How did the pandemic begin? WHO team to seek answers in China

At the end of October, a team of researchers from the World Health Organization (WHO) finally sat down – virtually – with a group of Chinese experts to kick-off a long-term in-depth study into the origins of the coronavirus and how it entered the human population.

Next month – a year after China reported its first death in Wuhan from what was then considered a “mysterious” new illness – the 10 international experts from Denmark to Qatar will finally travel to the country to make in-depth “epidemiologic, virologic, serologic assessments” of people and animals.

Under the supervision of the WHO and the government of China, the team will travel to central China to gather evidence and explore how the virus appeared in the city, laying the groundwork for further study into how and where COVID-19 might have begun.

“The current COVID-19 pandemic shows the devastating impact emerging zoonotic diseases can have on societies,” the study’s terms of reference read. “As the pandemic continues to unfold, understanding how the epidemic began is essential to prevent further SARS-CoV-2 virus introductions and help prevent introductions of new viruses in the future.”

The experts will build on research conducted over the past year, as well as historic data from the SARS-CoV-1 outbreak in 2002, to work out how the new coronavirus, known as SARS-CoV-2, first emerged in animal hosts and later spread to humans.

But as the trip gets nearer, the origins of the virus are being hotly contested by one of the study’s key partners – the government of China – underlining the political nature of the pandemic and the challenges of investigating the origins of a disease that has now killed more than 1.7 million people around the world and devastated economies.

“WHO has put together a team to go to China and to work with colleagues in China to investigate the origins question but that is of course going to require a lot of cooperation with the Chinese government and scientists in China,” said Angela Rasmussen, a virologist at the Columbia University School of Public Health. “It’s going to be a very complicated political situation and political context in which to do a rigorous scientific investigation.”

Market research

Cases of the coronavirus first began appearing in Wuhan in late 2019, with Chinese media reporting the existence of a “mysterious” new respiratory illness among the city’s residents and suggesting a link to the Huanan market, which sold seafood but also a wide range of other animals including exotic wildlife.

The first phase of the study will look at one of the most important and confounding questions of the COVID-19 outbreak: what role did the market play in the outbreak – if any – and how did the virus get there in the first place?

The WHO has already admitted that despite ongoing research “very little is currently known about how, where and when the virus started circulation in Wuhan,” according to the terms of reference but a lack of preliminary data from the early days of the outbreak, including the type and number of animals sold in Huanan as well as the travel history and other exposure factors of the people who worked and shopped there might make it a difficult question to answer.

It is still unclear if the market was a “contamination source, acted as an amplifier for human-to-human transmission, or a combination of those factors,” WHO said in the terms of reference.

Much of the challenge comes from the fact that much of the evidence was lost when health authorities sealed the market off and disposed of what was there, leaving little for the first scientists who travelled to the city when the outbreak was first reported.

Whether the absence of data was deliberate is also unknown, although University of Hong Kong microbiologist Yuen Kwok-yung, told broadcaster the BBC in July there was “nothing to see” when he and other researchers went there in mid-January as part of an exploratory mission for China’s National Health Commission. The market had been cleaned up like a “crime scene”, he said.

While the market’s role in the worst pandemic in a century remains unclear, more progress has been made in answering questions about when COVID-19 first emerged in humans.

A crucial study published in medical journal The Lancet earlier this year and another by the University College London speculate the disease appeared in the last quarter of 2019, while government data obtained by the South China Morning Post newspaper reportedly showed Patient Zero may have been a man living in the same province as Wuhan whose symptoms emerged as early as November 17.

“It was estimated that probably the first human cases probably occurred some time in late October or early to mid November,” Rasmussen said. “That was after the study in February in the Lancet that showed that the first case that was definitely identified was December 1 and it was a person who had no connection to the Wuhan seafood market. The seafood market was super-spreading event, but it wasn’t the event that caused the virus to jump over from animals into people that probably happened before that.”

Bats without borders

While the Wuhan jump remains a mystery, researchers have circumstantial and evolutionary data about how the virus may have made its way to humans.

Besides seafood, Wuhan’s seafood market was also known to have 10 vendors trading in exotic wildlife species, many of which are still used in Chinese medicine and eaten as delicacies, according to the WHO’s terms of reference.

A number of animals have been cited by WHO as a possible source of the virus including the Malayan pangolin (also known as the Sunda pangolin) – a critically endangered species that is heavily trafficked in China – after a virus “92.4 percent homology to SARS-CoV-2” was found in the species, according to a study published in Nature journal in July.

The new study will consider the virus’ connection to bats in addition to other species, including farmed animals, as seen most recently in the speed with which COVID-19 spread through European mink populations, prompting Denmark to cull 17 million mink in October and November.

But while such animals may have been a stepping stone in the virus’s jump to humans, bats are widely regarded as the original reservoir, as they are well-established vectors for coronaviruses from SARS to the common cold, says Columbia’s Rasmussen.

“The genomic evidence suggests that this virus, like every other beta coronavirus that has emerged over the past 20 years including SARS classic and MERS (Middle East Respiratory Syndrome), appears to have come from a bat. There is no indication that it was engineered. There’s no evidence either that it was the result of a laboratory accident or research,” she said.

The first SARS virus that emerged 20 years ago in Guangdong was ultimately traced by Chinese scientists in 2017 to a group of horseshoe bats in a single cave in southwest China’s Yunnan Province.  The “spillover” event into humans may have occurred when humans interacted with the bats, perhaps gathering bat guano for fertiliser or similar activities.

Other research suggests it may have jumped to humans via civet cats, but bats were nevertheless the original host. Virologists now think a similar scenario may have happened in Wuhan’s market, which in the middle of winter provided excellent conditions for a virus to spread.

And this is where there is still a question mark, says Peter Daszak, a zoologist and one of the 10 international experts involved in the WHO research. Daszak was also a co-author of a leading international study with scientists in Wuhan that investigated Chinese horseshoes bats as a possible reservoir of COVID-19.

These kinds of bats are not known to travel far from their caves, which can be found across southern China thanks to its limestone landscape, Daszak said, but he was also careful to note that this landscape extends across the border into countries like Myanmar and Laos.

“The truth is we only sampled bats in China for that study, we didn’t really go into the countries on the border so it gives it a bit of a false view of the region. Of the hundreds of genetic sequences we got, you can analyse from those viruses and it looks like southwest China, Yunnan Province is one of the outposts,” Daszak said. “Guangdong is another hotspot too. We didn’t sample Vietnam, Myanmar, Laos … It could be the ancestors of SARS COVID-2 [COVID-19] could be in those countries, we just don’t know.”

He said that the virus could have been circulating for some time outside of Wuhan but it was undiscovered due to a somewhat weak public health sector.

“If this began in rural China, there’s less chance of this outbreak getting diagnosed. It’s possible it could’ve been put down as a pneumonia outbreak, even more so if it emerged over the border in Myanmar where the GDP [gross domestic product] per capita is even lower,” Dazak said. “The minute viruses like this get into cities there is better chance of them being identified. Wuhan is the place where they found the first evidence but it may have started somewhere else.”

Propaganda chatter

 

But as scientists prepare to head to China, with signs still pointing to Wuhan as the first chief virus cluster, Chinese state media continues to construct an alternative narrative, often cherry-picking data from global studies that appear to support their case.

On November 16, state news agency Xinhua picked up a study published by the Tumori Journal, the publication of the Milan’s National Cancer Institute, that pointed to an Italian screening of lung cancer patients that found coronavirus antibodies in late 2019.

Another article from the Global Times, a state-run tabloid, on December 2 suggested the possible presence of the coronavirus in the United States before it emerged in Wuhan, while further confusion has been made from studies like an analysis of wastewater in Spain that suggested COVID-19 may have been present as early as March 2019.

Frozen food has also been cited by state media as yet another possible way the virus entered China after the external packaging of imported products was found to have traces of COVID-19. The theory has even been touted by Dr Wu Zunyou, the chief epidemiologist at the Chinese Center for Disease Control and Prevention, according to the Global Times.

Such studies, however, have done little to challenge the mainstream scientific community’s views, points out Claire Standley, an assistant research professor at Georgetown University’s Center for Global Health Science and Security.

The reason, she says, is that many of the studies are based on serological testing, which looks for virus antibodies. These kinds of tests can cross-react with other coronavirus antibodies, such as those from the common cold, which makes them less reliable than DNA-based testing.

“There are two things to look at: technique to look at and the extent to which it is supported by other pieces of evidence,” Standley said. “Any kind of test that looks for genetic material specific to SARS-CoV-2 is going to be better than a test that looks for antibodies.”

A serological study of US blood bank samples in nine states published late last month suggested COVID-19 may have been spreading in the US in December after antibodies were found in 2 percent of samples, Standley notes, but the findings were not supported by clinical evidence.

If 2 percent of the population had had coronavirus at that time, she says there would have been substantially more clinical evidence in the form of thousands of people falling ill at the same time. The same would probably have been true for Spain and Italy if the virus were really present in the kinds of numbers needed to prove COVID-19 emerged there.

While Standley says while low-level transmission might have occurred in some European cities in late December, China remains the most likely source of the virus.

“Until there is evidence, I think that China is the most likely origin,” she said. “We know the bats that this virus is most likely to have come from are predominant around central and southern China, until we have compelling evidence to the contrary, the epidemiological evidence shows that people were infected in China in November and that has not been seen elsewhere.”