The Most Worrying Mutations in Five Emerging Coronavirus Variants

When the coronavirus SARS-CoV-2 burst upon the world last winter, scientists knew it was bad. But they also thought it was stable. Coronaviruses do not mutate as readily as the viruses that cause the flu, hepatitis or AIDS, for instance—thanks in part to a molecular “proofreading” system that SARS-CoV-2 and its kin use to prevent damaging genetic errors when replicating.

Researchers were only partly right. The virus is indeed bad—but it is not so stable after all. SARS-CoV-2 has been acquiring minor random mutations ever since it jumped from animals to humans. These mutations can take the form of single-letter typos in the viral genetic code or deletions or insertions of longer stretches. When they occur, most mutations either kill the virus or cause no change in its structure or behavior.

But in recent months, several new variants of the original virus (also called the wild type) have been spotted that appear to cause major changes in the way the pathogen acts, including alterations to its contagiousness. These viral versions have seemingly popped up in rapid succession in different geographical regions, such as the U.K., South Africa and Brazil, and in some cases have outcompeted the existing variants. Although improved surveillance and sequencing efforts might partly explain why these variants are appearing now, some repetition in their patterns suggest the mutations are not random.

“What we’re seeing is similar mutations arising in multiple places,” says Adam Lauring, a virologist at the University of Michigan. “That’s pretty suggestive that these mutations are doing something.”

Specifically, they appear to help the virus transmit more readily and evade the immune system. This month researchers reported, for the first time, that antibodies from individuals with COVID did not completely neutralize a variant first identified in South Africa. A few people who recovered from the disease also appear to have been reinfected with the mutant virus.

Thus far, vaccines made by Moderna and Pfizer seem to work against the new variants, although Moderna has begun developing a booster shot specific to new variants. Because these two vaccines are more than 90 percent effective, a slight drop in effectiveness would still make them worth using, experts say.

“I’m optimistic this won't compromise the [COVID vaccines], but obviously, it’s something we’ve got to watch closely,” Lauring says. In coming years, he adds, companies may need to retool these vaccines and administer updated versions, much in the same way that flu vaccines are revised each year. Most vaccines cause a much stronger immune reaction than a natural infection with a virus. And in clinical trials for its vaccine, Moderna found that the antibodies produced after vaccination may last longer than those naturally produced after SARS-CoV-2 infection.

Here are five of the most prominent variants, listed in the order that researchers first spotted them. This roster identifies where each variant was first seen and gives the technical name or names scientists use to identify it. (Naming variants has caused some confusion because different research teams employ different systems. This list uses one based on the ancestral lineage of each variant, but some variants still have more than one name). The entries also highlight important mutations in each variant—denoted by letters and numbers that indicate their position in the sequence of the viral genome—and describe what scientists know or suspect about what those changes do.

SPAIN

Names: 20A.EU1, B.1.177
Notable mutation: A222V

The 20A.EU1 variant, first identified in Spain, contains a mutation called A222V on the viral spike protein. The spike is a component of SARS-CoV-2 that binds to a receptor on human cells called ACE2, and this attachment helps the virus get inside those cells and infect them. The spike protein is also the part of the pathogen that is targeted by human antibodies when they fight back against the infection. In lab tests, human antibodies were slightly less effective at neutralizing viruses with the A222V mutation. Over the course of several months, the 20A.EU1 variant became the dominant one in Europe. Epidemiologists never saw any evidence that it was more transmissible than the original, however. Researchers believe that when Europe began lifting travel restrictions last summer, the variant that was dominant in Spain spread across the continent.

U.K.

Names: 20I/501Y.V1, VOC 202012/01, B.1.1.7
Notable mutation: N501Y

Scientists in the U.K. had been watching the B.1.1.7 variant for some time before announcing in December that it might be at least 50 percent more transmissible than the original form. That announcement was based on epidemiological data that showed the virus rapidly spreading throughout the nation. And it led to international travel bans and stronger lockdown measures in the U.K.

The B.1.1.7 variant contains 17 mutations, including several in the spike protein. One of them, N501Y, has been found to help the virus bind more tightly to the ACE2 cellular receptor. It is unclear, however, whether the variant’s enhanced contagiousness comes from N501Y alone or also involves some combination of other spike protein mutations.

Despite initial concerns, there has been no real evidence that the variant is more infectious in children than the original, says University of Cambridge microbiologist Sharon Peacock, who is executive director of the COVID-19 Genomics UK (COG-UK) Consortium, a group that analyzes genetic changes to the virus. Both Pfizer and Moderna believe that their COVID-19 vaccines will still work against B.1.1.7. Recent data from the U.K. hint that the variant may be more lethal than the original, but the analyses are preliminary.

B.1.1.7 does stand out because it accumulated so many mutations, apparently all at once. Lauring and others suspect that these mutations may have arisen within one immunocompromised patient who was infected for a long time because that person was unable to fight off the virus. It is likely that only a few of these changes gave the variant an evolutionary advantage and allowed it to quickly spread around the U.K., says Scott Weaver, a microbiologist at the University of Texas Medical Branch at Galveston. The others were simply along for the ride.

SOUTH AFRICA

Names: 20H/501Y.V2, B.1.351
Notable mutations: E484K, N501Y, K417N

The B.1.351 variant appeared around the same time as B.1.1.7, and it spread quickly in South Africa to become the dominant version in that country. Like its European counterpart, B.1.351 contains the N501Y mutation, although evidence seems to suggest the two variants arose independently. But scientists are more concerned about another mutation called E484K that appears in the South African version. The genetic change may help the virus evade the immune system and vaccines.

Using yeast cells, evolutionary and computational biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center in Seattle and his lab created a series of spike proteins with almost all of the more than 3,800 possible protein component changes that could be driven by genetic mutations. Then the scientists tested how well or poorly human antibodies bound to each altered spike. They found that E484K—as well as similar mutations at that particular spot in the protein—made it as much as 10 times more difficult for antibodies to bind to the spike in some people. Bloom’s lab also found that some antibody cocktails, such as one currently being tested by the drug and biotech companies Regeneron and Eli Lilly, may be less effective against mutations present in the B.1.351 variant.

Late this month researchers in South Africa released a preprint study (research that has not yet been peer-reviewed) showing that an antibody-containing serum from COVID patients was considerably less effective at neutralizing this variant. And in another preliminary preprint posted on January 26, scientists reported they put B.1.351 into serum taken from people who had been vaccinated with either the Pfizer or Moderna vaccine. They found antibodies in that serum showed reduced neutralizing activity against the mutant, compared with their activity against the original virus.

Antibodies in test tubes are not the same thing as vaccines in real people, however. Both vaccines produce so many antibodies that a drop in activity could still leave enough of them to neutralize the virus. The vaccines also stimulate other protective components of the immune system. Still, Moderna has begun work on a booster shot specific to new variants.

BRAZIL

Names: B.1.1.28, VOC202101/02, 20J/501Y.V3, P.1
Notable mutations: E484K, K417N/T, N501Y

Names: VUI202101/01, P.2
Notable mutation: E484K

In January researchers reported they had detected two new variants in Brazil, both descendants of a somewhat older common ancestor variant. Although they share mutations with other newly discovered versions, they appear to have arisen independently of those variants.

Of the two, researchers are currently more concerned about P.1. That variant contains more mutations than P.2 (though both have E484K), and it has already been seen in Japan and other countries. Although it is possible that P.1 accumulated its mutations in an immunocompromised individual, genetics researcher Emma Hodcroft of the University of Bern in Switzerland says that it might be more difficult to pinpoint the time and place when this variant first arose because Brazil does not sequence nearly as many viral samples as the U.K.

Hodcroft points out that both Brazil and South Africa had large COVID outbreaks in 2020. With so many infected people creating antibodies against the virus, a version that could evade the immune system and reinfect a person who had recovered might have a strong advantage and then become more widespread in a population.

VIRAL SPREAD AND CHANGE

Although the seemingly sudden emergence of several spike protein variants is reason for concern, researchers say there is no evidence that the virus has changed in a fundamental way that lets it mutate more rapidly. What is most likely, Lauring says, is that the sheer number of COVID cases worldwide is allowing the virus numerous opportunities to change a little bit. Each infected person is, essentially, a chance for SARS-CoV-2 to reinvent itself. “Some of it is evolution, but a lot of it is epidemiology,” Lauring says. Overall, “the virus is getting better at being a virus.”