New clues to pandemic's origin surface, causing uproar.

Genetic sequences from Wuhan market may point to animal that spread SARS-CoV-2, but data remain hidden.

A Critical Analysis of the Evidence for the SARS-CoV-2 Origin Hypotheses.

When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.

Wildlife trade is likely the source of SARS-CoV-2.

Multiple transmissions from wildlife at a market in Wuhan probably led to SARS-CoV-2 emergence.

The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic.

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2-susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic.

Transmission history of SARS-CoV-2 in humans and white-tailed deer.

The emergence of a novel pathogen in a susceptible population can cause rapid spread of infection. High prevalence of SARS-CoV-2 infection in white-tailed deer (Odocoileus virginianus) has been reported in multiple locations, likely resulting from several human-to-deer spillover events followed by deer-to-deer transmission. Knowledge of the risk and direction of SARS-CoV-2 transmission between humans and potential reservoir hosts is essential for effective disease control and prioritisation of interventions. Using genomic data, we reconstruct the transmission history of SARS-CoV-2 in humans and deer, estimate the case finding rate and attempt to infer relative rates of transmission between species. We found no evidence of direct or indirect transmission from deer to human. However, with an estimated case finding rate of only 4.2%, spillback to humans cannot be ruled out. The extensive transmission of SARS-CoV-2 within deer populations and the large number of unsampled cases highlights the need for active surveillance at the human-animal interface.

Novel viruses highlight risks of Asia's wild animal trade.

Sampling of game in China reveals many viral threats.

COVID-19-lessons for zoonotic disease.

Disease emergence is driven by human-animal contact in a global viral ecosystem.

Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study.

BACKGROUND: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. METHODS: In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. FINDINGS: Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. INTERPRETATION: Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. FUNDING: US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.

Alphacoronaviruses Are Common in Bats in the Upper Midwestern United States.

Bats are a reservoir for coronaviruses (CoVs) that periodically spill over to humans, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. A collection of 174 bat samples originating from South Dakota, Minnesota, Iowa, and Nebraska submitted for rabies virus testing due to human exposure were analyzed using a pan-coronavirus PCR. A previously partially characterized CoV, Eptesicus bat CoV, was identified in 12 (6.9%) samples by nested RT-PCR. Six near-complete genomes were determined. Genetic analysis found a high similarity between all CoV-positive samples, Rocky Mountain bat CoV 65 and alphacoronavirus HCQD-2020 recently identified in South Korea. Phylogenetic analysis of genome sequences showed EbCoV is closely related to bat CoV HKU2 and swine acute diarrhea syndrome CoV; however, topological incongruences were noted for the spike gene that was more closely related to porcine epidemic diarrhea virus. Similar to some alphaCoVs, a novel gene, ORF7, was discovered downstream of the nucleocapsid, whose protein lacked similarity to known proteins. The widespread circulation of EbCoV with similarities to bat viruses that have spilled over to swine warrants further surveillance.