Arizona scientists said it’s likely that the so-called U.K. variant of the new coronavirus is already here and while it’s thought to be more contagious, they are more worried about a different variant first detected in South Africa.
Early data suggest the South Africa variant could affect vaccine effectiveness and increase the chance of reinfection.
More data is needed on the South Africa variant, but Arizona researchers say the state is not adequately monitoring for new strains and mutations of the virus, and needs to intensify its efforts.
Arizona State University suspects that several of its COVID-19 saliva test samples could be the U.K. variant, so named because it was first identified in the United Kingdom. It is also known as B.1.1.7.
The university is awaiting confirmation through sample sequencing, but at best, is playing catch-up to the virus. The samples being checked now were collected weeks ago, in late December.
Sample sequencing allows scientists to spot novel mutations in the virus or new strains.
Scientists have urged the state to implement real-time sequencing of all COVID-19 samples, instead of only sequencing a handful or waiting weeks after samples are collected.
“All we have to do is to make sure that we are one step ahead,” said Arizona State University virologist Efrem Lim. “If we start seeing these mutations, we can quickly figure out does it matter or not?”
In the U.K. and South Africa variants, two separate mutations and one shared mutation seem to matter most right now: the E484K mutation, the 69-70 deletion mutation and the shared the N501Y mutation.
Spike mutations cause concern
The virus seems to mutate every two weeks, according to past research, which is a relatively slow rate. But every time it jumps into a new host, it has another chance to mutate.
“Most mutations don’t really have a consequence or effect on the virus. But in general, there are three things that we care about for the virus mutations: one is whether it affects transmission,” Lim said.
Both the U.K. variant and the South Africa variant have a shared mutation widely thought to make them more contagious.
The second thing scientists care about is whether mutations affect antibody responses, Lim said, and the third thing is their effects on testing capabilities.
Mutations inside the virus’s genetic code for the spike protein could affect these three areas because vaccines and COVID-19 tests target this spike. That means a change in the spike could alter vaccine and test effectiveness.
The virus uses the spike to enter and infect cells, so any change to the spike could better enable virus to get into cells and spread throughout the body.
South Africa variant: antibodies thwarted
A lot of attention has been placed on the U.K. variant because it may be more contagious, but Lim said the South Africa variant, otherwise known as the 501Y.V2 variant or B.1.351, is more of a concern because of a unique mutation called the E484K mutation.
The E484K mutation is located in the spike of the virus and could make antibodies less effective, possibly hurting vaccination efforts.
One study from Seattle showed that this mutation caused the neutralizing effects of antibodies to decrease by tenfold. The study has not undergone peer-review.
In the experiment, scientists tested serum from recovered COVID-19 individuals, which usually contains antibodies that neutralize the virus. Further tests are still needed.
“We don’t know … whether vaccinated people could still be protected even if the antibodies are ten times weaker at recognizing this virus mutation,” Lim explained.
The next step, he said, will be testing serum from vaccinated people against the mutation.
While Pfizer has already tested its vaccine against one mutation found in both the U.K. and South Africa variant with positive results, the company has not yet published data on its effectiveness against the E484K mutation.
Jerica Pitts, Pfizer’s director of global media relations, said the company is working to obtain vaccine data on the “full range of mutations in the spike proteins of the U.K. and South African variants,” and will share those results once obtained.
A case report from Brazil found the E484K mutation was associated with a case of COVID-19 reinfection, which worries some scientists.
Despite the concerns, David Engelthaler, director of the Translational Genomics Research Institute’s infectious disease division in Flagstaff does not believe this mutation will fully stop the vaccine from working.
“We don’t think the virus is going to evade the vaccine,” he said.
Instead of stopping all antibodies, Engelthaler believes this mutation will only affect some, depending on where they target the spike. The mutation only targets one portion of the spike, so it will only affect antibodies that target that section.
“There are many, many different types of antibodies, so those will still work,” Engelthaler said. “It’s most likely that for people who are vaccinated and people who have had previous infections, the vast majority of them would be able to ward off an infection by this particular strain at this point.”
Eventually, such mutations will erode the vaccine’s effectiveness, according to Northern Arizona University microbiologist Paul Keim.
“Vaccine busters is what we’re all afraid of,” he said. “These variants don’t look like the vaccine busters to me.”
This mutation will likely affect some vaccines more than others, according to Lim.
Even if this mutation dampens vaccines, as long as they meet the government’s minimum threshold of being 50% effective, Keim expects vaccination efforts to continue.
Reduced effectiveness will allow unaffected strains to continue to circulate. This, combined with the wide COVID-19 spread across the globe means that vaccines could need to be modified and re-administered in the future, according to Keim.
“I believe that within a year we may be looking at new vaccines to counter new strains,” Keim said. “Unfortunately, this new variant I think is a harbinger of what we’re seeing in influenza already.”
He suspects that, just like flu shots, new COVID-19 vaccine shots will be needed on a yearly or semi-regular basis.
The good news is that mRNA vaccines, like Moderna’s and Pfizer’s, should be easy to quickly modify due to their flexible technology, Keim said. It’s unclear what additional testing will be required for updated vaccines, and whether regulations would slow vaccine response to new virus strains.
A more contagious mutation
So far, the South Africa variant of the virus does not seem to have spread as widely as the U.K. variant. The South Africa variant has been detected in 10 countries outside of South Africa, according to global research data and has not yet been detected in the United States. By contrast, the same database reports the U.K. variant in 29 other countries, including the United States.
One possible reason is because the South Africa variant is newer. Both variants share a mutation known as the N501Y mutation, which is widely believed to make them more contagious.
“This virus is evolving and one of the ways that it evolves is to transmit more efficiently,” Keim said. “This isn’t the first time we’ve seen this.”
The N501Y mutation reminds both Keim and Engelthaler of the D614G mutation, which spread across Arizona last spring and quickly became the dominant strain around the world.
Though the increased contagiousness of this strain was initially debated by scientists, multiple studies have since concluded that it made the virus spread more easily. One such study from the U.K. relied on the largest national database of coronavirus genome sequences in the world and showed that the mutation was associated with a higher viral load.
That mutation, combined with the new N501Y mutation, means that stopping the spread of COVID-19 may get increasingly difficult.
“We supercharged an already highly-charged virus and now it is spreading very, very quickly,” Engelthaler said.
The N501Y mutation occurs on a part of the spike responsible for physically attaching to the ACE-2 receptor on human cells, just like a lock and a key.
Because of its location, the mutation likely affects how easily the virus can enter cells and spread to new hosts. The fact that dominant strains in both the U.K. and South Africa have this mutation suggests it is responsible for increased spread, according to Engelthaler.
One study from the U.K. estimates that its variant with this mutation is 56% more contagious than prior strains. Researchers predicted that the likelihood of increased transmission would lead to higher levels of COVID-19 deaths and hospitalizations in 2021 than seen in 2020.
Researchers did not find any evidence that this variant was more or less severe than past variants. The study has not undergone peer-review.
Whether the N501Y mutation actually causes increased transmission is still largely speculation, Lim said. He hasn’t yet seen strong data to support this conclusion and said its spread could have been caused by other factors.
Even if the mutation does cause increased spread, case numbers are so high right now that Lim believes a change in the virus’s transmissibility is not likely to have a big effect. Because infected individuals are probably already spewing out millions of particles of the virus, an increase in a virus’s transmissibility would need to be dramatic to be noticeable, he said.
Keim still believes an increase in the novel coronavirus’s ability to spread is important.
“It really argues that people have to take social distancing and masks seriously because this virus will be able to transmit more readily and that makes those types of public health actions even more critical,” he said.
The more a virus can spread from one host to the next, the greater opportunities it has to mutate, he added, and more mutations could make the virus harder to fight.
Lim argued that scientists should be more concerned about any mutations that affect COVID-19 testing or vaccine efforts. So far, the N501Y mutation doesn’t seem to have any impact on vaccines, according to an announcement from Pfizer last Friday. Pfizer tested serum from 20 participants who received the vaccine and found antibodies in the serum worked just as well against variants of the virus with the N501Y mutation.
The study has not been peer-reviewed.
U.K. variant affects testing
In the case of the U.K. variant, another mutation known as the 69-70 deletion has affected COVID-19 tests by making one part ineffective. The mutation is named for the deletion of the 69th and 70th amino acids in the genetic code for the spike protein. Amino acids are the building blocks of life that create different proteins.
Many COVID-19 tests look for the presence of the spike gene, but this mutation means tests can no longer detect it. The Food and Drug Administration issued a warning last Friday that the U.K. variant could cause false-negative results in tests, particularly for those that rely on detection of only one region of the virus’s genetic code.
But the agency said the risk that the mutation will affect overall testing accuracy is low.
Most tests also look for one or two other genes in the virus outside of the spike, providing a fail-safe to ensure that the overall test results are still accurate, even if parts stop working.
That’s what led to unusual results in ASU’s saliva tests, where the presence of two virus genes was detected, but not the presence of the spike gene. It’s likely that some of these unusual tests will end up being samples of the U.K. variant — but not all of them.
“That deletion doesn’t only occur in the U.K. strain,” Engelthaler said. “So when we see that deletion … it doesn’t necessarily mean that the U.K. strain is here.”
Some strains circulating in the U.S. southwest have the 69-70 deletion mutation but aren’t the U.K. variant, he said, which is why sequencing is needed.
Even if the variant hasn’t yet reached Arizona, it has spread to neighboring states like California, so scientists believe it’s only a matter of time.
ASU should have confirmation within days. In the meantime, Lim and other ASU researchers are developing a new test to determine whether a result that doesn’t detect the spike gene is a false-negative.
‘It’s very embarrassing’
It’s not surprising to Engelthaler that new mutations and variants are popping up to change the flavor of the novel coronavirus, but he believes it’s critical to be aware of these changes.
To do that, the state needs to increase its sequencing capabilities.
The Arizona COVID-19 Genomics Union, which was formed to analyze and track different strains of the virus, has not sequenced many samples in the past few months, according to Keim, who is the group’s co-founder and director.
“It’s very embarrassing,” Keim said. “We can all sequence this virus, and we have been, but frankly, there hasn’t been the funding to do it.”
The low focus on sequencing is a national trend, according to Keim, who pointed out that the U.S. has not sequenced as many samples as the U.K. One of the reasons the U.K. was able to spot its variant was due to better genetic surveillance, he said.
“You can’t see what’s happening if you don’t look,” Keim said.
Since November, the Arizona Department of Health Services has sequenced 133 samples, according to ADHS spokesperson Holly Poynter. The state has also been providing samples to the Centers for Disease Control and to TGen, which is part of the genomics union.
But TGen does not have any direct funding to sequence the samples, according to Engelthaler. As a result, he said the state and TGen have been sequencing samples on a much more reactive basis, rather than sequencing in real time.
“I want us to be on a much more proactive basis and sequencing everything,” he said. “So we can see when aberrations happen and when new strains come into the state.”
TGen has the expertise and capacity to do more sequencing with more funding, Engelthaler said. And Lim said ASU has the capacity to sequence samples in real time if it receives more support from the state, which he said is now starting to happen.
“We are anticipating getting additional funding that will allow us to ramp up some of those activities with TGen and our university partners so that we can do even more sequencing,” state health director Cara Christ said during a news briefing Friday.
Engelthaler wants to see sequencing become an integrated part of the state’s overall COVID-19 health care response strategy for the future. That would allow the state to respond to new mutations and their effects and figure out the cause of re-infections.
“What we’re seeing now is a really glaring warning that we need to have eyes on the genome of this virus much more closely than we have,” he said.
Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environment. Send her tips, story ideas, or dog memes at email@example.com and follow her on Twitter @amandamomorris for the latest bioscience updates.
Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.
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