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'It could get significantly worse': Could even more dangerous variants follow delta?

The delta variant is one of the most virulent coronavirus variants that have emerged over the course of the pandemic. As it causes surges in Covid-19 cases around the world, many public health experts are concerned it could "morph into something more formidable."

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How coronavirus variants have mutated so far

When the coronavirus first began circulating, humans were a new host, which allowed it to easily pick up mutations, STAT News writes. These first mutations made the virus more transmissible, allowing it to spread beyond Wuhan, China, to other places all over the world.

Over time, as the coronavirus spread, it picked up more mutations, which led to the development of different variants of the original virus. "The longer the virus persists, the more opportunities it'll have to sample what makes it more fit," said Oliver Fregoso, a virologist at the University of California-Los Angeles.

For example, several independent research groups have found evidence suggesting variants can more easily arise in people with weak immune systems, The Atlantic reports. After being infected, some people with weak immune systems may have the virus in their bodies for months, which provides the virus time to mutate and eventually become strong enough to spread to other people.

In fact, scientists believe the alpha variant emerged from one immunocompromised individual who had a rare chronic Covid-19 infection, STAT News writes. In addition, The Atlantic reports that the alpha variant has "an unusual number of mutations," which may be a sign that it developed in one person.

But prolonged infections are not the only ways variants can develop. In contrast to the alpha variant, the delta variant has relatively few mutations, and it may have emerged from several brief infections that happened close together in one place instead.

The type of mutation a variant develops may also depend on what conditions were like where it emerged. For example, the beta and gamma variants have mutations that make them less recognizable to antibodies. They were first identified in South Africa and Brazil respectively, where a large part of the population may have already been infected by an older version of the virus.

The delta variant, on the other hand, was first identified in India, where Covid-19 cases surged later and fewer people have encountered the original virus. The delta variant's mutations increased its transmissibility, allowing it to beat other variants in the area before eventually spreading around the globe.

What future variants could develop?

"Delta is already a really strong competitor," Michal Tal, an immunologist at Stanford University, said. "It could get significantly worse."

According to The Atlantic, it is difficult to predict what variants might come after delta or what they will look like. In one situation, delta may continue to become more infectious, or it could be replaced by another super-infectious variant.

However, due to growing immunity among the global population, increased transmissibility will likely not be enough to sustain the coronavirus over time. As immunity increases, the virus will have to develop mutations that allow it to bypass immune protections instead.

"There's some sort of tipping point where immune evasion becomes a bigger fitness advantage than transmission," Stephen Goldstein, an evolutionary virologist at the University of Utah.

In the worst-case scenario, a variant could emerge that would "make it like the vaccines did not exist," Bill Hanage, an epidemiologist at the Harvard School of Public Health, said. However, Hanage said that "there is no such variant like that" now.

Moreover, it would be "extraordinarily difficult" for a variant like that to occur, according to The Atlantic. In fact, even the most evasive variants currently circulating have not been enough to "fully dup[e]" vaccinated immune systems.

While new variants could bypass some of the defenses provided by vaccines, the body's immune response should still be able to protect people from severe disease, STAT News writes.

"A virus just can't change a couple amino acids and completely evade the totality of the immune response," Angela Rasmussen, a virologist at the University of Saskatchewan's Vaccine and Infectious Disease Organization, said.

Separately, Florian Krammer of Mount Sinai's Icahn School of Medicine, said, "I don't think that we'll end up with variants that completely escape antibodies or vaccine-induced immunity." 

In addition, a preprint study in bioRxiv found that even if a variant emerged that could escape immune protection—a scenario that Paul Bieniasz, one of the study's authors, said is "extremely unlikely to happen suddenly"—a booster shot could raise people's antibody levels high enough to combat the evolved virus.

"Even if the virus acquires those resistance mutations, it's possible to generate an immune response that'll cope with that," Bieniasz added.

How to protect against future variants

According to The Atlantic, the most powerful tool is vaccination. Vaccines can not only be altered to accommodate new variants—and boosters administered to increase immune response—but they can also be proactive interventions that help prevent the development of future variants.

Vaccination can reduce the number of chances for the virus to evolve, by reducing the opportunity for infection as well as the duration and intensity of any infections that do occur. The virus will have less time to mutate if it doesn’t remain in a person's body for long, and any mutations will be less likely to be passed on.

"The pressure is there, but the opportunity is not," said Jeremy Kamil, a virologist at Louisiana State University Health Shreveport. "The virus has to replicate in order to mutate, but each virus doesn't get many lottery tickets in a vaccinated person who's infected."

In fact, a preprint study in medRxiv suggests that the coronavirus's mutation rate is lower in countries with high vaccination rates. But even highly vaccinated countries are struggling amid the spread of the highly contagious delta variant, which means that there will be more opportunities for the virus to mutate.

According to Jennifer Dien Bard, a clinical virologist at Children's Hospital Los Angeles, new variants will continue to emerge "until we get to the point where the virus is not allowed to replicate this often, or this quickly."

Ultimately, those who remain unvaccinated will, at some point, get infected, with a devastating cost to public health. Goldstein added, "There's no scenario we choose where we don't impose selective pressure on this virus. But are we going to do it while we prevent people from dying, or not?" (Joseph, STAT News, 8/20; Wu, The Atlantic, 8/24)







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