1. Why don’t we know where it came from?
Where, when and how a pathogen crosses the species barrier and begins spreading in humans can be difficult, if not impossible, to pinpoint. Although SARS-CoV-2 is genetically similar to coronaviruses collected from a type of bat, it may have followed a long and convoluted path to Wuhan, a city of 11 million people. Scientists are tracing the earliest known cases to try to establish how they were infected, but the trail backward largely goes cold in early December 2019. Where a new disease starts spreading isn’t necessarily where it spilled over from the animal kingdom to infect the first human. HIV, for instance, is thought to have originated in chimpanzees in southeastern Cameroon, but didn’t begin spreading readily in people until the 1920s, when it reached the city of Kinshasa, hundreds of miles away. Scientists reported that finding in 2014, some three decades after the AIDS pandemic was recognized.
The World Health Organization was asked in May to help with the research, and a team of 17 international scientists, including one based in the U.S., concluded a four-week joint mission with 17 researchers from China in early February. Their findings are slated to be released in March. Other groups, including an expert panel convened by the medical journal The Lancet called the Covid-19 Commission, are also probing the virus’s origins.
3. What do we know so far?
Not much. Bats are the source of two coronaviruses that caused lethal outbreaks in people during the past two decades — severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) — and the flying mammals are considered the reservoir host for SARS-CoV-2 as well as a plethora of other viruses. (A reservoir host is an animal that harbors a pathogen but isn’t sickened by it.) After SARS-CoV-2 emerged, Shi Zhengli, a virologist who heads a group that studies bat-borne coronaviruses at the Wuhan Institute of Virology, identified three closely related viruses collected during the previous 15 years. The closest, which is about 96% identical to SARS-CoV-2, was isolated from swabs and fecal material from Rhinolophus affinis, a species of horseshoe bat, in the southern Chinese province of Yunnan in 2013. Some researchers have linked that particular virus to a mineshaft in Mojiang county in Yunnan, where six men contracted a pneumonia-like disease in 2012 that killed three of them. Although SARS-CoV-2 and the virus from Yunnan may share a common ancestor, they’re not sufficiently similar to indicate SARS-CoV-2 was derived from the Yunnan virus. Sampling of bats in Hubei, the province of which Wuhan is the capital, haven’t found any positive for the pandemic strain. Coronaviruses sharing certain genetic features with SARS-CoV-2 have been found in other Rhinolophus bat species and pangolins, a scaly, ant-eating mammal, elsewhere in Asia, highlighting the broad distribution of related coronaviruses that may have contributed to SARS-CoV-2’s evolution. That’s led to multiple hypotheses for how and where it emerged.
4. What are the hypotheses?
Scientists involved in the WHO-led mission identified four main ones:
• the virus spilled over to humans directly from an animal reservoir;
• the virus spilled over via an “intermediary” host species in which it may have undergone some adaptation, making it better suited to infecting humans and spreading from person to person;
• the virus was introduced via the food chain by contaminated food or packaging;
• the virus emerged as a result of a laboratory-related accident.
Their initial findings suggest that an intermediary host species is the most likely pathway. Since no such animal or animals have so far been found, they said more research is required, including into the potential role that the trade in animals, animal products and frozen or refrigerated products might have played.
5. What’s known about the earliest Covid-19 cases?
The WHO mission found no evidence of widespread SARS-CoV-2 circulation in Wuhan before December 2019. Among the earliest cases, symptoms began on Dec. 8. That suggests infections probably occurred around the start of December or late November. It’s possible the virus was transmitted multiple times and went extinct when infected individuals didn’t transmit the virus to anyone, according to researchers at the University of California, San Diego. Eventually, the virus infected someone who passed it to several people, who also passed it on to others, possibly in a super-spreading event. The researchers studied SARS-CoV-2 virus genomes and the pace at which they mutated and diversified from the earliest known specimens in Wuhan. From mid-October to mid-November 2019 is the most plausible period in which the first case of a person contracting SARS-CoV-2 emerged in Hubei province, they wrote in a March 18 paper in Science. How those people became infected, though, remains a mystery.
6. What role did the food market play?
Researchers aren’t sure. It could have acted as a contamination source, an amplifier for human-to-human transmission, or both. A cluster of cases of pneumonia-like illness was identified among people who worked at, or had visited, the Huanan seafood market in downtown Wuhan. The so-called wet market had 653 stalls and more than 1,180 employees supplying seafood products as well as fresh fruit and vegetables, meat, and live animals before it closed on Jan. 1, 2020. Days before, 10 stall operators were trading live wild animals, including chipmunks, foxes, raccoons, wild boar, giant salamanders, hedgehogs, sika deer. Farmed, wild and domestic animals were also traded at the market including snakes, frogs, quails, bamboo rats, rabbits, crocodiles and badgers. Of Covid-19 cases linked to the market, the first became unwell on Dec. 12, 2019. Still, since the first known Covid-19 case preceded that by four days, it’s possible that SARS-CoV-2 was introduced to the market by an already infected person — potentially a trader or a visitor not showing symptoms — who passed it to others in a super-spreading event. Testing after the market was shut down that month found widespread contamination of surfaces compatible with SARS-CoV-2 being introduced through infected people, live animals, or tainted animal products or refrigerated items. Supply chains to the market were extensive, with goods arriving from other countries and various parts of China. Of the 336 samples collected from animals, none were positive for SARS-CoV-2, but it’s possible that not enough samples were taken.
7. Were there cases elsewhere?
Yes. Some early cases occurred among individuals who were linked to other markets in Wuhan and some had no market links. In addition, genetic sequencing of viral specimens collected from patients early in the pandemic showed there was some diversity already present, suggesting SARS-CoV-2 was more broadly distributed in the city.
8. Could the virus have been introduced via contaminated food?
There’s disagreement on this. Researchers in China have found that SARS-CoV-2 can persist in conditions found in frozen food and packaging and cold-chain products, which are kept refrigerated throughout the supply chain. They also have linked some infections in people to imported goods, although the degree of surface contact or amount of virus required is unknown. China’s government has embraced this theory and has been testing imported food for virus traces for months; some supermarkets even have separate coolers for imported goods. The U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention said in February, however, that there is no credible evidence of food or food packaging associated with, or as a likely source, of SARS-CoV-2 transmission. Covid-19 outbreaks did occur in 2020 in meat-processing plants and some preparing ready-made meals, making it plausible that infected workers could contaminate items they’re in contact with. The WHO mission chief called the theory “worth exploring,” but pointed out that in 2019, “there were no widespread outbreaks of Covid-19 in food factories around the world.”
9. What about the lab theory?
After meetings with scientists in Wuhan, including discussions about their bio-containment and safety practices, the WHO mission found it extremely unlikely that SARS-CoV-2 originated in one of several laboratories in the city conducting research on coronaviruses, a large family that includes viruses that cause the common cold as well as SARS-CoV-2. Although lab accidents have been known to occur, sparking rare outbreaks, the scientists noted that there had been no reports of the virus existing before it was detected in Wuhan. Researchers who have analyzed the sequence of SARS-CoV-2 have concluded that it doesn’t have the genetic signatures of a lab-engineered virus. Also labs in Wuhan retrospectively tested their staff and students for evidence of SARS-CoV-2 infection and found no cases.
10. What’s considered more likely then?
Some vendors at the Huanan market were trading in farmed animals including ferret-badgers, bamboo rats and rabbits that are susceptible to coronaviruses, and some were supplied by traders and farms in areas where coronaviruses are carried by bats. Potentially, some were infected before being brought to market. The WHO mission said further research should involve tracing these products to their source and testing other animals there, as well as their surroundings and people living nearby. Wild animal markets were linked to the emergence of SARS in China’s Guangdong province in 2002.
11. What research has been undertaken?
To identify the earliest human cases, the team reviewed health records, mortality data, trends in retail sales of cold and cough medications and reported patterns of influenza-like illnesses and severe respiratory infections in the two months preceding the outbreak in Wuhan. Included were 76,000 cases from more than 200 medical centers. Researchers in China also tested some 4,500 patient specimens stored at hospitals in Wuhan and others parts of China for SARS-CoV-2, and analyzed blood samples for antibodies against the virus. To identify potential animal sources, 11,000 blood samples taken from livestock and poultry in 31 provinces were tested along with 1,914 samples from 35 different species of wild animals. Researchers in China looked for SARS-CoV-2 in 12,000 animal swabs and 50,000 samples from 300 different species of wild animals. All were negative.
12. Did the WHO team get to see everything?
The Australian Broadcasting Corp., citing one of the international experts, reported that dozens of people were hospitalized as early as October 2019 with symptoms such as fever and coughing, but Chinese authorities refused to make available raw data on the cases because of patient privacy concerns. Chinese experts said they had found no trace of Covid-19 among the cases, but the tests were incomplete and members of the WHO-led team said more research was needed, the New York Times reported. International experts are reported to have said that, while they had access to an unprecedented amount of data, it’s uncertain whether everything available was supplied.
13. Are the findings credible?
It’s hard to say. Studies have been hampered by delays and geopolitics. China’s government has supported the hypothesis that SARS-CoV-2 may have entered the country in imported food, while the former Trump administration repeatedly blamed Shi’s Wuhan lab for the “China virus,” which she has denied. All that has heightened the sensitivity of the WHO-led mission. Team members described discussions in Wuhan as very tense on occasion, sometimes erupting into shouts on both sides. Meetings were also closely monitored by dozens of Chinese representatives, a large number of whom weren’t scientists or public health officials. The WHO team is still pressing Chinese officials to conduct exhaustive tests on stored blood-donation samples from Wuhan in 2019, which might indicate whether the virus was present there earlier. Under President Joe Biden, the U.S. State Department in early February said “the jury is still out” on the level of transparency and cooperation the WHO team received from China.
In addition to further tracing of animals and products that might have been at the Huanan market, the WHO mission scientists propose:
• collecting and analyzing epidemiological, clinical, molecular and environmental data from other countries to better understand the virus’s origins, since some reports have suggested SARS-CoV-2 may have been circulating outside China before December 2019;
• additional sampling of animal species that may act as a reservoir for SARS-CoV-2, including bat populations in China and neighboring countries;
• more research to understand if SARS-CoV-2 could be transmitted from contaminated products to humans, and under which conditions that might occur;
• further analysis of cases of respiratory illness that occurred in Wuhan in October and November 2019.
(Updates to add estimated timing of virus emergence in section 5; additional details about Huanan market, including live animals sold there in section 6.)