When SARS-CoV-2 made the leap to humans late last year, it was remarkably well adapted to spread among us. But that doesn’t mean it can’t get worse, as the virus will undoubtedly pick up new mutations as the population grows, some of which could make it more dangerous for humans. In fact, a draft paper recently posted online claimed to have evidence that a more contagious strain of SARS-CoV-2 had already evolved.
But the evidence is far from conclusive, and scientists have scrutinized both the paper and its accompanying press coverage.
The coverage in the press
The Los Angeles Times had coverage typical of the early response to the concept paper, with the headline: “Scientists say a now-dominant strain of the coronavirus appears to be more contagious than the original.” But Tuesday’s coverage had been roundly criticized by scientists, and awareness of the paper’s problems gradually increased. This pushback came from sites devoted to health news analysis and from mainstream newspapers. But even after these criticisms were published, new articles still proclaimed increased contagiousness.
All this was set in motion by a draft article posted to the bioaRxiv — one with a title that seemed to support the fears surfacing in the worst headlines: “Spike Mutation Pipeline Reveals Emergence of a More Transmissible Form of SARS CoV-2.”
Scientists’ responses were critical of both the paper’s authors (one in the US and the other in the UK) and the media coverage the paper has received. As far as the media is concerned, the scientists seem to have two main points for their criticism. The answer is: typified by Angela Rasmussen of Columbia University, who laid out the issues in the early parts of a Twitter thread. Rasmussen and other scientists believe that many reports have not been careful when evaluating a draft paper that has not been peer-reviewed. As a result, the reporters did not take the time to understand the data enough to acknowledge the study’s limitations.
This has been a recurring challenge during the pandemic as scientists rushed to post preliminary data and analysis online in hopes that health authorities can benefit. But these concepts can vary widely in quality, and the ones that grab attention aren’t necessarily the ones that will pass peer review without significant changes.
People tend to see peer review as a way to ensure that a paper’s data is valid. But it usually fulfills an equally important function: to determine whether a paper’s data supports the conclusions its authors draw. In the case of Rasmussen’s critique and a series of additional problems highlighted by Bill Hanage of Harvardthe draft paper falls short in that regard – leading to press coverage that is overly gullible.
What’s in the design?
The paper was made possible by something that just wasn’t possible until recently: Researchers are continuously sequencing patients’ SARS-CoV-2 genomes and posting the results online with no restrictions, so others can analyze the data. Essentially, we can track the evolution of the virus as it spreads worldwide. Some of these mutations are not relevant to the behavior of the virus, but may be useful in monitoring how specific versions of the virus spread both within and between populations and may ultimately be useful in detecting sources of infection.
But there is a chance that some of these mutations also change the biology of the virus and thus are subject to evolutionary selection. For their concept paper, the researchers analyzed every viral genome available at the point of analysis in April and used that to look for signs of evolution. Among other things, they looked for indications that a mutation is becoming more common in a population, which could be a sign that it increases the spreading capacity of the virus.
They also looked at things like mutations that will alter the infamous spike protein in a way that could alter the immune system’s ability to recognize the virus and found that some individuals are likely infected with two viral strains at once, leading to new combinations of the mutations each strain carries. Strangely enough, the latter is easiest to detect in Belgium.
But the title- and cover-worthy finding was an indication that a single mutation was much more common over time. At the beginning of March, the mutation was found in only a small percentage of the total available genome, mainly in Europe and South America. Later in March, it was found in 29 percent of the total available genomes. In individual populations, the mutation typically grew dramatically over time, as shown in the graphs below.
In a study of patients in a specific UK city, the mutation was not associated with medical outcomes, suggesting it did not alter the course of infections. Instead, the authors conclude that the mutation could increase the infectivity of the virus, explaining why its frequency increased in many populations. To be clear, the data is consistent with that explanation.
The problem is that it is also consistent with other statements†
Not so fast
For starters, the number of genome samples per site is generally quite small, and it’s not clear how the virus’s sources were chosen for genome sequencing. Most sites also experienced complicated growth and decline trajectories over the study period. All of these factors can make a relatively small effect appear larger than it is, although the large number of locations with similar patterns makes this less likely.
as Hanage be aware, we also know very little about how the virus has spread between different areas. The lack of details on how often the virus was introduced and how often additional resources traveled between locations leaves open the possibility that the pattern is a product of founder effects and frequent reintroductions from certain areas.
and if Rasmussen emphasized, sometimes mutations occur for reasons other than to provide a large selective advantage. We’ve apparently been here before, where a mutation was believed to increase the infectiousness of the Ebola virus, but testing the mutation in animals showed it didn’t make any difference. In other words, proof consistently having an idea is not enough to confirm that idea without additional data. Since the research team was only doing computer analysis of genome sequences, the paper couldn’t possibly provide more convincing evidence.
So the author’s conclusion that there is an “emergence of a more transmissible form of SARS-CoV-2” is not convincingly supported by the paper’s data. And that’s a problem that would normally be solved by peer review. But for now, much critical information will reach the public without the benefit of that vital step.