Slack / Private Message Drop — page 775

release [Relman, 2020; Parisite 1, 2]. Some Lab Leak proponents have suggested that SARS-Cov-2 may be the product of laboratory passage of a progenitor virus in cell culture or animals, or Gain-of-Function research [ref]. New data presented by the WHO study provides clear findings in support of the Natural origin of SARS-CoV-2. Results The study of SARS-CoV-2 origins conducted by the WHO team provided important new data regarding the role of wildlife markets in the emergence of SARS-CoV-2. The large Huanan seafood market, which also sold wildlife and wildlife products, was a focus of early attention because it was linked to the majority of early cases of COVID-19 in Wuhan. The WHO report documented that early cases were not only linked to the Huanan market, but that other early cases were linked to different markets that sold wildlife or wildlife products. Among the first 168 diagnosed cases of COVID-19 in Wuhan with onset date prior to December 31, 2019 and a known history of exposure to wildlife markets 55.4% (93/168) reported such exposures. Of the 168 cases, 28% (47/168) had only been to the Huanan market, 22% (38/168) had exposure to another wildlife market and 4.7% (8/168) had exposure to the Huanan market and another market (ref table). The genetic lineages of SARS-CoV-2 associated with early cases in Wuhan were documented in the WHO report. Previously, Rambaut et al, (2020) noted that at the root of the phylogeny of SARS-CoV-2 are two lineages designated lineage A and B. Early lineage A viruses, include SARS-Cov-2 isolate EPI_ISL_529213 sampled on 30Dec19 from a person linked to a wildlife market different than the Huanan market (Table 7, S13, WHO report 2021). Linage A viruses share two nucleotides (T8,782 in ORF1ab and C28,144 in ORF8) with the bat viruses RaTG13 and RmYN02 and other sarbecoviruses. It is likely that the most recent common ancestor (MRCA) of SARS-CoV-2 shares the same genome sequence as these early lineage A sequences (Rambaut et al., 2020). Different nucleotides (C8,782 in ORF1ab and T28,144 in ORF8) are present at those sites in viruses assigned to lineage B, such as SARS-CoV-2 isolate Wuhan-Hu-1 (GenBank accession no. MN908947, Table 7, S13, WHO report,) sampled from the Huanan market on 30Dec19. All virus positive samples from the Huanan market, from venders or customers of the market or from environmental samples, contained SARS-CoV-2 of lineage B. There was limited genetic diversity in the lineage B samples from the Huanan market, which is consistent with the market as a site of a super-spreader event. Lineage A and Lineage B viruses spread throughout Wuhan and to other countries [ref]. [shared file(s): image.png, image.png] [2021-05-11 08:45:54] [Robert Garry] Competing hypotheses have been put forward to explain the emergence of SARS-CoV-2. Natural spillover directly from a bat or via an intermediate host could have occurred via several different scenarios (Fig. 1). Likewise, several variations of the Lab Leak hypothesis have been proposed (Fig. 2). A dispassionate science-based discourse on the topic of the origin of SARS-CoV-2 must account for this new data revealed by the WHO study showing: 1. multiple markets were linked to the early cases, and 2. divergence of SARS-CoV-2into lineages A and B was an early occurrence. These facts are represented by yellow boxes in each figure. Proponents of Lab Leak theories speculate that SARS-CoV-2 or a close progenitor was present in the Wuhan Institute of Virology or another Wuhan virology lab before the start of the COVID-19 pandemic and the appearance of the first cases in Wuhan (Fig. 2). It has been proposed that SARS-CoV-2 was released either via an infected laboratory worker, an escaped lab animal or via waste disposal (Parisite 1, Relman 2020). Pangolins carry and appear to be naturally infected with at least two lineages of sarbecoviruses [ref]. The Guangdong strain of pangolin coronavirus carries a receptor binding domain that is highly similar to the RBD of SARS-CoV-2. Some proponents of the Lab Leak theory have speculated the RBD of GD pangolin was recombined via genetic engineering with the backbone of an undisclosed sarbecovirus to produce SARS-CoV-2. Alternatively, it has been suggested that an undisclosed close progenitor of SARS-CoV-2 was passaged on human cells or experimental animals (such a humanized mice) in gain of function type experiments to adapt for human replication (Segreto and Deigin, 2020). The direct role of the Chinese military in conducting classified research on sarbecoviruses at the WIV has also been proposed (DoS). In Lab Leak scenarios diversification of SARS-CoV-2 to its two separate early lineages A and B would have had to occur in the laboratory setting. Lab Leak scenarios must also account for the fact that the majority of early cases were associated with different wildlife markets in Wuhan. [shared file(s): image.png, image.png] [2021-05-11 08:45:54] [Robert Garry] Discussion Lab Leak scenarios are inconsistent with several established facts regarding the origin of SARS-CoV-2. The majority of 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 on SARS-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 waste