As the new coronavirus has spread from person to person, and country to country, the virus has changed thousands of times. The vast majority of these changes are incremental. But last week, researchers at the Los Alamos National Laboratory posited that at least one variant had significantly mutated to become more contagious.
If true, this development could have major implications. The possibility of what’s known as a functionally significant mutation of SARS-CoV-2, which causes Covid-19, has intrigued and worried researchers and policymakers almost since the moment the virus was first identified. A new variant could, for example, hamper efforts to develop a vaccine or mean that people who’ve already had Covid-19 might face a greater risk of getting it again.
The Los Alamos hypothesis was quickly met with a rush of reactions ranging from raised eyebrows to dismissive skepticism from biologists and coronavirus experts around the world. The data, many said, just didn’t support such a big claim. Critics also felt the paper’s language oversold and sensationalized the actual findings.
“I find this hypothesis to be plausible but far from proven,” Trevor Bedford, a top viral-genome expert at Fred Hutchinson Cancer Research Center in Seattle, Washington, wrote on Twitter in response to the paper. He said he had been watching the mutation closely.
Los Alamos declined to comment. The federal research center was created during World War II to focus on national security.
The Los Alamos paper, which was published online prior to peer review, describes how researchers combed through a global database of SARS-CoV-2 variants. They found one that seemed to dominate quickly as the virus spread throughout Europe. This variant had several mutations that distinguished it from the Asian version. One was dubbed Spike D614G.
“It’s in an important piece of the virus, and we need to study it to determine whether or not it’s a concern,” said David Montefiori, a Duke University virologist and author of the study. “What we’re claiming is that this mutation needs to be studied aggressively, quickly,” he added. “We’re not trying to blow things out of proportion.”
Viruses replicate by copying themselves, and often they make mistakes. These mistakes become what are known as mutations. Most of these changes though, are the equivalent of a few words in an entire book, and so they don’t perceptibly change the virus.
The Los Alamos scientists set up a system to identify mutations that might be noteworthy, yielding the Spike D614G. The spike protein is critical: It’s the key the virus uses to enter and infect a healthy host cell before taking it over to churn out copies of itself. Vaccines and therapies often are designed to disarm exactly this portion of a virus’s operation. Some kinds of mutations, conversely, can make a virus much more able to spread rapidly. Others can change the nature of a virus, making it less or more dangerous.
“The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions, it rapidly becomes the dominant form,” the researchers wrote.
Monitoring these tiny mutations over time is also how researchers are able to track how the virus travels through the world, much like building a family tree. The Spike D614G mutation occurred right around the time the virus arrived in Europe and ended up seeding much of the outbreak there. Now it’s the predominant variant in Europe. In the U.S., this European version is prevalent on the East Coast, while the one originating in China was initially more present on the West Coast. The European variant has been gaining ground, however, fueling speculation it may have mutated in a way that makes it easier to spread.
The Los Alamos researchers note the increasing frequency of the D614G mutation and argue it demonstrates that the mutation makes it more transmissible than the original version. Genomics researchers say this is possible. But they also don’t rule out random chance. As Bedford puts it, the D614G version may be more common simply “because it got lucky in the European introduction,” seeding a massive Italian outbreak that quickly spilled over to the rest of Europe and the eastern United States and has now spread to Australia.
Much more data is needed to confirm which possibility is correct, including lab-study results that could show the virus infects cells more effectively in the test tube. Researchers also will be on the lookout for more epidemiological data to confirm that the D614G is becoming the dominant variant.
For now, drugmakers rushing to create a vaccine for the virus have signaled they haven’t seen anything to be concerned about. Ugur Sahin, the chief executive officer of Mainz, Germany-based BioNTech SE, said he has “no doubt that from a vaccinology standpoint, we don’t see mutations which could emerge as vaccine-escape variants yet.” Moderna Inc.’s chief medical officer, Tal Zaks, has expressed similar views.
And Roche Holding AG, one of the world’s biggest players in diagnostics, has said it hasn’t seen any mutation that would compromise the accuracy of its Covid-19 tests.
A weakness of the paper, critics say, is that there’s little lab data supporting the assertions it makes. It’s possible the D614G mutation does something important, but it isn’t clear what that would be and what it means, says Stanley Perlman, a top coronavirus researcher at the University of Iowa.
A significant mutation could potentially change the course of the illness, for example, by causing more-severe symptoms, said Jennifer Doudna, a University of California at Berkeley geneticist. But “there is no evidence that this increasing prevalence corresponds to more-severe disease outcomes.”
Other research suggested SARS-CoV-2 is somewhat more stable than other kinds of viruses. A Scottish study published this week in the journal Virus Evolution noted there have been just over 7,000 documented mutations thus far, a rate about a third that of the flu. The paper suggested these mutations aren’t likely to significantly affect the virus’s biology.
“It’s important to remember that viruses mutate,” said Oscar MacLean, a lead author on the study and researcher at MRC-University of Glasgow Centre for Virus Research. “That’s what they do all the time.”
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