Outside the Huanan Seafood Wholesale Market in Wuhan, China in March 2020 after its closure. Credit: Chinanews.com/China News Service via Wikimedia Commons.
In three new studies published over the weekend, scientists from a variety of organizations and countries have come to the same conclusion: SARS-CoV-2 originated at a seafood market in Wuhan, China, jumping from animals to humans and kicking off a 2+ year pandemic in November/December 2019.
Scientists and the general public have long suspected the Huanan Seafood Wholesale Market in Wuhan to be the epicenter of the pandemic; but, there were other more controversial theories as well, including the idea that SARS-CoV-2 was cooked up in a Chinese laboratory. These three studies, which are pre-prints and have not been per-reviewed yet, provide convincing evidence of the market as the birthplace through a variety of scientific methods.
For example, in Worobey, M. et al., the scientists use epidemiological, genomic, commercial, photographic, location, social mobility and survey data from a range of sources to explore the hypothesis that COVID-19 began at the Huanan market. Using spatial analysis to examine 156 COVID-19 cases in December 2019, the team showed that most of the early cases were highly focused at or near to the Huanan market. They also demonstrated that the clustering of early cases is best explained by proximity to the market—not population density or demographics.
Looking at the genomic data, two distinct lineages of SARS-CoV-2 circulated the globe in the early days of the pandemic. Genome sequences from lineage B—but not lineage A—had been reported from cases and/or environmental samples associated with the Huanan market. Performing genomic analysis with case location data, the scientists were surprised to see that lineage A was actually closer to the market than lineage B—1.17 km compared with 1.90 km for cases epidemiologically linked to the area and 9.11 km for those unlinked.
“These analyses—unlike what we had hypothesized—show that at an early time point in the epidemic both the ‘A’ and the ‘B’ lineages of SARS-CoV-2 were geographically associated with the Huanan market,” the scientists write in their paper. “These findings suggest that both lineages may have spilled over at the Huanan market during the beginning stages of the COVID-19 pandemic in Wuhan, with the limited geographic dispersal of lineage A compatible with a more recent zoonotic event.”
Lastly, of the cases epidemiologically linked to the market, the overwhelming majority were specifically linked to the western section of the Huanan market, where most of the vendors selling SARS-CoV-2-susceptible live mammals—including Asian raccoon dogs, hog badgers and red foxes—were located.
Gao, G. et al., also found a substantial link between the western portion of the market and the early cases of COVID-19. The Chinese-based research team analyzed 828 environmental samples collected from inside the market, with 64 (8%) testing positive for SARS-CoV-2. Of the 64, 56 (88%) were collected in the western zone of the market.
While Gao and co-authors did not detect live virus in any of the 457 animal samples collected across 18 species, the SARS-COV-2 nucleic acids in the positive environmental samples did show significant correlation of abundance of Homo sapiens with SARS-CoV-2.
“SARS-CoV-2 RNA was detected in stalls in the western zone of [Huanan Seafood Wholesale Market], suggesting the prevalence of SARS-CoV-2 in the market. Thus, the market might have acted as an amplifier due to the high number of visitors every day, causing many initially identified infection clusters in the early stage of the outbreak,” the scientists conclude in their study.
A third study by Pekar, J.E., et al. also examined the two distinct viral lineages—A and B—that characterized the early COVID-19 infections. By combining genomic data, epidemiological data, novel phylodynamic models and epidemic simulations, the team demonstrated that the two lineages were the result of at least two separate zoonotic events.
For example, the earliest lineage A genome belongs to an individual who lived just south of the Huanan market, while the second oldest belongs to a person who stayed at a hotel near the market. As also shown in Worobey et al., these two cases were more closely positioned to the Huanan market than lineage B samples from the Wuhan population and/or COVID-19 cases in the city in early 2020.
“This geographic proximity is consistent with lineage A emerging from the same location as lineage B, but starting at a later point in time,” the researchers explain. “[The results] suggest two separate zoonotic transmissions starting no earlier than November 2019, with a lineage A virus jumping into humans after the introduction of a lineage B virus.”
That being said, none of the studies were able to determine the animal associated with the zoonotic events. Worobey et al., seems to make a case for raccoon dogs since they have already been associated with the emergence of SARS-CoV-1, and have been shown to be both susceptible to infection with SARS-CoV-2 and capable of transmitting the virus.
Pekar, J.E. et al. even went so far as to reconstruct a hypothetical progenitor of SARS-CoV-2 across 15 non-recombinant regions from bat sarbecovirus genomes. The results led the researchers to conclude that even if SARS-CoV-2 originated with bats—who are carriers of the virus—the zoonotic jumps occurred from an “as-yet undetermined, intermediate host animal at the Huanan Seafood Wholesale Market.”