Virus Variants: How Mutations Could Shape US Vaccine Policy

Increasing scientific evidence about coronavirus variants bring into focus the science behind virus mutation, and why some researchers argue for changing U.S. vaccine policy. 

This figure from a study by S. Cobey shows potential vaccine-induced evolution. In (a), vaccination increases the transmission advantage of an escape variant compared with the wild type. The (b) image shows how the variant not spreading as readily because residual immune protection from vaccination has slowed transmission of the variant. The (c) graph shows how ‘intermediate’ immune pressure could in theory maximize the rate of adaptation within hosts. (Image via Courthouse News)

(CN) — As people around the world have had to adapt their lives to the presence of Covid-19, the virus causing the illness, too, has been morphing to make the most of its situation. 

Mutations that give way to emerging coronavirus variants remain a key factor in the race to vaccinate all American adults and curb the pandemic. Our existing vaccines seem to neutralize the most prominent variant in the United States, but not all virus mutations work the same way, opening up the possibility of a vaccine-resistant virus showing up in the future. 

Researchers agree that widespread vaccination — with continued mask-wearing and social distancing along the way — is vital to winning the race. What’s less clear at this point is how policy should reflect the ever-changing science on coronavirus variants, including how the science behind different variants can influence its spread. 

A snapshot of the latest science, and still-developing matters of policy, offers the hope of vaccination progress, while making clear that unanswered questions will ultimately decide the pandemic’s future. 

Science Behind Mutations  

Like all viruses, SARS-CoV-2 is able to replicate only inside a host organism. So the virus’s ultimate goal, its means to survive, is to spread as efficiently as possible. 

To achieve increased transmissibility, viruses mutate constantly. When a beneficial mutation appears in a virus’s genes, it’s likely to take over as the dominant version. 

But mutations can arise in different parts of the genome, and the various ways in which a virus becomes more transmissible can change what a variant means for human health. 

In the United States, for example, officials from the Centers of Disease Control and Prevention reported last week that the country’s most prominent variant — B.1.1.7, which originated in the United Kingdom — accounts for more than a quarter of U.S. cases and was the predominant strain in at least five regions. 

That doesn’t come as a surprise: The CDC had predicted a takeover of the strain known to be 50- to 70% more transmissible than what is known as the “wild type,” SARS-CoV-2.

Stephen Kissler, a postdoctoral researcher studying immunology and infectious diseases at Harvard T.H. Chan School of Public Health, explained how the variant spreads more easily on a “per-contact basis.”

“That probably has something to do with the way the virus interacts with our body’s cells,” Kissler said: It’s just easier for it to invade. 

But the P.1 variant, first identified in four travelers from Brazil during routine airport screening in Tokyo, uses a different strategy. 

The Brazilian variant may not be more infectious in general, Kissler said, but it “really thrives in places where we’ve already seen a lot of infections.” 

“Where previous immunity would keep other types of variants out, the P.1 can spread more easily because it gets around the immune system,” he explained. 

Viruses can also evolve to cause more severe illness. That’s not necessarily advantageous to a virus, which cannot spread if it kills its host. 

“But sometimes the same mutations that cause increased transmissibility, like better binding to our body’s cells, can create some more severe clinical manifestations, just sort of as a byproduct,” Kissler said. “And so that’s something that we have to watch very closely as well.” 

When SARS-CoV-2 enters the body, it binds to receptors in the lung cells to gain access to the rest of the body, “hijacking our cellular machinery.” Binding more tightly, Kissler said, not only helps the virus spread — but can also infect more cells within one person, worsening the virus’ effect. 

“When a virus infects our body’s cells, it causes quite a bit of damage, actually,” Kissler said. “It infects the cells, and ultimately ends up sort of exploding them, so that it can replicate.” 

That can contribute to more inflammation, which can cause more severe illness in some patients. 

While researchers are learning more about variants by the day, health officials are looking at adapting vaccination policy accordingly. 

Policy Surrounding Variants 

The CDC tracks variants, studying their genomes and analyzing the potential threat to health presented by each strain. 

As of now, the U.K. variant accounts for most variant cases, followed by the variants from South Africa and Brazil.

Categorizing the different virus spinoffs into “variants of interest” and “variants of concern,” the CDC signals which strains may be the most important ones to watch. But officials are still working out specific parameters for what makes a variant concerning. 

For instance, a variant from New York, B.1.5.2.6, is not yet classified as a concern. That does not mean it’s less of a priority, said Dr. Rochelle Walensky, director of the CDC, during a press briefing last week. 

“Rather, it means that we are still working to understand the variant, gather data on it, and determine its impact on medical therapies, disease severity, and transmissibility,” Walensky said Friday. “As we are better able to characterize the variance, its classification may change based on those findings.” 

A third category, known as “variant of high consequence,” is empty for now. A strain would be placed in that group if it is significantly vaccine-resistant, or causes much more serious illness than the wild type virus. 

Harvard’s Kissler explained that classifying variants happens by consensus among epidemiologists, public health experts and other scientists. There’s reason not to rush into developing criteria.

“We don’t yet know what are all the strategies that SARS-CoV-2 has it its arsenal,” Kissler said.

“We don’t want to get in a situation where we’ve developed a whole set of criteria, and the virus finds some new way of becoming concerning — but it doesn’t match up with our definitions — and we could end up missing it, just because we’re not looking for the right things.”

As researchers gain more data about variants, the information may also lend way to new policies for managing Covid-19. 

Some researchers argue that combating the pandemic is most effective when the maximum number of people are vaccinated, even if they only receive one shot of Pfizer or Moderna, authorized to be used as two-dose vaccines. 

Real-world CDC data shows that the two vaccines are 80% effective at preventing illness from Covid-19 with just one dose. 

Making the case for a single-dose strategy, a team of researchers published a recent perspective in Nature Reviews Immunobiology. The scientists addressed concerns that giving people one dose of vaccine could create opportunities for more variants to emerge that “escape” the neutralizing effect of coronavirus vaccines. 

That notion is backed up by research: In a separate study in Nature Medicine, certain faster-spreading variants, like the one from South Africa, “acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels.”

But the authors of the perspective paper say that the strongest chance of vaccine-resistant mutations occurring occurs during transmission. Vaccine-resistant variants “are likely to be transmitted more slowly than their ancestors were in unvaccinated populations,” the perspective authors write, “resulting in lower prevalence and incidence.”

“We argue above that dose-sparing regimens will not necessarily increase the risk of vaccine escape and might even lower it,” the researchers concluded. 

Dr. Stephen Bezruchka, an emergency physician and professor at the University of Washington, agrees with implementing a single-dose strategy — at least, short of other policy efforts that he said would be even more effective. 

Bezruchka said that, to best address the pandemic’s toll, the U.S. government should support people financially, pointing to high-income countries that furloughed workers last year with full pay, allowing more people to stay home. 

“I think a single-dose strategy to cover more people would be the right thing to do, if we’re not going to quarantine and support people,” Bezruchka said. 

A single dose of either Pfizer or Moderna “provides significant protection, and maybe enough for older people to not die of Covid,” he said, “but since it’s been a two-dose strategy, people feel that if you don’t get both doses, they’re missing out.” 

Dr. Anthony Fauci responded Monday to the idea of shifting to a two-dose strategy. 

“I don’t think there’s any right or wrong in this,” said Fauci, the country’s top infectious disease specialist. “There really are different approaches and different opinions.” 

A concern remains, Fauci said, about how long a single shot will remain effective. The 80% figure remains somewhat tenuous: “When you just leave it at one dose, the question is, ‘How long does it last?’” 

“There is some merit to the arguments that are made, and we certainly respect that,” Fauci continued. But at the United States’ current pace of vaccination, he said, things seem to be on the right track. 

“Literally, every day that goes by, we get closer and closer to where we want to be,” Fauci said. “For that reason, although we always continue to keep an open mind, we consider the route that we’re on now as the best route.” 

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