This story was published by STAT Dec. 21, 2020. You can find the original article here.
A variant of the coronavirus that emerged in the United Kingdom has forced London to shut down, led some countries to ban travel to and from the U.K., and set off a global manhunt to find out where else this version has arrived.
So what comes next?
Whenever a potentially significant viral variant emerges, experts want to study its effects on three key factors: how well it spreads, the disease it causes, and whether it can evade the protection people have against the pathogen, either because they’ve been infected already or are vaccinated against it.
Scientists have started to figure out the answer to the first: many increasingly think that this variant is more transmissible (though some are holding out for more evidence). And so far, it doesn’t seem to affect how sick people get.
As for immunity, experts are racing to answer that question and to ensure that the vaccines that are just reaching people are maintaining their effectiveness.
“It’s obviously associated with a lot of uncertainty at this point,” said Kristian Andersen, an infectious disease expert at Scripps Research Institute.
Is immunity intact?
As of now, there is no evidence that the virus has changed enough to get around existing immune protection. But experts say it’s crucial to confirm that because the variant has a number and array of mutations unlike other versions of the virus that have popped up throughout the pandemic.
“We shouldn’t just trust our priors that would be like, ‘No, the virus wouldn’t evolve this immune evasion,’” Andersen told STAT on Dec. 21. The constellation of changes this variant has “is really unusual,” he said.
Andersen added that he wasn’t predicting there would necessarily be some impact on the effectiveness of vaccines, but stressed that the studies, which are already underway in the U.K., can address that. The studies involve pulling antibodies from the blood of people who have either recovered from COVID-19 or been immunized and, in lab experiments, testing whether they still neutralize the variant.
Coronaviruses evolve more slowly than viruses like flu, but they do pick up mutations as they spread. SARS-CoV-2 has been adding one or two changes a month to its RNA genome since it emerged late last year in China, and different versions of the virus have been continuously circulating throughout the course of the pandemic.
But this variant, referred to as B.1.1.7 or VUI-202012/01, showed up with at least 17 mutations, according to one genetic analysis. Some are in the stretch of the genome with the instructions for the virus’ spike protein, which binds to human cells and enables the virus to infect them. The leading vaccines were designed to teach the immune system to make antibodies that can recognize and block the spike proteins, so it’s possible that changes to the spike could alter how well the vaccines work.
The same could occur with antibodies generated by an initial case of COVID-19, Wendy Barclay, the head of infectious diseases at Imperial College London, said at a briefing Dec. 21.
“There’s a chance that the antibodies that were made in the first infection won’t work as well against the new variant,” she said.
But Barclay stressed that the immune system has other components that contribute to protection, including fighters called T cells that can also recognize the virus. And she noted that vaccines elicit antibodies that can home in on different parts of the spike protein and that take different approaches to fighting off the virus, so even if some lost their ability to target the spike, the vaccines have other ways to block the virus. It would be unlikely that these changes in the variant could overcome all those layers.
Plus, if the virus were to evolve to “escape” vaccines — now or at some point in the future — it most likely wouldn’t render the immunizations ineffective entirely; it would just make them less protective, and they would need to be updated. It’s possible, Barclay said, the vaccines could be “compromised to some extent, and that’s what we need to check out.”
Because the vast majority of the world remains susceptible to the virus, there hasn’t been much evolutionary pressure on the virus to adapt, though that will change as greater proportions of the population get vaccinated. But in this case, experts think B.1.1.7 didn’t evolve through the normal pattern of slowly incorporating mutations into its genome as it copied itself as it spread.
Instead, they say it’s possible that an immunocompromised person who had a rare, chronic case of COVID-19 — whose long-lasting infection would have let the virus replicate for weeks or longer, building up mutations rapidly — could be the source of the new variant that has since spread to others.
Does it make people sicker?
Researchers are also investigating whether B.1.1.7 has any impact — for good or bad — on how sick it makes people, though so far the mutations only seem to have affected transmissibility, not pathogenicity (how the virus causes disease). Experts in the U.K. are reviewing the rates at which people with the variant are hospitalized and how long they stay, as well as deaths.
“It’s early days, so as people know, both hospital admissions and mortality are lagging indicators, usually take two to four weeks to see,” said Susan Hopkins, an epidemiologist at Public Health England. “I think we will be very cautious until we’ve had enough time to be able to make accurate assessments.”
Does it spread more easily?
All viruses mutate, and researchers have been looking out for potentially concerning SARS-2 variants for months. Already, one variant, known as D614G, helped increase the efficiency with which the virus spreads, most researchers agree. But other mutations that have raised alarms at times have turned out to be duds. Mutations occur all the time, and they can help the virus spread or sicken, or detract from that; many don’t have any effect at all. Some forms of the virus emerge and then disappear.
British researchers and public officials have said B.1.1.7 is more transmissible than other versions of the coronavirus — with estimates ranging from 50% to 70% more infectious.
But some scientists still want more evidence. It’s possible, for example, that a variant can look more contagious if it just happens to gain a toehold in an area first so it has the most room to run, or is the beneficiary of a couple pivotal superspreading events.
But multiple research teams have arrived at the same finding that B.1.1.7 is spreading more efficiently than other strains, based on epidemiological and genetic analyses.
“We now have high confidence that this variant does have a transmission advantage over other virus variants that are currently in the U.K.,” Peter Horby, an infectious disease expert at the University of Oxford, said on Dec. 21, upgrading his assessment from last week of “moderate” confidence. The variant is continuing to overtake other forms of SARS-2 in the country, scientists said.
There are various estimates of what that increase in transmission means, but researchers say the new variant could have increased the reproduction number — a figure known as R-naught, which is the average of how many people one person will infect — from 1.1 to 1.5. That is a big difference: with the former, 10 infected people on average would lead to 11 new infections, but with the latter, those 10 people would cause 15 new infections — a difference that would balloon from there as those secondary cases caused new infections themselves. R-naught can be lowered with interventions like masking and physical distancing. (Epidemics will grow if the figure is above 1, and shrink if it’s brought below 1.)
Experts aren’t sure yet what about B.1.1.7 appears to help it spread more easily. They’ve noticed that people with this version tend to have higher levels of virus in their upper airways than other people with COVID-19, so it’s possible more virus is being “shed.” Perhaps people are infectious sooner after they become infected themselves. One of the mutations, called N501Y, has also been shown to help the virus latch on better to the receptor it uses to infect cells, called ACE2. Another mutation affects what’s known as the virus’ furin cleavage site, which helps the virus enter cells as it attaches to them. These differences provide what Barclay called “biological plausibility” for the variant being a better spreader.
Indeed, researchers reported Dec. 21 that a separate variant spotted in South Africa that shares at least one mutation with the U.K. strain — N501Y — also has higher transmission rates.
British researchers also raised another point of concern about the new variant: it might be able to infect children at higher rates than other versions.
One of the saving graces of the pandemic is that SARS-2 has not been infecting children at the rates of adults (and has generally not made them nearly as sick). A hypothesis for this is that kids don’t have as many ACE2 receptors on their cells compared to adults.
But in the U.K., epidemiologists are finding that more infections among children are caused by the new variant compared to other versions. They’re trying to determine the significance of the pattern, but it’s possible that if the variant is better at latching onto ACE2 than other strains, it doesn’t need as many of the receptors to establish an infection.
“If the virus is having an easier time of binding and entering cells, then that would put children on a more level playing field,” Barclay said. “It sort of overcomes one of those barriers that the virus was meeting before.”
Already, at least one case of B.1.1.7 has been confirmed each in the Netherlands, Denmark, Italy, Iceland, and Australia. But experts have noted it’s the places that sequence the most viral samples from people who are infected that are reporting the variant. In other words, if countries look for it, they may find it.
“It is very likely that it emerged here,” Hopkins said, referring to the U.K. “However, it is very likely that it’s also in other countries, because there’s been transport back and forth between many European countries for the last three months.” (The British researchers first noticed the apparent transmission advantage of B.1.1.7 this month, but after that, they looked back through sequencing data and found that the variant first appeared in September.)
One country that does not have a coordinated sequencing system is the United States. Some research institutions have been studying genetic data and submitting them to a national database, but there is not a federal effort to ensure that viral samples are being collected and sequenced from groups of patients in a way that’s representative of geography and demographics. As late as this summer, for example, there was no sequencing information from any patients in Pennsylvania in the database, one expert told STAT.
“There was a rather random assortment of sequences,” said Diane Griffin, a virologist at the Johns Hopkins Bloomberg School of Public Health, who chaired a committee for the National Academy of Sciences about genomic epidemiology for SARS-2
Despite the concern about the new variant, experts reiterated Dec. 21 that the same public health measures preached since the early days of the pandemic could still combat its spread. Mike Ryan, the head of the World Health Organization’s emergencies program, noted that the R-naught in certain places has far exceeded 1.5 at various times, and that the virus was still brought under control. “In some senses, it means we have to work harder,” Ryan said.
WHO officials also noted that reducing transmission cuts the possibility of dangerous variants emerging.
“The bottom line is that we need to suppress transmission of all SARS-CoV-2 viruses as quickly as we can,” said WHO Director-General Tedros Adhanom Ghebreyesus. “The more we allow it to spread, the more opportunity it has to change.”