Los Angeles - The global outbreak that has sickened nearly
100 000 people across six continents may actually be fueled by two
variants of the same coronavirus: one older and less aggressive and a
newer version whose mutations may have made it more contagious and
more deadly, according to a controversial new study.
Chinese scientists who compared the genetic sequences of 103 viral
samples from patients infected with Covid-19 said their evidence
suggests that the virulent version of the coronavirus - which they
tagged the "L-type" version - was the dominant strain in the earliest
phase of the outbreak that began in Wuhan, China, late last year.
That strain, they said, appeared to recede as the epidemic
progressed.
But among samples collected later, as Covid-19 spread across China
and into other countries, a variant of the virus they dubbed the
"S-type" was more common, the scientists reported. They suggested
that the genetic makeup of the S version more closely resembles
coronaviruses circulating in bats and pangolins, the animals that are
thought to have incubated the virus before it jumped to humans. And
they surmised that it is a less virulent version.
The findings suggest the S-type version of the coronavirus may have
escaped its animal hosts earlier than previously believed - and that
it may have been circulating longer without causing enough illness to
set off alarm bells.
The Chinese scientists reported their analysis Thursday in the
journal National Science Review. The team was led by Peking
University's bioinformatics researcher Jian Lu in Beijing.
The study authors acknowledged that their conclusions are very
preliminary and are based on a very small sample of viruses. The
variations they found will need to be observed in many more specimens
taken from other patients, and their genetic differences will need to
be compared with physicians' reports and epidemiological notes. Only
then can their suspicions can be confirmed, they wrote.
Officials at the World Health Organization warned that "it's
important we don't overinterpret" the scientists' findings.
"It's got a slightly different signature, but it's not a
fundamentally different virus," said Mike Ryan, the WHO official
coordinating the agency's response to the Covid-19 epidemic.
Some scientists were far more critical, with some calling for the
paper to be retracted.
The new analysis comes from scientists in a relatively new and
fast-moving field that's devoted to the genetic investigation of
disease-causing germs.
Using a technique called phylodynamic analysis, researchers collect
and sequence the genomes of many samples of a given microbe and scour
them for tiny substitutions in their DNA or RNA. By tracking those
genetic shifts, they can reconstruct a rough picture of a germ's
passage through a population, and detect turning points along the
way.
The authors of the new study compared genetic sequences of viral
samples taken from 27 patients in Wuhan, 33 patients from elsewhere
in mainland China, three from Taiwan and 40 from patients outside
China.
Comparing all those samples to those taken from bats, they found
relatively little evidence of variability. That suggests the novel
coronavirus has circulated in humans for only a few months, changing
little as it jumped from person to person and replicated itself, they
wrote.
But when the scientists compared the 30,000 nucleotides of each
sample to one another and focused on finding differences among them,
they found a much greater degree of variability. That's a sign that
the changes in the virus since it began to infect humans were "much
larger than previously estimated," they wrote.
Of the 103 viral genomes they scoured, 70 per cent were of the L-type
variant. But by early January, the scientists wrote, it appears that
"human intervention" - possibly the "rapid and comprehensive
prevention and control measures" adopted by China - had begun to
limit the spread of this strain.
By late January, doctors and health authorities were on high alert
and testing widely for Covid-19 infection. But at that point, the
Chinese scientists speculated, they were collecting samples from
patients who were sickened by the older, less dangerous S-type
version of the virus.
Some geneticists who weren't involved in the study argued that the
data could support an alternative interpretation: that the virus has
simply spread more widely than they had realized, picking up random
mutations along the way. Those mutations may or may not make the
virus behave differently.
If the S-type of the virus is the older version that was circulating
first, a final mystery remains: Why would the majority of samples
taken from the initial patients in Wuhan have fallen into the L-type
category? Shouldn't there be more S-types in the mix?
This is where the Chinese scientists make a hotly debated leap: They
surmise that the newer L-type version probably picked up more
mutations, and evolved further from the bat coronavirus from which it
originated, because it either infects people more readily or it
replicates more vigorously once it infects.
In other words, it's more transmissible or more aggressive - or both.
University of Edinburgh geneticist Andrew Rambaut urged caution about
that conclusion. When genetically sequenced samples represent a small
and haphazardly collected subset of all infections, the kinds of
genetic variations noted by the scientists are "entirely expected,"
he wrote on Twitter.
To claim that such mutations necessarily make a virus behave
differently, he added, "is a flawed inference."
A group of researchers from the MRC-University of Glasgow Center for
Virus Research in Scotland offered a more detailed rebuttal of the
new paper. Among other things, they said the study authors
misinterpreted their data and failed to account for limitations in
their statistical methods.
"Given these flaws, we believe that Tang et al should retract their
paper, as the claims made in it are clearly unfounded and risk
spreading dangerous misinformation at a crucial time in the
outbreak," the Glasgow team wrote.