August 18, 2022

More evidence that covid-19 started in a market, not a laboratory

More evidence that covid-19 started in a market, not a laboratory
More evidence that covid-19 started in a market, not a laboratoryMore evidence that covid-19 started in a market, not a laboratory

TWO NEW papers provide more robust answers than heretofore available to three of the outstanding questions of the covid-19 pandemic: how, when and where SARS-CoV-2, the virus that caused it, first appeared in human beings. These papers, so-called preprints (meaning they have not yet gone through the formal process of peer review that precedes publication in a journal) were written by related teams of researchers from institutions around the world and posted to Zenodo, a repository for such documents. They conclude that, by November 2019, the virus was present in animals on sale at the Huanan Seafood Wholesale Market in Wuhan (pictured), whence it jumped to human hosts on two separate occasions a week or so apart.

One paper, the lead authors of which are Michael Worobey at the University of Arizona and Kristian Andersen of Scripps Research, in San Diego, attempts to trace the first infections definitively to the Huanan market. The authors used three approaches. First, by looking at the geographic distribution of early infections, they found that the market is in the region where the first covid-19 cases were most densely packed—a result that remains unchanged even when cases with no known link to the market are plotted. Second, they employed photographic evidence posted on Weibo, a Chinese social-media website, as well as contemporary accounts, to show that the market, which vends other goods besides seafood, was selling animals susceptible to the virus (a list that includes porcupines, marmots and raccoon dogs) prior to December 2019.

Third, they analysed the distribution of almost 600 environmental samples taken from the market by the Chinese Centre for Disease Control and Prevention (CCDC) in January 2020, after it had been shut down by the authorities. Combining this analysis with a recreation of the market layout, the authors showed that samples containing the virus were associated with stalls selling live animals, particularly in the market’s south-western corner.

The second paper, the lead author of which was Jonathan Pekar of the University of California, San Diego, examines the evolution of the virus in its earliest days in humans. At this time two forms, known as lineages A and B, predominated. These differ in the nature of two particular nucleotide loci (links in the RNA chain that constitutes the virus’s genome), with lineage A having a structure identical to similar viruses found in bats.

This suggests that lineage A was the original form and lineage B a subsequent mutation. However, the first known human cases involved lineage B. To resolve this conundrum, the researchers analysed nearly 800 almost-complete viral genomes from samples taken before February 14th 2020, to identify the most likely evolutionary paths taken by the virus.

This analysis showed that, while both lineages were present in cases in the vicinity of the market, no samples contained either any transitional form or any shared common ancestor. It therefore seems likely that the lineages made independent leaps into human hosts: lineage B on or around November 25th 2019, and lineage A a week or so later. Such multiple jumps from animals are common in coronaviruses. The viruses responsible for both the SARS outbreak in 2002 and MERS (Middle East respiratory syndrome), which appeared in 2012, are also thought to have started with multiple spillover events.

Doubling down on an explanation
All that the researchers felt they needed to make their case watertight was evidence of lineage A at the market. When they started work, all samples from there had contained only lineage B. This changed shortly before their papers went online, because of a detail buried in an unrelated preprint from a team at the CCDC. In a reanalysis of samples, this group discovered the first market-linked evidence of lineage A—on a discarded glove. “This really seals the deal,” says Dr Worobey. “Beyond all reasonable doubt we now know what happened.”

Though the papers are preprints, their analysis has been praised by numerous independent researchers. Assuming they are indeed correct, rival hypotheses have a steep hill to climb. The most popular of these, as well as the most contentious, is that the virus escaped from a laboratory in Wuhan before triggering a “superspreader” event at the market. The existence of two separate lineages at Huanan, says Dr Worobey, as well as the market’s central location in the density map of cases, suggests that such a lab leak would have had to have happened twice, while leaving no evidence yet discovered of the laboratory’s involvement on either occasion. That seems unlikely. Which animal species were responsible, though, remains to be determined.

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