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Illustration: Lau Ka-kuen

Coronavirus: Covid-19 scientists seek the invisible in Wuhan investigation into deadly pathogen

  • Researchers from around the world will join Chinese scientists in the hunt for the origins of the virus ‘as soon as possible’, World Health Organization says
  • Phase one will begin in the central China city where the pandemic began and include the search for ‘patient zero’

This is the second article in a series on the Covid-19 disease, one year after it first emerged in the Chinese city of Wuhan. It explores the response to the pandemic and what lessons may be learned as medical science predicts it won’t be the last. Please support us on our mission to bring you quality journalism.

Uncovering how a new virus made its first microscopic leap into a human body is challenging work for scientists at the best of times. One year after a viral outbreak that turned global pandemic, sickening millions and inflaming political feuds, is not the best of times.

But the World Health Organization’s much anticipated mission to uncover the origins of the virus behind Covid-19 is going ahead, with a research plan and 10 international experts selected for the team.

They will join Chinese scientists working on the ground in Wuhan, the original epicentre of the outbreak, “as soon as possible”, according to the WHO.

The researchers – from Europe, the United States, Japan, Vietnam, Australia, Russia and Qatar – and their Chinese counterparts are stepping into a political quagmire. The US has blamed China for the outbreak, while Beijing has countered that the virus could have emerged elsewhere and merely been detected in Wuhan.

At a United Nations meeting this month, US Health and Human Services Secretary Alex Azar said “the key issue is not where the virus first appeared, it is whether information about the virus was shared in a timely and transparent way”, a reference to Washington’s complaints about China’s early handling of the outbreak.

Over a year has passed since the virus first sickened people in Wuhan. That leaves questions about the likelihood of finding new evidence on its origin or adding to work China has said its scientists have already done, but about which few details have been made public.

Explainer | Coronavirus: the hunt for ‘patient zero’ – and why the world’s health may depend on it

Yet pulling off the mission has become critical for the embattled WHO, which lost the support of the US earlier this year as the Trump administration said the UN body was under the sway of China.

“Our position is we want to know the origin and we will do everything to know the origin. You don’t need to have any confusion on this,” WHO director general Tedros Ghebreyesus said at the end of last month.

“It will help us to prevent future outbreaks,” he said.

Phase one: the hunt for patient zero

When the central Chinese city of Wuhan put out the alarm about a mysterious pneumonia on the afternoon of December 31, health authorities had already linked over two dozen patients to a sprawling wet market that sold seafood, meat and wildlife.

The connection to the Huanan Seafood Wholesale Market had echoes of China’s outbreak of severe acute respiratory syndrome (Sars) nearly 20 years earlier. Then, a pneumonia-causing coronavirus likely jumped to people from infected civet cats in similar wet markets in the south of the country.

Scientists broadly agree that this new virus, like some 70 per cent of pathogens discovered over the past 50 years, also comes from an animal, probably a bat. The belief is the virus may have entered first into an intermediary animal, from which it spread to humans.

But where that happened remains unknown, as no hard evidence has been put forward linking an infected animal to the market – or to anywhere else.

Low-hanging fruit will have been picked up a long, long time ago by Chinese scientists, so it’s not going to be straightforward for the international team to find something new.
Linfa Wang, professor of emerging infectious diseases at Duke-NUS Medical School in Singapore

Into the uncertainty has since come a deluge of conspiracy theories, such as the pathogen was engineered at a Wuhan lab studying coronaviruses or planted in the city by the US military.

More recently, Chinese epidemiologists have suggested without evidence that it came from overseas, carried into the market on imported goods.

Amid the whirr of speculation, making sense of how the virus broke out in Wuhan is at the centre of the WHO mission’s “phase one” studies, outlined in a so-called terms of reference document released in November.

Phase one begins in the city and includes the hunt for a “patient zero”. This includes scouring hospital records for early cases that might have been missed, testing stored blood samples, and interviewing the earliest patients to understand risk factors, like wild animal contact.

Researchers will also hunt animal sources through the market, mapping supply chains and developing a strategy for testing more animals. Chinese researchers will start the work and the international team is expected to join them to review the phase one findings, according to the WHO.

“One thing that has to be clear is the study will start from Wuhan in China, where the first report came from, and then from there, based on the findings, we can go anywhere,” Tedros said last month.

Finding the missing link

What the mission accomplishes in China will depend on more than just the science, according to Linfa Wang, a professor of emerging infectious diseases at Duke-NUS Medical School in Singapore.

“A mission like that can only work if the Chinese are thinking that you’re coming here without political motivation,” said Wang, who was part of the WHO team that investigated the Sars outbreak in China 17 years ago.

“Low-hanging fruit will have been picked up a long, long time ago by Chinese scientists, so it’s not going to be straightforward for the international team to find something new,” he said.

Understanding what research China had already done was key to planning the first phase of the WHO mission, the Geneva-based organisation said earlier this year.

Not much is publicly known about the extent of China’s research to find earlier patients or infected animals, but officials have said none of the potential host animals tested so far have been positive for the virus, known as SARS-CoV-2.

“For some other viruses, it’s so easy to find the intermediary host,” Gao Fu, director of the Chinese Centre for Disease Control and Prevention, said at a scientific conference last month. “Yet we tried so hard and we haven’t found anything for Covid-19.”

If you go to a farm with 10,000 civets or mink, the virus could have gone into the farm a year ago, spread through and moved on.
Disease ecologist Peter Daszak

Scientists typically employ several tools to find whether animals may have played a role in an outbreak.

One is testing them for active infection, another is looking for traces of past infection in their blood, a method known as serology that is less precise, but where evidence is longer-lasting.

But even with these tools, scientists need to be looking “in the right place at the right time”, according to disease ecologist Peter Daszak, one of the scientists on the WHO mission. He has conducted research into bat coronaviruses in China for nearly two decades.

Disease ecologist Peter Daszak has been conducting research into bat coronaviruses in China for nearly two decades. Photo: Twitter

He points to China’s wildlife breeding farms as an obvious place for scientists to investigate.

“If you go to a farm with 10,000 civets or mink, the virus could have gone into the farm a year ago, spread through and moved on,” said Daszak, who is president of the US research body EcoHealth Alliance. “You’re not going to see any evidence of it,” he said.

Could a cave be key?

The current best clue as to where the virus that causes Covid-19 came from was found in 2013 in a cave in China’s subtropical southwestern province of Yunnan.

There, researchers collected genetic material from a virus found in a bat that would later prove to be 96 per cent similar to SARS-CoV-2. It is the closest relative so far discovered, but still distant in evolutionary terms.

Researchers had been drawn to the region’s caves while looking for the so-called progenitor, or parent, pathogen that caused the Sars outbreak. Years after that outbreak and over a thousand miles from where it began, scientists found a live virus with a 95 per cent match to the human version. But that breakthrough did not provide the genetic similarity needed to say it was the direct Sars ancestor.

“Right now people are complaining about the slowness in finding the origin of Sars 2. Come on, 17 years later we still haven’t found that progenitor virus for Sars 1,” said Wang, who with Daszak, was involved in the research.

Getting to a point of certainty on the source animal means finding a virus more than 99 per cent similar across the whole genome and is “needle in a haystack stuff”, according to evolutionary biologist Edward Holmes, a professor at the University of Sydney in Australia.

“[This] may come down to looking in one specific population. For example, it could mean sampling a particular bat in a particular cave at a particular time,” he said.

But the more genetic data that is available from related coronaviruses, the better scientists will be able to narrow down where to look, according to genomic scientist Tommy Lam, an assistant professor at the University of Hong Kong’s School of Public Health.

China’s ‘bat woman’ virologist rules out Covid-19 virus in fresh tests on old cave samples

Researchers across Asia have been digging back into their laboratory freezers with this in mind, and a Cambodian group turned up what appeared to be a closely related bat coronavirus, the science journal Nature reported last month.

The geographic range of samples and how the genetic information fit into the SARS-CoV-2 family tree “may point to the potential original place where the virus jumped to the intermediate host or jumped to humans”, Lam said.

Global tracing ‘could take years’

But where that jump happened is no longer just a scientific question, but a matter of politics.

China’s diplomats, state media and scientists have suggested the virus may not have come from China, and Beijing has couched its cooperation with the WHO mission in such terms. The mission includes no reference to questions raised by the US about investigating the possibility the virus escaped from a lab, but does mention the need to “clarify” transmission via food, a nod to controversial claims by Chinese scientists that the virus has spread from imported food packaging.

“Origin tracing is an ongoing process that may involve many countries. We hope that all countries will adopt a positive attitude and strengthen cooperation with the WHO,” China’s foreign ministry spokesman Zhao Lijian said last month.

To be sure, the WHO has said the mission will need to follow the science, wherever it may lead.

And there have been unexpected findings, including genetic evidence of an infected child in Italy in December 2019 and a Covid-19 positive man in France the same month, indicating the virus was spreading earlier than thought.

The WHO has said it is tracking these reports and scientists agree the more data, the better.

Duke-NUS’s Wang said “without any doubt, scientifically” more countries should be reaching back to test stored samples from hospital patients and animals to understand if this virus or similar ones were circulating earlier than known or in unexpected places.

China to have 600 million doses of Covid-19 vaccines ‘ready for market this year’

But so far the genetic clues acquired over years of global research on bat viruses in different regions point to SARS-CoV-2 emerging in China or southern Asia, experts say.

“The evidence that we are seeing from wildlife says that writ large Southeast Asia, China is a hotspot for this group of viruses,” said Daszak, noting as other researchers have, that this means the virus could have spilled over from animals in one of China’s neighbouring countries.

As the WHO mission pursues the search, one essential the organisation and scientists stress is patience.

“It could take years to resolve origins. Indeed, looking at the bigger picture there are actually very few human viruses where we definitely know the animal reservoir,” said University of Sydney’s Holmes.

“Our only option is to keep looking.”

The third story in the series will take a closer look at the Wuhan market, using a never-before-published floor plan of the sprawling facility used by the early investigators in China.

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