The origin of the SARS-CoV-2 virus, which caused the COVID-19 pandemic, has been hotly debated.
The debate has caused substantial difficulties in Australia-China relations, with Foreign Minister Marise Payne’s call for another investigation into its origin being viewed by China as a hostile act.
What is beyond doubt is that the virus’s closest relatives are found in bats. How, where and when the virus spread to humans is the controversial question.
One widely supported hypothesis is that the overflow occurred in Wuhan’s “wet markets”, where many species of wildlife from all over China are kept under overcrowded conditions.
However, there is no evidence that the bat species in which the closest relatives of SARS-CoV-2 are found were sold in Wuhan’s wet markets at any time in the two years before the pandemic. This hypothesis requires the existence of a “bridge host”, another species which becomes infected by overflowing the original bat hosts, then transmits the virus to humans.
Bridge hosts are well known in many emerging human diseases. For example, the Hendra virus, which my group is studying, has flying foxes as a reservoir. Hendra spills over onto the horses with some frequency. Horses then amplify the virus as a bridge host and can infect humans.
Fortunately, this is extremely rare, with only seven known cases. Tragically, four of those people have died. Hendra has never been known to spread directly from flying foxes to humans.
Read more: I was the Australian doctor for the WHO COVID-19 mission in China. Here’s what we found about the origins of the coronavirus
More evidence that a lab leak is highly unlikely
A second hypothesis, much more controversial, is that the origin of the pandemic is the result of a “laboratory leak”.
Wuhan has one of the most sophisticated virological laboratories in China, and the laboratory works on bat viruses. The suggestion is that the virus may have inadvertently been released into the general community through one of the workers. No direct evidence supports this hypothesis.
New preprinted study, published online this month, provides strong evidence to support the ‘natural overflow’ hypothesis, with results difficult to reconcile with the ‘lab leak’ hypothesis .
The study has not yet been peer reviewed. But it is based on a detailed examination of the genetic sequences of the first two lines obtained from people infected in late 2019 and early 2020.
For convenience, these two lines are referred to as A and B. The two lines differ by only two nucleotides (letters of the genetic code) at two different key sites in the genetic sequence.
If there was a single laboratory escape event, the separation between lines A and B must have occurred after the laboratory escape. We would therefore expect to see a substantial number of intermediate lines, with the A line nucleotide on one site and the B line nucleotide on the other site.
However, if almost all of the genetic sequences obtained in humans are from the “pure” A line or from the pure B line, this suggests that there have been at least two different spillover events, either directly from bald. mouse, or via bridge hosts.
And the evolution of both lineages happened before humans were infected.
The researchers uploaded all of the complete SARS-CoV-2 genetic sequences that had been recorded into a widely used genomic database. Of these sequences, 369 were of line A, 1,297 were of line B and only 38 were intermediates.
Read more: Why it will soon be too late to know where the COVID-19 virus came from
Genetic sequencing is not perfect. Careful examination of the 38 intermediates strongly suggested that they were more likely to be pure A line or B line sequencing errors than to be true intermediates.
The genetic evidence therefore strongly suggests that there were at least two distinct spillover events in human populations, one from the A lineage and the other from the B lineage.
Did a human bring SARS-CoV-2 to wet markets?
The data doesn’t tell us there were only two overflow events – there may have been more. They also don’t tell us whether these overflows occurred directly from bats, or whether some or all of them occurred via an intermediate bridge host.
A Nature News article suggests that this evidence points to the spillover happening via the wildlife trade, but I think it goes too far.
While some of the wildlife sold in the Wuhan wet market may indeed be infected with SARS-CoV-2 (e.g. raccoon dogs and mink), there is no evidence that any of the species sold on the market was infected.
Most of the earliest human viral sequences (all of the B lineage) were collected from the Wuhan seafood market, but wet markets and slaughterhouses are well known to be places where the SARS-CoV-2 virus is found. spreads very well from human to human.
So, it may have been a human who brought the virus to the Wuhan seafood market, rather than a species of wild animals.
One thing we do know is that this pandemic is caused by human contact with another species infected with the virus.
It is not known whether this was a bat or a bridge host, and whether this contact occurred in a wildlife market, or in a bat cave, or elsewhere.
Nonetheless, as humans increasingly encroach on wildlife habitats, and as wildlife increasingly come into close contact with humans, we can expect further fallout and pandemics.
Read more: How Viruses Mutate and Skip Species And why are “overflows” more and more frequent?