Spyros Lytras, Wei Xia, Joseph Hughes, Xiaowei Jiang, David L
Although the virus was first detected in December 2019, it was inferred that COVID-19 was present in Hubei Province, China, for approximately one month prior.
Where did this new human disease come from?
To understand the origin of the COVID-19 pandemic, it is necessary to go back to 2002. At that time, a novel respiratory coronavirus emerged in Foshan, Guangdong Province, China, and spread to 29 countries. In total, approximately 8,000 people were infected with severe acute respiratory syndrome coronavirus (SARS-CoV) before public health measures brought its spread under control in 2003. The zoonotic origin of SARS-CoV was subsequently linked to live animals available in markets. In Guangzhou, Guangdong, further sporadic outbreaks of SARS-CoV from animals occurred, and some researchers working with cultured viruses were infected in laboratory accidents (3), but SARS-CoV was eventually eliminated from the human population. The trade in susceptible animal hosts is a significant common theme in the origins of both SARS and COVID-19.
Three years after the SARS epidemic began, research revealed that horseshoe bats (Rhinolophus) in China harbored related coronaviruses. These collectively form the SARS-related coronavirus (SARS-CoV) species, which comprises the subgenus sarbecovirus of the genus Betacoronavirus. It was inferred that a sarbecovirus circulating in horseshoe bats seeded the progenitor of SARS-CoV in an intermediate animal host, most likely civet cats. Although other potential intermediate hosts for SARS-CoV were identified, notably raccoon dogs and badgers (sold with civet cats in animal markets), it is a population of civet cats within the markets that appears to have acted as transmission conduits to humans from the horseshoe bat reservoir of SARS-CoV, rather than civet cats being a long-term reservoir host species. Presumably, a captive civet cat was initially infected through direct contact with bats, for example, as a result of bats foraging in farms or markets, or was infected before capture. After the SARS epidemic, increased surveillance revealed the immediate threat posed by sarbecoviruses from horseshoe bats. Despite this clear warning, another member of the SARSr-CoV species, SARS-CoV-2, emerged in 2019 and spread with unprecedented efficiency among humans. It has been speculated that the Wuhan Institute of Virology (WIV) in Hubei was the source of the pandemic because, to date, no intermediate host of SARS-CoV-2 has been identified due to WIV's geographic location.
SARS-CoV-2 first emerged in the city of Wuhan, which is 1500 km from the nearest known naturally occurring sarbecovirus collected from horseshoe bats in Yunnan Province, leading to an apparent puzzle: How did SARS-CoV-2 get to Wuhan? Since its emergence, sampling has revealed that coronaviruses genetically close to SARS-CoV-2 are circulating in horseshoe bats, which are widely dispersed from east to west across China, and in Southeast Asia and Japan. The broad geographic ranges of potential reservoir hosts, for example, intermediate (R. affinis) or lesser (R. pusillus) horseshoe bat species, which are known to be infected with sarbecoviruses, suggest that the singular focus on Yunnan is misplaced (5). Confirming this assertion, it is estimated that the closest evolutionary relatives of bat sarbecoviruses share a common ancestor with SARS-CoV-2 at least 40 years ago, demonstrating that these viruses collected in Yunnan are highly divergent from the progenitor of SARS-CoV-2. The first of these viruses reported by WIV, RaTG13, is certainly too divergent to be the progenitor of SARS-CoV-2, providing key genetic evidence that weakens the notion of a “laboratory leak.” Furthermore, three other sarbecoviruses collected in Yunnan independently of WIV are now the closest bat coronaviruses to SARS-CoV-2 that have been identified: RmYN02, RpYN06, and PrC31.
So how did SARS-CoV-2 jump to humans? While it's possible the virus spread through direct bat-human contact, a known risk for SARS-CoV, the first cases of SARS-CoV-2 detected in December 2019 are linked to wet markets in Wuhan. This is consistent with multiple spillover events associated with the animal market in November and December. It's currently not possible to be certain about the animal source of SARS-CoV-2, but it's noteworthy that live animals, including civet cats, foxes, mink, and raccoon dogs—all susceptible to sarbecoviruses—were for sale in Wuhan markets, including the Huanan market (identified as the epicenter of the outbreak in Wuhan), throughout 2019. Many of these animals are farmed on a large scale for their fur and then sold to animal markets. Some of these farmed species (American mink, red foxes, and raccoon dogs) were sold live as food by animal vendors in Wuhan, as was trapped wildlife (including raccoon dogs and badgers), although no bat species were for sale. Taken together, this suggests a central role for live intermediate hosts susceptible to SARS-CoV-2.