And the World Became Still Again

Scientists trying to zero in on the origins of the Covid-19 pandemic have recently filled in some critical blanks. The findings aren't a smoking gun and might not convince some people who think the virus escaped from a laboratory in Wuhan, China. But they provide the sharpest view yet of the early days of the outbreak.

In two February preprint papers, first reported by the New York Times, researchers traced the spread of the SARS-CoV-2 virus, the pathogen that causes Covid-19, in 2019 in Wuhan. One study looked at initial infections at the Huanan Seafood Wholesale Market, where the first cases were detected. The other examined the genomes of the earliest strains of the virus. Around the same time, researchers from the Chinese Centers for Disease Control and Prevention published their own findings from virus samples they collected from animals and the environment around the market in early 2020.

In addition to seafood, vendors at the market sold live animals, including those collected from remote wilderness areas.

Together, the studies connect the dots of transmission at the epicenter of the pandemic, observing that the virus likely made the leap from animals to humans more than once. "Once you understand that there were infected animals in the market, then multiple spillovers are not just a possibility, they're what you would expect at that point," Robert Garry, a virologist at Tulane University and a co-author on both papers, told Vox.

The studies' conclusions contradict some early reports that the Huanan market was not the original locus of Covid-19. The results also echo how scientists think the first SARS virus spread to humans in 2002. According to Garry, they make the possibility that the outbreak began with a leak from the Wuhan Institute of Virology much less plausible.

The idea that a world-stopping virus escaped from a laboratory has sparked a heated debate among scientists, pundits, and politicians, fueled by accusations of bad faith, malfeasance, and cover-ups.

However, while researchers have narrowed down the location in the market where the outbreak likely began and have identified several potential animal hosts, they still haven't found the specific animals that were infected. And though scientists have found several related viruses in the wild, they haven't found one yet that they think could have directly spawned SARS-CoV-2.

But even without knowing exactly which animal ignited the pandemic, the new studies offer critical lessons in how new diseases emerge and point to potential routes for averting another global catastrophe.

Scientists have zeroed in on the stall where Covid-19 likely emerged

The recent studies investigated the earliest days of the pandemic, tracing the initial wave of infections in China. In particular, researchers paid close attention to the Huanan Wholesale Seafood Market. It's part of the bustling live animal trade in Wuhan, a city of more than 8 million people. By one estimate, more than 47,000 animals across 38 species were sold in the city between May 2017 and November 2019, often suffering "poor welfare and hygiene conditions." Bringing animals together from far-flung regions with inadequate sanitation and selling them to people for food, fur, or as pets is a recipe for breeding new diseases.

In one of the studies, researchers examined photographs, sales records, social media, genome sequences, surveys, and infection patterns around Wuhan in 2019. The researchers found not only that the initial Covid-19 cases emerged at the market, but that the "overwhelming majority were specifically linked to the western section of the Huanan market, where most of the live-mammal vendors were located." The highest concentration of positive SARS-CoV-2 samples came from a single stall.

That section of the market was known to be selling Asian raccoon dogs (Nyctereutes procyonoides), hog badgers (Arctonyx albogularis), and red foxes (Vulpes vulpes) at the time of the outbreak, all animals that are susceptible to SARS-CoV-2.

Researchers detected more SARS-CoV-2 in the environment around specific live animal sellers at the Huanan Wholesale Seafood Market in Wuhan, China.

Worobey et al./Zenodo.org

Researchers also studied the viruses themselves. From looking at the genomes of the viruses among the collected samples, they found that there were two distinct lineages of SARS-CoV-2, dubbed A and B, that were infecting people at the outset. Scientists think the B lineage formed after A, though B is not necessarily a descendant of A. Researchers estimated the probability that both lineages came from a single origin as 3.6 percent, meaning they likely followed separate evolutionary paths.

The first known human Covid-19 case was likely caused by B, which also became the dominant strain. The first known human infection caused by A occurred a week later.

The study from the Chinese CDC also confirmed that both lineages were spreading around the market. Together, the papers paint a new story of the early days of the pandemic, as Carl Zimmer and Benjamin Mueller at the New York Times wrote:

These findings came as a surprise. In the early days of the pandemic in China, the only Covid cases linked to the market appeared to be Lineage B. And because Lineage B seemed to have evolved after Lineage A, some researchers suggested that the virus arrived at the market only after spreading around Wuhan.

But that logic is upended by the new Chinese study, which finds both lineages in market samples.

The distinct genomic sequences and the timing of the infections point to a scenario where SARS-CoV-2 made the jump into humans on two separate occasions at the Huanan market. One of the new papers raised the possibility that there may have been even more spillover events there.

Researchers say the results add weight to a natural origin of the virus and counter the lab leak theory

The latest round of research does have its limitations. Scientists noted that they may have missed some infections, since many Covid-19 cases don't cause any symptoms at all. "For every one of the COVID-19 cases who became ill enough to be among the 174 hospitalized patients with illness onset in December of 2019, there were likely more than ten milder cases that went unnoticed," researchers wrote in one of the preprint papers, neither of which has been peer-reviewed yet.

They are also working more than two years out from the initial outbreak, limiting what they could examine. And while they traced the virus to a specific area with live animals, the Chinese CDC observed that "no SARS-CoV-2 was detected in the animal samples from the market." The SARS-CoV-2 virus likely stems from a virus found in bats, and the most similar known bat virus was found last year in Laos.

"I think what they're arguing could be true," Jesse Bloom, a Fred Hutchinson Cancer Research Center virologist, told the New York Times. "But I don't think the quality of the data is sufficient to say that any of these scenarios are true with confidence."

To date, it's still unclear which animal served as the intermediate host that transmitted it to humans. And at this point, it may not be possible to find out since the specific infected animals were likely culled. "You'd have to be a time traveler or something like that to go back and see," Garry said.

Raccoon dogs were among the animals sold at the Huanan Seafood Wholesale Market and are susceptible to SARS-CoV-2.

Raimund Linke/Getty Images

However, the findings do challenge the theory that the virus escaped from a laboratory. The lab leak hypothesis holds that SARS-CoV-2 escaped from the Wuhan Institute of Virology, a facility roughly eight miles from the Huanan market. Proponents of the theory point to several factors. Researchers there were known to be studying bat coronaviruses. Specifically, they documented a bat coronavirus called RaTG13. Discovered in 2013, it has a genetic sequence with 96 percent overlap with SARS-CoV-2.

Scientists at the Wuhan Institute were also conducting experiments under lower safety conditions than most scientists would recommend for respiratory viruses. Some researchers argue that the types of experiments they were conducting constitute gain of function, where a virus is engineered to become more infectious.

Circumstantially, pathogens have escaped from Chinese laboratories before. And the Chinese government's actions have added to the suspicions. They may have covered up the extent of the original outbreak, and international investigators have complained that the Chinese government still has not been fully transparent with what happened during the early days of the outbreak.

However, there appears to be no evidence the Wuhan Institute of Virology had an actual isolated sample of SARS-CoV-2, nor did they have any live ancestor to the virus, including RaTG13. They only recorded the genetic sequence.

The latest studies show also that the earliest clusters of the virus were concentrated in a specific area of the Huanan market. If the virus were introduced by a person from outside the market, environmental samples testing positive for SARS-CoV-2 would likely have been spread out more through the building.

In addition, the fact that two distinct lineages emerged in the early outbreak would require that someone from the lab would have had to introduce two different versions of the virus to the lab on two separate occasions.

"The simplest explanation is that infected animals infected people," Garry said. "You have to go through quite a bit of mental gymnastics to go 'it came from the lab to the market,' and you have to believe that happened twice."

We may never get a satisfactory answer, but we can prevent future pandemics

The frustrating reality is that a definitive origin story of Covid-19 may never emerge, and many of the critical bits of evidence are gone. The Huanan market has since been closed and sanitized and what little goodwill there was between Chinese authorities and outside investigators has dried up. This might be the closest we ever get to solving the mystery, and it won't convince everyone.

A World Health Organization team investigated the Wuhan Institute of Virology last year. While they found no evidence that SARS-CoV-2 originated there, some members complained that authorities did not cooperate enough with the probe.

Hector Retamal/AFP via Getty Images

But there are important lessons for how pandemics could arise. New diseases do naturally jump from animals to humans on occasion, but human action is heightening these risks. Farmers, property developers, miners, and poachers are encroaching into once-isolated wilderness areas, increasing the chances of contracting a novel disease from animals.

And the wildlife trade is particularly troublesome. The Huanan market illustrated what can happen when a variety of live animals are transported across vast distances and then stored in cages close to each other. It increases the odds of pathogens jumping between animals, mutating, and spreading to humans.

In such circumstances, spillovers are hardly natural events. However, it also means that measures such as restricting illegal wildlife trade and improving sanitation would help prevent future outbreaks.

At the same time, there are a number of things scientists around the world can do to enhance security around laboratories and clamp down on the possibilities of dangerous diseases escaping. That includes tactics like more robust biosafety protocols and greater transparency around virus research.

A lab leak and a spillover may not be equally likely, but the devastation of the Covid-19 pandemic highlights how important it is to close off both of these routes. It's not too soon to think about heading off the next global disease.

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Source: https://www.vox.com/22961822/covid-19-origin-coronavirus-wuhan-china-market-lab-leak

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