Since the first reports of a novel SARS-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how SARS-CoV-2 emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.

Evidence supporting a zoonotic origin of SARS-CoV-2 Coronaviruses have long been known to present a high pandemic risk. SARS-CoV-2 is the ninth documented coronavirus that infects humans and the seventh identified in the last 20 years (Lednicky et al., 2021; Vlasova et al., 2021). All previous human coronaviruses have zoonotic origins, as have the vast majority of human viruses. The emergence of SARS-CoV-2 bears several signatures of these prior zoonotic events. It displays clear similarities to SARS-CoV that spilled over into humans in Foshan, Guangdong province, China in November 2002, and again in Guangzhou, Guangdong province in 2003 (Xu et al., 2004). Both these SARS-CoV emergence events were associated with markets selling live animals and involved species, particularly civets and raccoon dogs (Guan et al., 2003), that were also sold live in Wuhan markets in 2019 (Xiao et al., 2021) and are known to be susceptible to SARS-CoV-2 infection (Freuling et al., 2020).

Animal traders working in 2003, without a SARS diagnosis, were documented to have high levels of IgG to SARS-CoV (13% overall and >50% for traders specializing in civets; Centers for Disease Control and Prevention, 2003). Subsequent serological surveys found ~3% positivity rates to SARS-related coronaviruses (SARSr-CoV) in residents of Yunnan province living close to bat caves (Wang et al., 2018), demonstrating regular exposure in rural locations. The closest known relatives to both SARS-CoV and SARS-CoV-2 are viruses from bats in Yunnan, although animals from this province have been preferentially sampled. For both SARS-CoV and SARSCoV2 there is a considerable geographic gap between Yunnan and the location of the first human cases, highlighting the difficulty in identifying the exact pathway of virus emergence and the importance of sampling beyond Yunnan.