Don’t Panic Over the Latest Coronavirus Mutation Headlines

Understanding the recent news about the D614G mutation

Image: koto_feja/Getty Images

Recent alarming headlines raised concerns that a new mutation in SARS-CoV-2, the virus that causes Covid-19, was making it somehow more potent. A Twitter moment blared: “More infectious coronavirus strain found in Malaysia.” Bloomberg’s headline declared: “Southeast Asia Detects Mutated Virus Strain Sweeping the World.” Meanwhile, Malaysia’s director general of health Noor Hisham Abdullah said in a Facebook post on August 15 that the mutated form could be 10 times more infectious.

As is often the case with scary headlines, these did not tell the whole story and are worth taking with a hefty pinch of salt. The mutated form of the virus has been the dominant form in Europe, the United States, and Oceania for several months, and it has more recently emerged in Asia.

The mutation in question is known as D614G, which refers to a single change in the amino acid sequence that makes up the genetic information of the virus. The amino acid that’s usually at position 614, aspartic acid (known as “D”) is switched out for glycine (known as “G”). And while it’s important to take note of changes like that, there’s currently no evidence suggesting that it makes the virus more contagious and dangerous.

Or, as Bill Hanage, PhD, associate professor at Harvard T.H. Chan School of Public Health’s Center for Communicable Disease Dynamics, put it to the Coronavirus Blog: “It’s not the thing to be writing, ‘Oh my god, siren, siren, siren.’”

Mutations occur naturally as viruses replicate. Each time a virus does so, it has to copy its genome, and sometimes this process results in errors. Some mutations are “neutral” and have no effect whatsoever, some are bad and kill the virus before it has a chance to replicate, and others do have an effect that changes the virus’s characteristics. But as Nathan Grubaugh, PhD, of the Yale School of Public Health, explained in a previous article I wrote for Elemental, for a mutation in a single viral particle to have an effect on an ongoing outbreak, it has to be passed on to future copies of the virus on a large scale. And for that to happen, the mutation must improve the virus’s ability to survive and replicate.

The D614G mutation was first flagged at the end of April in a preprint uploaded to bioRxiv by a team led by Bette Korber, PhD, of the Los Alamos National Laboratory. The preprint, which had not yet been peer-reviewed, described a method of identifying potentially dangerous mutations in the novel coronavirus. This method had singled out the D614G mutation, and it was deemed as being “of urgent concern.” When the variant of the virus with this mutation is introduced to new regions, the authors explained, it rapidly becomes the dominant form. The mutation also occurred in the virus’s spike protein, well known for its crucial role in infecting human cells.

By July 30, that paper had been peer-reviewed and accepted into the journal Cell. It shows that the SARS-CoV-2 variant with this mutation has indeed become the dominant form globally, that its dominance within regions may suggest an increased ability to survive and replicate, and that it’s associated with higher viral loads in patients who have it.

But critics of the paper say that the evidence doesn’t show that the mutation has an impact on the transmissibility, infectiousness, or disease severity of the coronavirus. In other words: Sure, it appears that the mutation has become more prevalent, but it’s not clear why. The question now is: How did this mutation get to be so fortunate? Was it really because it makes the virus more transmissible or infectious in some way, or was it, as Hanage puts it, “genuinely dumb luck?”

A critical commentary on the study also published in Cell, co-authored by Hanage, noted: “Virus mutations can rise in frequency due to natural selection, random genetic drift, or features of recent epidemiology. Because these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic.” The commentary’s lead author is Grubaugh, and Angela Rasmussen, PhD, of Columbia Mailman School of Public Health, is a co-author.

Another possible explanation as to why the mutation is so prevalent is that it was introduced to the U.S. multiple times by many individual travelers from Europe. It’s well established that most U.S. cases came from Europe, and if the mutated virus was already spreading there, then it’s possible that it took over in the U.S. not because it had some special ability, but simply because there were just so many travelers who brought it stateside.

Another complicating factor is known as the “founder’s effect.” It suggests that most of the transmission in a population is caused by just a small subset of infected people, which means that, in the U.S., a small bunch of people who were infected with the mutated variant spread it to the majority of other people. If this were the case, then it would make sense that the mutated variant was the most prevalent one in the U.S., but it wouldn’t necessarily mean that the variant was more transmissible.

In the Cell paper, Korber and her colleagues also showed evidence that people with the mutated variant have higher viral loads, suggesting that the mutation made the virus more infectious. Other teams have found this as well. But don’t jump to conclusions, caution the authors of the commentary: Higher viral load doesn’t always mean more severe disease, and Korber’s team didn’t see any correlation between the mutated virus and hospitalizations.

Colin Parrish, PhD, a professor of virology at the Cornell University College of Veterinary Medicine who was not involved in the study or commentary, tells the Coronavirus Blog that “mutations are inevitable, and that some of those are likely to be ‘human adaptive,’ but it is impossible to predict whether those will change either the severity or transmissibility of the virus.” If this mutation had a major effect, he says, we would have seen it in the data on viral spread globally, but he is “not aware of any major changes in those properties.”

On Monday, Paul Tambyah, MD, senior consultant at the National University of Singapore and president-elect of the International Society of Infectious Diseases, told Reuters that recent evidence suggests the new mutation may make the virus less lethal, citing a decrease in death rates. Experts interviewed by the Science Media Centre, however, caution that there’s no evidence that the mutation is the reason for the decrease. “It is certainly the case that the case fatality rate is falling across the world,” said Paul Hunter, PhD, professor in medicine at the Norwich School of Medicine, University of East Anglia. “There are, however, other very good explanations for this decline.”

In addition to Singapore, the virus with the D614G mutation has recently been detected in Malaysia, the Philippines, and elsewhere in Southeast Asia. “Keep an eye on what happens in these places,” says Hanage. Southeast Asia is, compared to the Americas, handling coronavirus outbreaks very well, and this means that there will be fewer introductions of the mutated variant into the population. In time it will become clear whether the variant actually is more transmissible or severe.

“Most introductions go extinct,” he says, “but those that don’t go big in a big way.”

Editor, Medium Coronavirus Blog. Senior editor at Future Human by OneZero. Previously: science at Inverse, genetics at NYU.

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