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Washington: A research paper from scientists at Los Alamos National Laboratory, not yet peer-reviewed, reports that one strain of the novel coronavirus has emerged in Europe and become dominant around the planet, leading the researchers to believe the virus has mutated to become more contagious.
The bold hypothesis, however, was immediately met with skepticism by many infectious-disease experts, and there is no scientific consensus that any of the innumerable mutations in the virus so far have changed the general contagiousness or lethality of COVID-19, the disease caused by the coronavirus.
The Los Alamos scientists, led by computational biologist Bette Korber and working in conjunction with researchers at Duke University and the University of Sheffield in the United Kingdom, examined a global database of strains of SARS-CoV-2, the virus that causes the disease. According to their analysis, one strain featuring a mutation dubbed Spike D614G quickly out-competed other strains after it appeared in Europe.
The mutation affects the structure of a protein, called the spike protein, that is critical to the virus' ability to infect human cells. The researchers believe this structural change enhances infectivity.
"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 authors write. They describe the mutation "increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread."
Scrutiny by research community
The paper will now have to survive the intense scrutiny of a research community trying to deliver urgently needed information while remaining scientifically rigorous.
Francis Collins, director the National Institutes of Health, said in a brief email that officials there are aware of the paper, and that it "draws rather sweeping conclusions" about the mutant strain.
The Los Alamos scientists' goal was to set up an early-warning system for identifying potentially important mutations in the SARS-CoV-2 virus. Like all viruses, this pathogen makes mistakes when it copies its genetic material. But, much the way changing a single letter rarely affects the content of a book, most mutations don't meaningfully affect the behaviour of a virus.
The consensus has been that strains of the coronavirus are functionally the same, even if they look genetically different. The fact that the coronavirus is mutating is unsurprising, because all viruses mutate as they replicate. So far, this virus appears relatively stable, according to virologists, but the vast extent of the spread of the coronavirus has given it ample opportunity to evolve.
When the Los Alamos research team examined thousands of genome sequences uploaded to the Global Initiative on Sharing of All Influenza Data database, they identified several mutations that distinguished the version of the virus circulating in Europe from the version that originated in Wuhan; the Spike D614G mutation was among them.
"If there were to be something that influenced transmissibility, then the spike protein is the place I expect to find it," said William Hanage, a Harvard epidemiologist who specialises in the evolution of infectious diseases.
But Hanage, like many other outside researchers, was not convinced this mutation actually affects the virus' ability to infect people. Though the mutated form has become the dominant strain, that could be a consequence of a "founder effect," Hanage said.
Case of Italy
When the mutated version arrived in northern Italy, an older and more susceptible population was unable to contain it. "It's the fox that got into the henhouse," Hanage said.
Hanage pointed to Washington state, where the virus was recognised relatively early and public health measures have proved effective at reducing cases. Both strains were circulating in the state by mid-March - and now, cases of both strains appear to be falling at the same rate. If the European strain really were more transmissible, he would expect it to crowd out all other versions.
The national lab did not make Korber, the lead author of the new paper, available for an interview.
Credible study
One prominent scientist, Stanley Perlman, a virologist at the University of Iowa who played a role in naming the coronavirus, said Tuesday that the Los Alamos study looks credible.
"It certainly looks like it is more readily transmissible. Viruses mutate to become more transmissible, but not generally to become more virulent (unless this enhances transmissibility)," Perlman said in an email.
The research community is far from embracing any of the studies that haven't gone through the rigorous peer-review process before publication in a journal. Hanage said people should view these preprint papers sceptically, because the findings have not been reviewed and potentially challenged by other researchers.
"This is science in an extraordinarily difficult and intense time," Hanage said.
Same pattern in multiple locations
David O'Connor, a virologist at the University of Wisconsin, said the most interesting feature of the Los Alamos research is that the same pattern was seen in multiple locations. But he said "significant caution is warranted" because the data was not collected randomly. The vast majority of SARS-CoV-2 genomes in online databases come from Europe and North America, meaning strains from these regions are overrepresented in research.
The Los Alamos scientists did not find evidence that patients with the mutant strain of the virus were more likely to be hospitalised. An increase in contagiousness does not necessarily correlate with greater lethality. The opposite is actually more common as viruses mutate, and some experts speculate that COVID-19 could become a milder disease over the course of many years as the virus circulates through the human population.
Since the early days of the outbreak in China, scientists have known that SARS-CoV-2 is unusually contagious - more so than influenza or a typical cold virus. Scientific estimates of the reproduction number - the R0, which is the number of new infections that each infected person generates on average - have varied among different communities and different points but have generally been between 2 and 4. That is significantly higher than seasonal influenza.
Criticism of hypothesis
One criticism of the Los Alamos hypothesis is that there could be other explanations for why one strain of a virus becomes dominant. University of Wisconsin virologist Thomas Friedrich, who has spent years studying the evolution and transmission of the Zika virus, said a virus that makes its way into a highly susceptible population - for example, Europe in January - will spread like wildfire, quickly becoming the dominant strain in the region.
That doesn't necessarily mean it picked up a mutation that boosts its ability to infect people. It could mean the virus just got lucky - and humans got caught off-guard.
When the Zika virus migrated across the Pacific to the Americas and began to cause birth defects, scientists thought it may have picked up some kind of "microcephaly mutation" right when the outbreak in the Americas began, Friedrich said.
Experiments showed the virus strain did carry a mutation, and was able to cause nerve tissue damage when it was injected into mouse brains. But when scientists were able to study other variants, they found many of them also had the ability to harm foetuses. What made the virus strain in the Americas so dangerous wasn't the mutation, but that people on this side of the Pacific had no immunity.
