• Dissecting the early #COVID-19 cases in Wuhan

    Therefore, the preponderance of early cases connected to Huanan Market could not have been an artifact of ascertainment bias introduced by case definitions in the VPUE system. Although mechanisms like China’s VPUE system are potentially invaluable, they will fail without both widespread buy-in from health care providers and rapid data sharing from local to central authorities. Key problems with the VPUE system were known before the pandemic, including that most clinicians in China had little awareness of the VPUE system and were not reporting cases to it—for example, 0 of 335 PUE cases in one study from 2019 (5). China should be commended, however, for having such a system, which is lacking in most countries. The focus now should be on fixing the problems that COVID-19 has exposed and blanketing the globe with a highly functional PUE early warning system.

    Samples from the earliest COVID-19 patients in Wuhan have been sequenced, and two distinct SARS-CoV-2 lineages, A and B, have been identified. Given that the elderly couple at HPHICWM was the WHO report’s cluster 1, it follows that the husband, illness onset 26 December (1), must be the source of the earliest lineage A sequence, Wuhan/IME-WH01/2019 (GenBank accession number MT291826) (see fig. S1), which he most likely got from his wife, who became ill 15 December. This raises the possibility that the Yangchahu market that they visited may have been a site of a separate animal spillover. The recent discovery that there may be no true lineage A or B intermediates in humans (15) also raises the possibility of separate spillovers of both lineages. However, the earliest known lineage A genomes have close geographical connections to Huanan Market: one from a patient (age and gender not reported) who stayed in a hotel near Huanan Market in the days before illness onset in December (13) and the other from the 62-year-old husband in cluster 1 who visited Yangchahu Market, just a few blocks north of Huanan Market (1), and lived just to the south (see the figure). Therefore, if lineage A had a separate animal origin from lineage B, both most likely occurred at Huanan Market, and the association with Yangchahu Market, which does not appear to have sold live mammals, is likely due to community transmission starting in the neighborhoods surrounding Huanan Market.

    With SARS, live-animal markets continued to sell infected animals for many months, allowing zoonotic spillover to be established as the origin and revealing multiple independent jumps from animals into humans (3). Unfortunately, no live mammal collected at Huanan Market or any other live-animal market in Wuhan has been screened for SARS-CoV-2–related viruses (1), and Huanan Market was closed and disinfected on 1 January 2020. Nevertheless, that most early symptomatic cases were linked to Huanan Market—specifically to the western section (1) where raccoon dogs were caged (2)—provides strong evidence of a live-animal market origin of the pandemic.
    This would explain the extraordinary preponderance of early COVID-19 cases at one of the handful of sites in Wuhan—population 11 million—that sell some of the same animals that brought us SARS. Although it may never be possible to recover related viruses from animals if they were not sampled at the time of emergence, conclusive evidence of a Huanan Market origin from infected wildlife may nonetheless be obtainable through analysis of spatial patterns of early cases and from additional genomic data, including SARS-CoV-2–positive samples from Huanan Market, as well as through integration of additional epidemiologic data. Preventing future pandemics depends on this effort.