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The Origins of SARS-CoV-2

Our take —

In this preprint that has not yet been peer-reviewed, the authors assess the current evidence on the origins of the SARS-CoV-2 virus. Data available are more consistent with spillover of the virus from an animal source, possibly from one or more live animal markets in Wuhan, than a leak or intentional release from the Wuhan Institute of Virology. However, we have very limited information on the sequence of events that led to the emergence of the virus, and conclusive evidence on emergence of SARS-CoV-2 remains elusive.

Study design

Other

Study population and setting

The paper summarizes findings from the published literature and from the World Health Organization report on investigations into the origins of SARS-CoV-2. The authors weigh the current evidence in support of a natural origin of the virus versus other explanations, notably an accidental or intentional leak of the virus from the Wuhan Institute of Virology.

Summary of Main Findings

No direct evidence of a spillover event of SARS-CoV-2 from an animal host to humans has been identified. However, the authors summarize several lines of evidence that support a zoonotic origin of SARS-CoV-2: 1) human-animal contacts at live animal markets in Wuhan in 2019 were similar to those identified as part of the emergence of SARS-CoV in 2002-2003; 2) the epidemiology in the early phase of the epidemic in Wuhan, suggesting links to a live animal market; and 3) the identification of the closest relative to SARS-CoV-2 in wildlife rather than in sequences catalogued by the Wuhan Institute of Virology.

Fifty-five percent of the earliest human cases identified in Wuhan during December 2019 had a link to a live animal market and the home addresses of cases through December 2019 were clustered north of the Yangtze River nearby to the Huanan Seafood Market and other live animal markets. Live animals with known susceptibility to SARS-CoV and SARS-CoV-2 (e.g., civets, raccoon dogs) were reportedly being sold in markets in Wuhan as late as December 2019. The districts reporting excess deaths in mid-January 2020 were also those containing live animal markets.

This epicenter of the outbreak was >10km from the Wuhan Institute of Virology, and only a few cases were reported from this district in December; no cases reported had a connection to the laboratory and excess deaths were not detected in this district until late January or early February 2020. The laboratory reported in July 2020 (https://www.doi.org/10.1126/science.abd9835 [https://www.doi.org/10.1126/science.abd9835]) that no current members of the laboratory staff had evidence of antibodies against SARS-CoV-2. However, information on when samples were collected from staff, how many individuals were tested, and whether any members had left the laboratory between the beginning of the pandemic and when samples were collected was not provided.

Viruses related to SARS-CoV-2 have been identified in bats and pangolins, but the closest related viruses to date are from bats in China and Thailand. The bat virus RaTG13, described from samples collected and sequenced by the Wuhan Institute of Virology, is not the closest relative of SARS-CoV-2; viruses from bats in Yunnan and Thailand are actually more closely related to SARS-CoV-2 than RaTG13, and these viruses were not identified by Wuhan researchers.

Initially, the furin cleavage site in the spike protein of SARS-CoV-2 was described as unusual, raising concern about virus origins. However, further investigation shows that this feature is present in several other animal coronaviruses, including other betacoronaviruses, further supporting a natural origin.

Study Strengths

While the article provides no new data, it is a synthesis of the available evidence on the epidemiology of the early outbreak, viral genetics, and evolution alongside evidence presented to the WHO team investigating the emergence in China.

Limitations

The biggest limitation is that comprehensive investigation of either the zoonotic or laboratory origin hypotheses have not been conducted. Plans for these investigations remain unclear and, due to the substantial amount of time that has elapsed since the emergence event, conclusive evidence may be unattainable.

Value added

This review may be seen as an update to the Andersen et al. article from 2020 on the proximal origins of SARS-CoV-2 (https://doi.org/10.1038/s41591-020-0820-9 [https://doi.org/10.1038/s41591-020-0820-9]). Additional epidemiologic evidence from the WHO report is consistent with a natural, zoonotic origin, although substantive knowledge gaps about origins remain.

This review was posted on: 1 September 2021