Discussion Lab Leak scenarios are inconsistent with several established facts regarding the origin of SARS-CoV-2. The majorityof early cases were linked to different markets that sold wildlife or wildlife products in Wuhan. All theories of the origin of SARS-CoV-2 must account for the linkage to different market engaged in wildlife trade. Theories onSARS-CoV-2 must also account for the fact that two distinct lineages of SARS-CoV-2 were distributed at different Wuhan wildlife markets. Scenarios where an infected laboratory worker, an escaped lab animal or faulty wastedisposal spread not one but two lineages of SARS-CoV-2 specifically to different wildlife markets are difficult torationalize.The original SARS outbreaks in 2003 and 2004 were linked to the wildlife trade [ref]. In contrast to Lab Leak theories, linkage of the origin of SARS-CoV-2 to wildlife or the wildlife trade provides several plausible scenarios for the appearance of SARS-CoV-2 at different wildlife markets. It fully accounts for the fact that the majority of early Wuhan COVID-19 cases were linked to different wildlife markets in a straightforward manner. It also provides asimple explanation for the fact that two different lineages of SARS-CoV-2 were linked to markets. Divergence ofSARS-CoV-2 to lineages A and B is likely to had occurred prior to the transport of infected animals to Wuhan. Subsequently, t he infected animals were distributed to different wildlife markets. Proponents of the Lab Leak theory will point out that none of the animals sold at the Huanan Market tested positive for SARS-CoV-2 (WHO Report, 2021). Although mentioned in the WHO Report, but not discussed in detail, several independent sources indicate that wildlife species susceptible to SARS-CoV-2, including civets and raccoon dogs, were sold at the Huanan market (Holmes, CNN, other). Similar species were likely to have been available topurchase at other wildlife markets in Wuhan. Certain species of animals may have been removed after the appearance of the first COVID-19 cases and the linkage of COVID-19 cases to the market, but prior to the closure ofthe Market on January 1, 2020. It should also be noted that environmental samples that did test positive were associated with the portion of the market where wildlife or wildlife products were sold. A temporal analysis of the early human cases at the Huanan market confirms the pattern of spread from the areas of the market where wildlife products were sold to other parts of the market. (WHO report, 2021).A hybrid variation of the Natural and Lab Leak scenarios suggests that SARS-CoV-2 is a natural virus that infected ascientist while doing field work or after being brought back to a laboratory where it was stored or propagated and then released accidentally (Relman, 2020; Baker, 2020). Compared to the millions of worldwide encounters ofhumans with wildlife (in the wild or on wildlife farms), including the trapping of bats for food, the exposures of limited numbers of scientists doing field work is miniscule compared to the numbers of humans exposed in nature or during wildlife trade. Thus, this hybrid scenario is of very low probability. It also fails to explain how two lineages ofSARS-CoV-2 came to be distributed at the different wildlife markets. Conclusions New data compiled by the WHO team regarding the presence of distinct lineages of SARS-CoV-2 in different Wuhan wildlife markets are inconsistent with a laboratory-based origin of SARS-CoV-2.AcknowledgmentsKristian G. Andersen, Edward C. Holmes and Andrew Rambaut provided essential input and discussion. Work onemerging viruses in the Garry Laboratory is supported by the National Institutes of Health, the Coalition for EpidemicPreparedness Innovations, the Burroughs Wellcome Fund, the Wellcome Trust, the Center for Disease Prevention and Control, and the European & Developing Countries Clinical Trials Partnership.References [shared file(s): image.png, image.png]