Where did COVID come from?

 Where did COVID come from? Five mysteries that remain

In the wake of the World Health Organization’s investigation, there are nonetheless key questions about when, the place and how the pandemic began.

Following a month-long fact-finding mission in China, a World Health Organization (WHO) group investigating the origins of the COVID-19 pandemic concluded that the virus probable originated in bats and exceeded to humans via an intermediate animal. But imperative questions continue to be about when, the place and how SARS-CoV-2 first contaminated people.

As the worldwide WHO crew finalizes a file of its findings, which is predicted subsequent week, Nature speaks to 4 of the investigators about what they nevertheless desire to know.

Was the virus circulating in Wuhan earlier than the first recognized cases?

To hint the virus’s origin, it’s integral to pin down precisely when the first instances befell in people. The WHO group mounted that the first character recognized to have COVID-19 was once an workplace employee in Wuhan with no current journey history, who commenced displaying signs on eight December 2019, says Peter Ben Embarek, a food-safety scientist at the WHO in Geneva, Switzerland, who led the investigation. But the virus was once probable spreading in the town earlier than that, due to the fact it used to be well-established through later that month, he says.

Yet proof of until now unfold has proved elusive. Researchers in China carried out an significant survey of affected person reviews from hospitals in Wuhan made between October and December 2019, and recognized fewer than one hundred humans who had signs and symptoms of COVID-19. They then examined the blood of sixty seven of these human beings for antibodies generated with the aid of previous contamination with SARS-CoV-2, however observed none. This suggests there wasn’t a massive cluster of infections earlier than December, or an uncommon spike in deaths in the surrounding province of Hubei

But Ben Embarek says the evaluation have to be repeated the usage of much less restrictive symptom criteria, to make certain that researchers spot all possible COVID-19 cases.

Scientists in China have to additionally search for proof of previous contamination in some 200,000 archived samples presently held at the Wuhan Blood Center and in different areas throughout China, says crew member Dominic Dwyer, a clinical virologist at New South Wales Health Pathology in Sydney, Australia. This would exhibit whether or not the virus used to be spreading in the conventional populace in China — now not simply amongst human beings who went to fitness amenities — earlier than December 2019.

Some scientists now not worried in the WHO investigation have already appeared at blood-bank samples taken up to a yr earlier than the pandemic, in Guangzhou, southern China. (Close household of SARS-CoV-2 have been determined in bats and pangolins in southern China.) Some of the samples examined fantastic for antibodies towards SARS-CoV-2, however Ian Lipkin, an infectious-diseases researcher at Columbia University in New York City, who labored on the analysis, says the check was once no longer unique sufficient to say for certain that the antibodies weren’t triggered with the aid of contamination with different viruses. “There is a lot of laboratory work that wishes to be performed that hasn’t been done,” says Lipkin, who additionally wishes to recognize whether or not there are post-mortem samples from earlier than December 2019 that may want to be studied for traces of viral genetic material.

Was the virus spreading in humans backyard China earlier than December 2019?

Answering this query is also key to organising the timeline of the first COVID-19 cases. Previously, researchers in Europe have reported1,2,3 discovering antibodies in opposition to SARS-CoV-2 in samples taken at blood banks from November 2019 onwards.

Ben Embarek says this doesn’t always advise the virus originated in Europe, however helps the concept that it used to be spreading in Wuhan earlier than the first recognised cases. “Wuhan at that time was once a very well-connected worldwide town with direct flights to the whole planet on a each day basis. So if it used to be circulating in Wuhan, it may want to without problems have been introduced to different components of the world thru travellers, and circulating again, undetected, in special regions,” he says.

Still, he recommends that the blood samples from Europe be retested to verify that they point out instances of COVID-19. Some of them, from Italy and France, are already being reanalysed, he says.

What was once the function of the Huanan market?

The intermediate animal that exceeded the virus from bats to human beings has no longer been identified, however researchers assume it may be a wild species that is offered as meals in ‘wet markets’, which normally promote stay animals. Early in the pandemic, investigators homed in on the Huanan Seafood Market in Wuhan, due to the fact it bought clean and frozen animals and many of the earliest infections had been in human beings who had visited it. But the lead went bloodless when different early instances have been observed that had been now not related with the market. Viral cloth used to be recognized in drains and sewage at the market, however none was once discovered on any animal carcasses.

Still, the market is the solely area the place a giant wide variety of the human beings contaminated at the begin of the outbreak have been uncovered to meat and animals. It’s necessary to set up how the virus bought into the market and whether or not it was once on an animal, says WHO group member Hung Nguyen-Viet, an surroundings and food-safety researcher at the International Livestock Research Institute in Nairobi.

Nguyen-Viet says the crew recognized ten stalls promoting wildlife, both wild or farmed, that may want to have carried the virus into the market from farms in southern China. Some wild animals offered for meat, such as rabbits and ferret-badgers, are prone to SARS-CoV-2 or the associated virus that reasons extreme acute respiratory syndrome (SARS).

WHO crew member Peter Daszak, president of the non-profit lookup organisation Ecohealth Alliance in New York City, says the farms ought to be investigated to see whether or not there have been infections in the animals or amongst workers. He additionally needs to recognize what animals had been bought in different Wuhan markets. When the group interviewed the first man or woman regarded to have COVID-19, he cited that his dad and mom had visited a neighborhood neighborhood moist market, says Daszak.

Did frozen wild-animal meat have a function in the early unfold of the virus?

The WHO crew concluded that it’s most probable the virus jumped from stay animals to people, however Ben Embarek says it is feasible the virus entered the Huanan market thru contaminated frozen wild animals from farms in southern China, and then sparked an outbreak. Daszak wonders whether or not frozen ferret-badgers offered at the market should have carried the virus. “These had been carcasses skinned at the market, now not simply cubes of meat in a plastic packet,” he says.

Although researchers in China have additionally isolated viral RNA from the packaging of imported frozen fish4, Ben Embarek says the WHO crew concluded that these items have been now not probable to be the route of the virus’s first arrival in Wuhan.

Lipkin says there is no proof that the virus entered the market thru contaminated frozen wild animals. It ought to have simply as effortlessly been introduced in via contaminated human beings who treated wild animals, he says.

Was the virus circulating in animals in China earlier than the pandemic?

To set up which animal surpassed the virus to people, researchers want to locate proof of the virus in that species. Researchers in China examined some 30,000 wild, farmed and home animals in 2019 and 2020 however discovered no proof of energetic or previous SARS-CoV-2 infection, besides in some cats in Wuhan in March 20205.

However, Ben Embarek says these surveys had been no longer consultant of China’s ordinary animal population, and that many extra animals want to be examined for traces of infection, specially on natural world farms. “The quantity of trying out that’s been achieved is no longer adequate to say, in any way, that natural world farms had been now not carrying the virus,” says Daszak.

The explosive way in which the outbreak took off in Wuhan in December suggests that the virus was once likely delivered once, via the flora and fauna trade, says Daszak. He says future trying out have to focal point on farmed wild animals.