On December 31 2019, as the world paused to raise a glass to the end of a tumultuous decade, three paragraphs of text revealed that 27 people had been struck down with a “pneumonia of unknown cause” in central China.
Published without fanfare by the Wuhan Municipal Health Commission, this statement announced to the world the presence of a virus that would be later named Sars-Cov-2.
Six months later and that virus has killed almost 570,000 people, infected some 13 million and led to unprecedented lockdowns across the globe.
But experts are still wrestling with a key question - where did it come from?
To answer that, the World Health Organization has sent a two person “scoping missing” to China, which aims to establish a methodology for tracing the origins of Sars-Cov-2.
“Knowing the source of the virus is very, very important,” said Dr Tedros Adhanom Ghebreyesus, director general of the WHO, as he announced the initiative at the start of July. “We can fight the virus better when we know everything about the virus, including how it started.”
The team is unlikely to come back with all the answers - such disease detective work is notoriously difficult and could take years. It is now more than four decades since Ebola first emerged but the source remains unproven.
But experts have welcomed the WHO’s scouting mission as a starting point to understand the research already done and determine the gaps for a broader investigation.
Though the Wuhan Health Commission initially indicated that the outbreak was linked to a cluster of cases at the Huanan Seafood Market, early epidemiological studies found that four of the first five confirmed cases had no connection to the wet market.
Since then various theories have flourished - including the idea that the virus was modified or escaped from a laboratory at the Wuhan Institute of Virology (WIV), where China’s famous “batwoman” Shi Zheng-Li leads global research on bat coronaviruses.
These theories have been discounted by most virologists and evolutionary biologists, who instead suggest that bats in southern China are the most likely source of Sars-Cov-2.
To reach an irrefutable conclusion, though, rigorous analysis is needed - particularly around which animal acted as a bridge between bats and humans.
“If done well scientifically, then this investigation should allay persistent concerns about the origin of this virus… [and] help build global solidarity against the pandemic moving forward,” Dr Daniel Lucey, an infectious disease specialist at Georgetown University, wrote in a much shared blogpost on the investigation for the Infectious Diseases Society of America.
“It could also help set an improved standard for investigating and stopping the awful viruses, and other pathogens, in the decades ahead that will originate from different parts of the world,” he added.
With all this in mind, here are just some of the key questions observers hope any investigation into the emergence of Sars-Cov-2 will address - and why:
1. What did researchers find during the early studies in the Huanan Seafood Market?
Understanding which animals were tested - and which came back positive - in these epidemiological studies could help ascertain the initial chain of transmission. During the 2002 to 2003 Sars outbreak, extensive sampling of animals in markets in China’s Guangdong province led to the discovery that the virus came from palm civets.
Wildlife and farm animals are not the only potential route of transmission. Prof Shi’s research team at WIV have already done a study of feral and domesticated cats in Wuhan and found Sars-Cov-2 antibodies in 15 per cent of 141 samples tested. Are there more samples stored by vets that could help indicate if the virus was circulating pre-December? Could pet cats have taken the virus from wet markets home to their owners?
We also know that there were more than 500 “environmental samples” taken at the market in early January, and 33 tested positive. But what were they? Rubbish? Door handles? Cutting boards? And did they have any link to the first human infections?
2. Were other markets tested within Wuhan, the wider Hubei province, and other parts of China?
Dr Peter Daszak, President of the EcoHealth alliance and a well known virus hunter, told the Telegraph that the role of the wildlife trade has likely been “underestimated” during the pandemic.
So have samples from animals known to be susceptible to diseases - including mink, raccoon dogs, civet cats and ferrets - been tested more broadly to determine a possible route for the virus? What species of pangolin, which were initially considered an intermediary between bats and humans, were tested?
Dr Maria Van Kerkhove, head of the WHO's emerging diseases unit, has said this bit of information is crucial because “knowing what the intermediary host is will help us prevent this again”.
Also importantly, how far back in time have samples been probed? Have researchers aggressively sought out the virus in the period before the first known cases in Wuhan, or elsewhere? There’s no reason to believe that the virus came from the city, even though that was where the first cases were recorded.
3. Has all of the data about the first patients been made public?
While China has made a great deal of data available, and the first WHO mission to the country in February uncovered even more, there are still questions about the movements and behaviour of those infected right at the beginning.
Where had these people been in the weeks before falling ill? Which animals had they come into contact with? Were their contacts tested at the time - and have they had antibody tests since? And how did the patients themselves come into contact with each other? Could they have come into direct contact with bats?
4. Do Chinese authorities have additional information about potential Sars-Cov-2 infections that predate December 2019?
In his blog post Dr Lucey points to a detailed article in The South China Morning Post, which said it had seen "government data" identifying an early human coronavirus case on November 17 in Hubei. The report says eight other cases have been found that month.
So where in Hubei province were each of these cases reported? Were there additional cases documented or suspected before November 17? Could this point to more links with the wildlife trade, as Dr Daszak suspects?
5. Can widespread screening of people, wildlife, farmed animals and domestic pets be done to help trace the origins? And do stored samples already exist?
Again, this will be key to understand the trajectory of the outbreak. The sampling of chimpanzee facces in sub Saharan Africa has been crucial to our understanding of the origins of HIV. And researchers have traced the H1N1 flu pandemic to infected pigs that were reared in farms in Mexico.
7. What about sewage?
Recently, researchers in Barcelona published a preprint study (that has not been peer reviewed) suggesting that Sars-Cov-2 was found in sewage samples dating back to March 2019. This seems unlikely but the principle still holds, and this method is used to track diseases including polio.
Similar studies in Italy detected the virus in December 2019, while some experts have suggested that samples from water systems could be used as an early warning system for potential flare ups. Are there samples in Wuhan that could be tested?
8. What research was being conducted at WIV - and how were experiments conducted?
Dr Lucey said that any investigation of the origins of Covid-19 cannot shy away from this area, even though there is currently no evidence to support theories that the virus escaped from the lab or was modified.
But experts say the WHO team should ask what type of research was being done on coronavirus at WIV - for instance, were controversial "gain-of-function studies" conducted? Here, researchers engineer viruses to make them more transmissible between humans to better understand how they work and how to prevent pandemics. But critics have warned they could trigger accidental leaks.
It’s also not currently known which bat coronaviruses were being stored at the institute and whether any of them can infect humans.
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