Slack / Private Message Drop — page 779

*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 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 (Annex E2, Table 1 of WHO, 2021). 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 (Molecular Epidemiology Table 7, sample 13 in WHO, 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, Molecular Epidemiology Table 7, sample 06 in WHO, 2021) 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 (Rambaut et al., 2020; Worobey et al., 2020). ``` ``` [2021-05-11 15:48:07] [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 animal 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. ``` Figure 1. Natural scenarios of SARS-CoV-2 origin. Natural spillover directly from a bat or via an intermediate host may have involved trade in wildlife susceptible to SARS-CoV-2, either trapping and hunting of wildlife in nature or farming of "wildlife species." There is now clear evidence that SARS-CoV-2 is capable of effective spread, not only in humans, but to a diverse group of mammals (Garry, 2020). The multi-market aspect of the early outbreak can be explained by distribution of SARS-CoV-2 infected animals to more than one market (Fig. 1). In Natural scenarios diversification of SARS-CoV-2 to lineages A and B could have occurred prior to the distribution, either at a wildlife farm or during transport of the animals to the markets. It is possible that humans involved in the wildlife trade were also infected and involved in this pathway. Figure 2. Lab Leak scenarios of SARS-CoV-2 origin. ``` 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 (Relman 2020; Butler et al., 2021). Pangolins carry and appear to be naturally infected with at least two lineages of sarbecoviruses (Liu et al., 2019; Lam et al., 2020). The Guangdong strain of pangolin coronavirus carries a receptor binding domain (RBD) that is highly similar to the RBD of SARS-CoV-2 (Lam et al., 2020, Andersen et al., 2020). 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