A variant of SARS-CoV-2 called B.1.1.7 was first detected in the UK in late November 2020 and is gaining ground in the US and worldwide. Researchers estimate that B.1.1.7 is about 50% more transmissible than most versions of the virus that are circulating in the US—raising concerns that, if it is not contained in the US and around the world, the variant will become dominant and drive a spike in severe illness and death caused by COVID-19. A second highly transmissible strain, first identified in South Africa and dubbed B.1.351, also appears to be highly transmissible and has already been detected in several other countries.
Researchers around the world are monitoring the prevalence of the two strains. They are also investigating how the mutations that these strains carry affect SARS-CoV-2 function, as well as whether and how or if these mutations might change the efficacy of vaccines against the virus. Here’s a rundown of what we know so far.
How did researchers first identify the B.1.1.7 variant?
Public health researchers in the UK, which has a robust viral sequencing and surveillance system, noticed in December that a particular lineage of the virus was becoming alarmingly common in southeast England, raising concerns that it transmits from host to host more efficiently than other strains.
B.1.1.7 has 23 mutations, 8 of them in the spike protein, which the virus uses to enter host cells. What helped researchers detect the strain is that the variant affects the result for one widely used polymerase chain reaction (PCR) test for the virus. This test looks for three regions of the virus’s genome, including a sequence on the spike protein that’s deleted in the variant. The test still yields a positive SARS-CoV-2 test result for the variant because it detects the two other segments of the virus’s genome, but the third spot does not show up in the test result because of the deletion, says Winston Timp, an engineer at Johns Hopkins University leading the university’s SARS-CoV-2 sequencing efforts. That change doesn’t confirm that the sample is B.1.1.7, because other strains also have the mutation that causes the third spot to disappear. But it provides researchers with a quick screening tool. UK researchers coordinate with the country’s public health system to routinely sequence the full genome of many random samples of SARS-CoV-2 as part of the country’s pathogen surveillance effort. This effort, called the COVID-19 Genomics UK Consortium, is supported by an investment of £20 million ($27 million), and has sequenced approximately 10% of SARS-CoV-2 samples in the country. When the researchers noticed increasing numbers of PCR tests with the missing spot, they were able to go back to sequences from September and track the variant’s exponential spread in the southeast of the country.
The US, meanwhile, sequences virus samples more unevenly, says Pavitra Roychoudhury, a bioinformatician focusing on viral evolution at the University of Washington. Only about 1% of samples in the US have been sequenced, and often with long delays. Although some states have robust public health sequencing programs, others do not. “Given that there are so many outbreaks going on in parallel, what we need is more continued ongoing surveillance for genomic variants,” Roychoudhury says.
How do researchers know that this B 1.1.7 is more transmissible than other circulating strains?
Most evidence for estimating the variant’s transmissibility comes from epidemiological analysis. In December, UK government researchers reported that people infected with B.1.1.7 went on to infect 15% of their contacts, whereas people infected with other variants passed on the infection to just 10% of their contacts, suggesting a 50% increase in transmissibility. Additionally, some computer modeling data that have not yet undergone peer review suggest that a mutation called N501Y, which is present in the receptor-binding domain of the spike protein in both B.1.1.7 and in B.1.351, confers stronger binding between the virus and the receptor in cells that the virus targets to infect the host. There is also evidence, also not yet peer-reviewed, that people infected with B.1.1.7 often have higher viral loads—that is, more virus circulating in their blood.
The fact that both variants share the N501Y mutation “suggests that it’s favorable and that there is some pressure selecting for it,” Timp says. So far there’s no direct evidence from lab studies of the variants supporting an increase in transmissibility, but researchers are studying the issue, he says.
What’s surprising about these variants?
Different viruses have “an inherent clocklike mutation rate,” Roychoudhury says. RNA viruses like SARS-CoV-2 tend to accrue mutations quickly. But unlike other RNA viruses such as HIV or influenza, coronaviruses have a proofreading mechanism that corrects some errors during replication. Researchers were therefore surprised that B.1.1.7 seems to have acquired most of its mutations all at once. “It’s sort of like one long branch sticking out from a bush” that is the SARS-CoV-2 evolutionary tree, Timp says. B.1.351 similarly has an unexpectedly high number of mutations.
Researchers have speculated that these variants may have arisen in immunocompromised people who were infected with the virus for long periods. One report that is not yet peer-reviewed tracked the evolution of the virus in an immunocompromised person who was sick with COVID-19 for many months. The researchers found that after more than 2 months, the virus acquired several mutations, including one found in B.1.1.7.
Although it’s a plausible explanation, “we don’t really have any smoking-gun data to support it,” Adam Lauring, a microbiologist studying viral evolution at the University of Michigan, says.
How prevalent is B.1.1.7 in the US and worldwide, and what are the chief concerns with its spread?
B.1.1.7 was first detected in the US Dec. 29in a man from Colorado. As of Jan. 11, the variant has been reported in eight US states in a total of 63 people, according to the US Centers for Disease Control and Prevention. But the fact that “we have a very primitive system for surveillance in this country means that it’s probably more widespread than we think,” Harvard University epidemiologist Marc Lipsitch said in a media briefing Jan. 5. Worldwide, 47 countries have reported B.1.1.7 as of Jan. 10.
The spread is concerning, experts say. “If we don’t act, and if [B.1.1.7] does have the increased transmissibility that it seems to, then I would expect it to become the dominant strain,” Timp says. So far there’s no evidence that B.1.1.7 increases the severity of disease. And there’s also no solid evidence that the variant spreads more widely in children. Although a UK report in December suggested this possibility because of the numbers of infections, researchers now think those numbers could be explained by other factors, Timp says, such as an overall increase in transmissibility.
Regardless, greater numbers of infections will mean greater numbers of severe cases and deaths. People will need to double down on containment efforts to try to keep the virus in check, Lipsitch said.
How does the emergence of B.1.1.7 and other variants affect prospects for vaccination?
The data available to date—many in preprint manuscripts that have not yet been peer-reviewed—suggest that antibodies produced in response to a vaccine should hobble B.1.1.7. The picture is murkier for B.1.351.
Most efforts to address this question have focused on mutations in the spike protein—which make up 8 of the 23 mutations in B.1.1.7—because the protein is so important to the virus’s ability to enter host cells and because it is a key vaccine target. But other mutations may also affect the virus’s transmissibility and its ability to cause severe disease, Timp says. “People are trying to figure out what these mutations are doing,” he says.
In a preprint posted Jan. 4, researchers systematically mutated each of the 201 amino acids in the spike protein’s receptor-binding domain and examined how well antibodies in serum from people who had recovered from COVID-19 bound to and neutralized the resulting virus. If any of the mutations disrupted this neutralization, it would indicate that the mutation might diminish the efficacy of vaccines that target the spike protein, as the two approved in the US (one manufactured by Pfizer and the other by Moderna) do.
The team found that a few of the mutations reduced the serum antibodies’ ability to bind to and neutralize the virus. The most potent of these was a mutation called E484K, which is present in B.1.351 but not in B.1.1.7. Meanwhile, N501Y, which is present in both B.1.1.7 and B.1.351 and thought to contribute to the increased transmissibility of these variants, did not affect antibody response.
Allison Greaney, a graduate student in Jesse Bloom’s lab at the Fred Hutchinson Cancer Research Center who worked on the study, notes that she and her colleagues looked at one mutation at a time but that a combination of mutations may have different effects, so how exactly these studies apply to the two emerging variants isn’t clear. Still, the results suggest that mutations in the spike protein don’t disable the vaccine. Even the E484K mutation does not knock out antibody response completely, she says.
A preprint posted Jan. 7 by Pfizer researchers directly tested the effect of the N501Y mutation on the vaccine and reported that it did not diminish the Pfizer vaccine’s efficacy. Tests on how other mutations affect antibodies produced by the vaccines are ongoing.
Should the presence of B.1.1.7 and B.1.351 and the possibility that other variants could emerge and spread—change how we manage the pandemic?
In many ways, no. The same strategies—practicing social distancing, staying at home, and wearing masks—are still required. In fact, they are more important than ever, despite the fact that many regions of the US have been lax in enforcing them. Widespread vaccination is also crucial; the potentially increased transmissibility of B.1.1.7 means that more people will need to be vaccinated for the public to reach herd immunity—the point at which enough people have achieved immunity to largely stop transmission, Lipsitch said in the media briefing. He also proposed focusing contact-tracing efforts on the new variant as a further effort to limit its spread. “Anything we can do to delay the spread of this new variant virus will make control [of the pandemic] easier,” Lipsitch said.
In the longer term, Timp says, the US will need to fund the infrastructure to allow the US to conduct routine extensive viral sequencing—not just for SARS-CoV-2 but for other pathogens too. “Public health labs in different states should have this capability, and we should make sure our tax dollars in the US go to that,” he says.
On Jan. 19, 2021, this story was updated to clarify the description of work published in a Jan. 4, 2021, preprint. The researchers mutated each of the the protein’s 201 amino acids, not each of its 4,000 nucleotides. Also, the team examined how antibodies bound to and neutralized the resulting viruses, not just how well they neutralized the viruses.