Since the beginning of the corona pandemic, scientists have been puzzling over where and how the Sars-CoV-2 coronavirus first spread to humans. Now, two new studies confirm that the long-suspected fish and wildlife market in Wuhan was in fact the starting point of the global pandemic. Evidence of this is provided by the geographic distribution of the very first Covid-19 cases in Wuhan, most of which are grouped around the market. Samples from market stalls also contained the virus. On the other hand, the genetic sequencing of the early cases shows that two genetic lines of the virus jumped from animals to humans in quick succession in November and December 2019.
The corona pandemic has now been underway for two and a half years. Its pathogen, the Sars-CoV-2 coronavirus, has spread from the Chinese city of Wuhan across the world since December 2019. But the origins of this virus and the circumstances under which it made the leap from animals to humans are still unclear. Comparative genetic analyzes suggest that the precursor to Sars-CoV-2 probably developed in bats. However, it is disputed whether it jumped directly from these to humans or via another animal as an intermediate host. The location of the species jump is also controversial: while some epidemiologists suspected the Wuhan fish and animal market from the start because there was close contact between people and the wild animals sold and slaughtered there, others believed that there was a virological laboratory in Wuhan the starting point. So far, however, there has been no clear evidence for any of these scenarios.
Concentration of the first cases around the Wuhan market
But now there is more clarity. Scientists have traced the coronavirus in two different ways and both research teams come to the same conclusion. According to this, the Wuhan animal market is the epicenter of the pandemic. There, Sars-CoV-2 successfully jumped twice from animals to humans. The first team led by Michael Worobey from the University of Arizona found evidence of this when they analyzed the beginnings of the virus spread geographically. To do this, the researchers examined the distribution of the first Covid 19 cases identified in Wuhan in December 2019. There was a clear cluster of cases in the immediate vicinity of the market. Even the patients who had no direct connection to this market lived on average no more than four kilometers away. “In a city larger than 7,700 square kilometers, the first cases were concentrated within a few blocks, with Huanan Market right in the middle,” Worobey said.
In the next step, the research team re-evaluated the data from samples taken by the Chinese authorities inside the fish and animal market after the outbreak of the pandemic. Walls, cages, market stalls and drainage channels were examined for the presence of Sars-CoV-2. However, the Chinese authorities did not publish the results of these analyzes until February 2022. When Worobey and his team evaluated this data and compared it with the first cases of Covid-19, there was a clear concentration of positive virus samples in the western part of the market. “This is the area where vendors were selling live mammals, including raccoon dogs, pig badgers and red foxes, just before the outbreak of the Covid-19 pandemic,” the researchers report. One of these stalls in the southwest corner of the market and another live wildlife stall nearby produced a particularly large number of positive samples. “These results suggest that there were infected animals in the Huanan market at the onset of the pandemic,” the team writes. As they noted, some of the earliest Covid-19 cases in Wuhan are also linked to this very area of the market.
Twice transmitted independently to humans
The second study followed the trail of the coronavirus genetically. A team led by Jonathan Pekar from the University of California at San Diego compared around 800 genome sequences from coronavirus samples taken from patients in Wuhan up to February 14, 2020. It was already known before that there were two virus variants in these early virus samples, lineage A and B, which differed in that they exchanged two RNA bases in the genome. So far, scientists have assumed that the species jump to humans took place only once and that line B must have developed from line A immediately afterwards. In the early samples, A accounts for around 35 percent, line B around 65 percent. However, through analyzes of mutation rates and family tree simulations, Pekar and his team come to a different conclusion: “Our analyzes show that lineage A as the original haplotype does not match the molecular clock data,” the researchers write. The origin of both lines in a common ancestor that made the leap to humans could only be traced in 0.1 percent of the model simulations.
According to the scientists, everything indicates that the two early variants of Sars-CoV-2 jumped independently from animals to humans. According to their reconstructions, this first species leap by a lineage B virus happened around mid-November 2019. The earliest documented case of Covid-19 with this virus variant is a vendor from one of the market stalls in Huanan Market who fell ill on December 10, 2019 and tested positive have been tested for Sars-CoV-2, as Pekar and his team determined. Line A of the coronavirus must have spread to humans a few days to weeks after virus variant B. Because the first known case with this type of virus occurred on December 15, 2019. The research team concludes from its analyzes that there were probably several unsuccessful transmissions of Sars-CoV-2 to humans before the start of the pandemic. It was not until November and December 2019 that two variants were able to persist in humans and were passed on.
“Our analyzes clearly indicate that the corona pandemic started with infections that jumped from animals sold in Wuhan’s Huanan market to humans,” says senior author Kristian Andersen of the Scripps Research Institute in La, who was involved in both studies jolla The theory of a virus that originated in a virus laboratory thus seems finally off the table.
Source: Michael Worobey (University of Arizona) et al., Science, doi: 10.1126/science.abp8715; Jonathan Pekar (University of California San Diego) et al., Science, doi: 10.1126/science.abp8337