Why this coronavirus mutation is not cause for alarm
There’s no solid evidence that the coronavirus has become more deadly or transmissible. Here’s why such fears arise with every epidemic.
Mutations sound scary. They’re a common theme in our collective fear of nuclear radiation or insidious cancers. In a pandemic when so much remains unknown, even the suggestion that the virus is changing for the worse, getting more infectious or more lethal, intensifies our anxiety.
Hence it was no surprise that the news was flooded with frightful headlines in early July, after a study published in Cell, a prestigious journal, claimed a mutant strain of the SARS-CoV-2 coronavirus had quietly taken over the world—possibly because it was more transmissible.
In early March, the study said, this mighty mutant had accounted for only 10 percent of specimens pulled from patients around the world. But by May, it had obtained global dominance, accounting for 78 percent. The researchers reported laboratory experiments suggesting that the mutation in question—a single change in the “spike” protein that studs the virus like a crown—could somehow improve the virus’s ability to get into human cells and reproduce.
There’s no doubt that viruses mutate; that’s why we need a new version of the flu vaccine every year. But there is considerable doubt among scientists about how significant this particular mutation is for the COVID-19 pandemic. The Cell paper suggests this mutation allows the coronavirus to better bind and more easily enter human cells.
"There is zero evidence for this," says Vincent Racaniello, a virologist at Columbia University, who has written about why the Cell paper does not provide evidence for increased human transmission with this SARS-CoV-2 mutant. For one, the Cell study conducted its lab experiments with a “pseudotyped” virus, meaning the researchers did not use the real SARS-CoV-2 virus. To show that the mutation increases transmissibility, you would need to observe how the actual mutant behaves in people.
“There is a huge gap between infectiousness in a lab and human transmission,” says Nathan Grubaugh, an epidemiologist and virologist at Yale University. In the real world, he explains a virus has to make its way into the lungs—past mucus and the immune cells that line the airway. Then it has to replicate itself, and survive in droplets that are released back into the air. The takeaway outlined by the Cell study is plausible, Grubaugh says, but “there are so many other variables.”
So, how concerned should we be about coronavirus mutations? National Geographic asked leading virologists and physicians.
What we know so far about the G614 mutation
The authors of the Cell study, led by biologist Bette Korber of Los Alamos National Laboratory in New Mexico, cut and pasted the coronavirus’s spike protein—either the mutant version, called G614, or the original—onto a completely unrelated germ called a lentivirus.
The resulting “pseudoviruses” are a safe and reproducible way to work with and compare different viral spikes, Korber explains.
The team then mixed these pseudoviruses in test tubes with different types of kidney cells. One batch was extracted 60 years ago from Vervet monkeys, while the others were picked from humans in 1973. These cells have also been immortalized, akin to the famous tale of Henrietta Lacks. This means they have been modified either naturally or artificially to live forever—unlike the cells found inside a human body. Likewise, the human cells used in Korber’s study were also genetically altered to be more easily infected by any virus carrying the spike protein.
In this artificial, lab-based scenario, the researchers found the mutated spike to be more infectious. Coupled with the fact that the G614 mutation had risen to dominance in a matter of months, it sounded like an already scary virus might be getting better at jumping from person to person. Media reports exploded.
But what do the results mean for people at this point?
“We have no idea,” Racaniello says. While pseudovirus experiments are common practice in virology, they’re a bit like putting tiger teeth into the mouth of a koala. The mutant koala's bite might hurt more, but the experiment doesn’t tell you much about the ferociousness of koala bears or tigers outside the lab.
Korber acknowledges the limitations of the experimental results: “We do not know” how they will translate into transmissibility in humans, she says, but “that is currently being explored in several laboratories.”
Meanwhile, there’s an alternative explanation for why the mutant virus was able to rip across the population and dominate the outbreak—one that has little do with the G614 mutation itself.
The founder effect
Viruses can mutate while they replicate—each cycle represents a roll of the genetic dice. Many of those mutations may confer no advantage but will nonetheless be passed along until they are common in the population. This is called the “founder effect.”
The G614 mutation was first spotted in China in January 2020—just as the novel coronavirus was hopping into Europe. That suggests its global dominance may be due simply to seeding the early days of Europe’s outbreak, which then precipitated its spread to much of the Western Hemisphere. Indeed, when the University College London Genetics Institute took this founder’s effect into account in a recent analysis of coronavirus genomes collected from 23,000 patients worldwide, it found no evidence for increased transmissibility of any current mutations in SARS-CoV-2, including G614.
Although Korber acknowledges the possibility of the founder effect, she thinks the sheer prevalence of G614 around the globe suggests that the mutation confers a fitness advantage—and in her view the evidence suggests that it is outcompeting its ancestral strain. “Almost every single time, out of the dozens and dozens of times when both forms were co-circulating in a region, the virus shifted to higher frequencies of the [G614] form,” she says.
But a separate group of researchers, called the COVID-19 Genomics UK consortium, is tracking the G614 mutation among British patients and has analyzed more than 30,000 viral genomes so far. While the G614 mutation “may possibly increase the rate of transmission between people, the difference we see is much less than the difference in cell infectivity measured in the laboratory,” Erik Volz, an epidemiologist at Imperial College London and member of the consortium, said in a statement.
The consortium also found no evidence that G614 is making coronavirus infections more severe or more lethal, a pattern that was also reported by Korber’s group and by scientists in Washington State.
Although it is theoretically possible that a virus will hit the genetic jackpot and morph into something far deadlier and easier to spread, mutations that result in “X-Men-type changes” are also extremely unlikely, says Tyler Starr, virologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington.
A far more likely outcome, says Kristian Andersen, an immunologist at Scripps Research at La Jolla, California is that “the virus will keep mutating and most of these won't do anything—some of them will be slightly detrimental to its fitness, some of them slightly beneficial, which is all expected.”
When should we worry about viral mutations?
To anyone who remembers the Ebola outbreak in 2014 in Africa, the current conversation about G614 has a familiar ring. At the time, some experts floated the terrifying possibility that the Ebola virus, which killed roughly 50 percent of its victims but was transmitted only through bodily fluids, could morph into an airborne disease.
Early research three months into the outbreak showed the Ebola virus had acquired mutations similar to those now seen in SARS-CoV-2—a single amino acid change on its surface that made it better suited to infect cells in pseudovirus lab experiments.
But, in the end, Ebola didn’t go airborne. The outbreak was contained through good public health measures and medical care. (Here's how to stop the coronavirus from winning.)
The experts interviewed for this story said public concerns of mutations emerge with almost every pandemic. It could be because of fear of what’s unknown about this dangerous disease or simply because hazardous mutations make for a good story.
"With COVID-19 there are so many unknowns, and we can't tell a complete story. But as humans, we seek that complete story, and so we fill the gap,” says Seema Yasmin, director of research and education at the Stanford Health Communication Initiative. “Oftentimes we fill in the gaps with very sensationalist, very emotionally triggering information."
Raising the specter of a deadly mutation “is a wonderful thing to say to rev up interest, because it’s like a science fiction TV plot,” says Howard Markel, a physician and medical historian at the University of Michigan. “You'll see in popular accounts of influenza, for example, in magazine articles, that the 1918 flu mutated and became stronger. But there is absolutely no evidence to suggest that.”
A mutation that completely changes how the coronavirus behaves is unlikely. Both the flu and coronavirus are RNA viruses, and Racaniello points to other examples in this class—like HIV and measles—that have not fundamentally shifted their transmission behavior since they emerged.
“There's no precedent for any virus changing its fundamental way of transmitting,” Racaniello says.
More plausible, in the case of COVID-19, are slight mutations that render the virus suddenly unrecognizable to the immune system. In this scenario, people could be re-infected and vaccines—once developed—could be rendered useless over time. This is what happens with the seasonal flu. Every year, the virus changes slightly and we have to adjust our vaccines accordingly.
SARS-CoV-2 was already quite adept at spreading when it emerged in Wuhan in late 2019. It’s mode of transmission—through respiratory droplets and in sometimes asymptomatic people—was already sufficient to cause a devastating pandemic.
The future of the pandemic, experts say, will depend more on the actions we take to prevent the virus from spreading than on the intrinsic properties of the virus itself.
Claus Wilke, structural biologist at University of Texas Austin, thinks the worries over the G614 mutation are missing that point: “It’s not going to affect the two main questions that we have, which are, how can we prevent spread? And will a vaccine work?”