data from multiple places in the UK are compelling.”
The most direct evidence of an increase in transmissibility comes from contact tracing data, Davies said. Public Health England found that as of Dec. 20, 14.7% of those in contact with people infected with B.1.1.7 contracted COVID-19, compared with 11% for those not infected with the variant.
Researchers also have used modeling or other statistical techniques to estimate how much more infectious B.1.1.7 is. Davies’ group, for instance, pegged B.1.1.7 as 56% more infectious than preexisting versions of the virus in a preliminary, unpublished preprint released at the end of December.
Scientists at Imperial College London also released an unpublished report that estimated the variant increased the reproduction number, or how many people on average each person with COVID-19 infects, by 0.4 to 0.7.
Davies said that while it’s hard to pin down an exact estimate — the numbers vary based on the models — B.1.1.7 is likely somewhere between 30% and 70% more contagious.
Preliminary data from the National Health Service initially suggested that B.1.1.7 does not cause more severe COVID-19 compared with past versions of the virus, as there was no statistically significant difference in the proportion of people infected with the variant who were hospitalized or died within 28 days compared with those infected with other strains.
Subsequently, however, British authorities revealed on Jan. 22 that four analyses indicated there was a “realistic possibility” that B.1.1.7 could be more lethal, although they cautioned that this was based on limited data and was still uncertain.
Even if B.1.1.7 doesn’t cause more severe COVID-19 symptoms, experts caution that an increase in transmissibility can still lead to a large number of deaths. In fact, because of the exponential nature of viral spread, an increase in contagiousness can have a bigger effect than the same uptick in a virus’s virulence, or ability to harm a host.
Running the math on a hypothetical virus with similar characteristics to SARS-CoV-2 in a city with 10,000 infections, London School of Hygiene and Tropical Medicine mathematician and infectious disease researcher Adam Kucharski explained on Twitter that a variant that’s 50% more deadly would eventually kill 64 additional people after a month, but a variant that’s 50% more transmissible would claim an extra 849 lives.
Of B.1.1.7’s 23 mutations, 17 change the protein sequence and eight of these occur in the virus’s spike — the protein that sticks out from the surface and is used to enter human cells.
Specifically, B.1.1.7 has a mutation known as N501Y (the name refers to a change in the protein sequence at position 501 from the amino acid asparagine to tyrosine). This is of particular note because it occurs in the receptor binding domain — the spot on the spike that binds to the ACE2 receptor on human cells — and previous experiments suggest it enables the virus to bind to the human receptor more tightly. A study in mice also found that making this change allowed the animals to be more easily infected and to get sick.
Other mutations of interest include a short deletion that is predicted to alter the shape of the spike protein and another change near an enzyme-binding site that could affect how the virus enters cells.
While the mechanism for why B.1.1.7 is more contagious still needs to be studied, tighter binding to human cells — due to the N501Y mutation or perhaps in combination with other mutations — could account for the phenomenon.
“As you breathe in some virus, if the virus is more efficient at latching on to its target surface, you’re more likely to get an infection,” explained Shane Crotty, an infectious disease researcher who studies COVID-19 at the La Jolla Institute for Immunology, in an interview with the YouTube channel MedCram.
Crotty also pointed to preliminary work from a governmental lab in the U.K. indicating that people infected with B.1.1.7 had higher viral loads, or levels of the virus, in their noses than people harboring other strains.
“If that’s true, it would say that this U.K. variant has amassed a set of mutations that let it grow a lot better in nasal passages than the previous virus and that there’s literally just a lot more virus in people’s nose,” he said. “If there’s just more virus coming out of you when you’re breathing or sneezing or coughing, then obviously it’s going to be more likely to able to infect people near you.”
So far, B.1.1.7 remains rare in the U.S., and it does not explain the surge of COVID-19 cases and hospitalizations that began in the fall.
Duncan MacCannell, the chief science officer with the CDC’s Office of Advanced Molecular Detection, told the Washington Post on Jan. 11 that he estimated that only 0.5% of COVID-19 transmission in the country involves the variant.
But many scientists expect the proportion of COVID-19 cases due to the variant will rise.
Trevor Bedford, a computational biologist studying viral evolution at the Fred Hutchinson Cancer Research Center and co-developer of Nextstrain, said in a Jan. 7 interview with NPR that based on the timeframe observed in the U.K., he thought B.1.1.7 could become the dominant strain in the U.S. by March.
CDC modeling, shared in a Jan. 15 report from the agency, similarly concluded that B.1.1.7 could become the predominant variant in the month of March.
Variant Identified in South Africa
Compared with its U.K. counterpart, less is known about B.1.351, which was first observed in South Africa. In a preprint posted on Dec. 22, scientists noted that the variant quickly came to be the dominant virus in the country’s two most southern provinces and might be more transmissible.
Few research groups have attempted to quantify the variant’s possible increase in contagiousness, although one tentatively estimated it to be 50% more infectious, with a range between 20% and 113%.
According to the same unpublished report, the case fatality ratio did rise in the region as the variant took over, suggesting a possible effect on disease severity, but there is no firm evidence that B.1.351 is more deadly than ancestral viruses.
Davies, the London School of Hygiene and Tropical Medicine epidemiologist who also co-authored the preprint, explained that the proportion of people dying could have gone up for a variety of reasons unrelated to a change in viral virulence.
“When hospitals are under more pressure the standard of care that they’re able to provide tends to go down,” he said. “So it could be, for example, that because [the variant is] more transmissible, they’re seeing more cases, and they’re less able to treat the people coming in.”
B.1.351 harbors multiple mutations in its spike protein, three of which occur in the receptor binding domain. This includes N501Y — the key mutation in B.1.1.7 — and another one nearby, E484K.
E484K is especially noteworthy, as researchers have found that the mutation reduces the ability of antibodies collected from people who recovered from COVID-19 to neutralize the virus. This raises concerns that the variant could pose more of a risk to populations because it could be better at reinfecting people and vaccines might not work as well against the variant.
Most scientists, however, caution against assuming the worst. As Jesse Bloom, a researcher who studies viral evolution at the Fred Hutchinson Cancer Research Center whose lab performed the antibody experiments, explained on Twitter, there is no reason to think that all immunity would be lost or that existing vaccines would suddenly fail.
“I’m confident current vaccines will be useful for quite a while,” he said, noting that the E484K mutation only reduced the neutralization activity of the antibodies present in some people’s blood, and didn’t eliminate it for anyone.
“So we need to monitor these mutations, and be prepared to update vaccines eventually if needed,” he added. But, he said, less effective neutralizing antibodies, “while worrying,” are “not the same as complete elimination of all immunity.”
Indeed, Moderna announced on Jan. 25 that the antibodies collected from people immunized with its vaccine were still able to neutralize a virus with the full set of spike mutations present in the B.1.351 variant, but it took around six times more antibody to do so than for previous versions of the virus. The results have not yet been peer reviewed, but were posted in a preprint to bioRxiv in collaboration with researchers at the National Institutes of Health.
Although in theory the N501Y mutation, by virtue of being located where it is on the spike protein, might also be a concern for immune evasion, experiments thus far have not revealed any problems.
Bloom’s lab, for example, did not find that mutations in N501 strongly diminished the ability of any person’s antibodies to bind to the virus. A similar test on antibodies from 20 people vaccinated with the Pfizer/BioNTech vaccine also found no reduction in the ability of those antibodies to neutralize a virus with the N501Y mutation, according to an unpublished report conducted by scientists at the University of Texas in collaboration with Pfizer.
Public Health England also reported on Jan. 14 that antibodies from people infected with non-B.1.1.7 viruses still neutralized the variant, and vice-versa.
Other experiments from the vaccine makers likewise suggest B.1.1.7 is unlikely to pose a problem for the current shots. As detailed in a report published in the journal Science, Pfizer found that antibodies from people immunized with its vaccine could neutralize a virus with B.1.1.7’s full set of spike mutations almost as well as an unmutated virus. Moderna reported similar findings for its vaccine on Jan. 25.
The good news is that should any variant prove to be evading a vaccinated person’s immune response, the two COVID-19 vaccines with emergency authorization in the U.S. can be quickly modified. Both use messenger RNA to train the immune system to recognize SARS-CoV-2, which can be revised by swapping in a molecule with a slightly different sequence.
Recent Variant in Brazil
Relatively little is known about the P.1 lineage variant, which a group of scientists first named in a Jan. 12 post on a virology discussion forum. Similar to the situation in the U.K. and South Africa, the variant was identified following a surge of COVID-19 cases, this time in Manaus, Brazil.
Although P.1 arose independently, it shares several genetic changes with the other variants of concern, including N501Y and E484K.
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.
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