The first large cluster of infections was associated with the Huanan Seafood Market, and retrospective analyses of influenza-like-illness patients and blood donations in Wuhan found no evidence of earlier circulation.
Sampling of many individuals prior to December 2019 showed no positives for SARS-CoV-2 antibodies, suggesting that the virus did not spread widely before the market outbreak.
The Wuhan Institute of Virology is not known to have possessed a sufficiently close backbone strain to engineer SARS-CoV-2, and there is no public data indicating they had undisclosed viruses that match it.
Specific genomic features, like the furin cleavage site, appear suboptimal for an engineered virus (e.g. the PRRAR sequence and an out-of-frame insertion), which fits with a virus evolving naturally rather than through targeted gain-of-function work.
Several closely related bat coronaviruses have partial insertions near the S1/S2 region, suggesting that such changes can occur naturally over time and need not be artificially inserted.
A negative binomial pattern of SARS-CoV-2 transmission, with many zero-spreader events and a small number of superspreader events, is consistent with a spillover followed by rapid amplification in a crowded market setting.
Evidence of multiple potential intermediate animal hosts (e.g. wildlife farmed animals) further increases the probability that a bat coronavirus evolved into SARS-CoV-2 through natural spillover events rather than intentional engineering.
Early cases identified at the market and lack of widespread pre-epidemic infection clusters elsewhere in Wuhan align with the idea of a swift zoonotic jump to humans in late 2019.