Covid-19

Statisticians challenge claims that Covid-19 began in the Huanan seafood market

A recently published paper, and its analysis by two German researchers, constitute a fresh challenge to claims that Covid-19 began in the Huanan seafood market in Wuhan.

In their paper published in the Journal of the Royal Statistical Society, Dietrich Stoyan from the Institute of Stochastics in Freiberg, Germany, and Sung Nok Chiu from the Department of Mathematics at the Hong Kong Baptist University say statistics do not prove that the Huanan seafood wholesale market was the early epicentre of the Covid-19 pandemic.

The two researchers counter claims made by Michael Worobey, who heads the department of ecology and evolutionary biology at the University of Arizona in the US and is a leading proponent of the zoonosis hypothesis (the theory that SARS-CoV-2 made a zoonotic jump from an animal to humans). The other main hypothesis about SARS-CoV-2 is that it originated in a lab as a result of gain-of-function research.

Stoyan and Chiu said their paper, which was originally published as a preprint on arXiv in August 2022, aimed to critique the statistical methods employed by Worobey et al., not the source and quality of the data.

Worobey hit the headlines in February 2022 when two papers he co-authored were published as preprints (‘The Huanan market was the epicenter of SARS-CoV-2 emergence’ and ‘SARS-CoV-2 emergence very likely resulted from at least two zoonotic events’, both published on February 26).

The New York Time hailed the two studies as a “significant salvo” in the debate about the origins of the Covid-19 pandemic.

Worobey was quoted by the New York Times as saying: “When you look at all of the evidence together, it’s an extraordinarily clear picture that the pandemic started at the Huanan market.”

The papers co-authored by Worobey did not, however, identify an animal at the Huanan seafood market that spread SARS-CoV-2 to humans.

The preprints later passed peer review and a new paper, ‘The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the Covid-19 pandemic’ was published in Science on July 26, 2022.

In this paper Worobey et al. refer to 155 cases of Covid-19 for which they said they were able to “reliably extract” the latitude and longitude coordinates from the report of the ‘Joint WHO-China Study’ of the possible origins of SARS-CoV-2  that took place from January 14 to February 10, 2021.

The WHO-China report was published on March 30, 2021, and stated that, at that time, “no firm conclusion” about the role of the Huanan market in the origin of the outbreak could be drawn.

Stoyan and Chiu said they had come to a clear conclusion: that the analysis in the paper by Worobey et al. that was published in Science did not give “an acceptable argument for the centrality of the market in the 155 December cases”.

The two researchers wrote: “We show that this statistical conclusion is invalid on two grounds: (a) The assumption that a centroid of early case locations or another simply constructed point is the origin of an epidemic is unproved. (b) A Monte Carlo test used to conclude that no other location than the seafood market can be the origin is flawed. Hence, the question of the origin of the pandemic has not been answered by their statistical analysis.”

Stoyan and Chiu said their own analysis suggested that the market as well as some other points in its neighbourhood or some other landmarks like the Wanda Plaza were possible spatial ‘centres’ of the cases.

“Neither W’s [Worobey’s] nor our statistical analysis could be used to support or reject the zoonosis hypothesis,” they wrote.

Stoyan and Chiu noted that the paper by Worobey et al. that was published in July 2022 attracted worldwide attention and media coverage and was downloaded almost 400,000 times in the ten months after it was published.

At the request of the German newspaper Frankfurter Allgemeine Zeitung (FAZ) two independent experts in spatial statistics – René Westerholt from Dortmund Technical University and Evgney Spodarev from Ulm University – analysed Stoyan and Chiu’s findings.

FAZ said Westerholt came to a similar assessment to that reached by Stoyan and Chiu: that the methodology of the study reported on in the article in Science in July 2022 was inadequate.

Westerholt said the analysis of 155 cases of Covid referred to in the paper by Worobey et al. could not rule out that places near the wet market were a possible origin of Covid-19, but he did not accept some of the conclusions drawn by Worobey at al., FAZ reported.

Although they provided strong evidence of early infection events in the vicinity of the market, the conclusions drawn “could not be made in full and to the extent communicated”, Westerholt was quoted as saying.

Spodarev also said Stoyan and Chiu’s conclusions were correct, FAZ reported. The newspaper quoted Spodarev as saying the spatial statistical analysis in Worobey et al.’s study was “flawed in multiple ways”.

FAZ also quoted Spodarev as saying that Worobey et al. assumed that the source of the Covid-19 pandemic was local and immobile. According to Spodarev, there was “careless and unprofessional handling of statistical methodology” by Worobey et al.

Hinnerk Feldwisch-Drentrup, reporting for FAZ, quoted Stoyan as saying the statistical test chosen by Worobey et al. was “blatantly nonsensical”.

Always calculating the distance to the market with randomly generated point clouds (datasets that represent objects or space) automatically created large distances, which was to be expected and not surprising, Stoyan was quoted as saying.

There was also a lack of a realistic model for disease clusters, Stoyan was quoted as saying. Stoyan said he was “deeply disappointed” that Science magazine published the paper by Worobey et al., Feldwisch-Drentrup reported.

Worobey is reported to be working with a colleague on a scientific response to the paper written by Stoyan and Chiu.

The South China Morning Post quoted him as saying that the paper by Stoyan and Chiu was “riddled with errors, both factual and statistical”.

The DRASTIC group of independent investigators and scientists had already challenged Worobey’s claims in a report they published in October 2022.

“We find that the arguments by Worobey et al. that SARS-CoV-2 emerged from the Huanan seafood market via zoonosis and the hypothesis that at least two separate zoonotic jumps from wild animals occurred at the HSM are not supported by data,” the independent investigators state in their report.

Zhang et al. state: “We find that the datasets and analyses put forward in support of zoonosis are biased, and lack sufficient verifiable data to support this hypothesis.”

They point to three studies: one by researchers at the Wuhan Institute of Virology and Huazhong Agricultural University (HZAU), one by Wu et al., and a more extensive study by Gao et al. All the studies concluded that the Huanan seafood market was likely to be a superspreader location and not the source of SARS-CoV-2.

“Consequently, we conclude the most likely scenario is that an infected person brought the virus to the HSM, sparking a superspreader event.”

The report published on zenodo.org on October 9 was written by four independent investigators (Daoyu Zhang, Gilles Demaneuf, Adrian Jones, and Yuri Deigin¹), along with the founder of Seattle-based Atossa Therapeutics Steven Quay, Steven Massey from the University of Puerto Rico, and Louis Nemzer from the Halmos College of Arts and Sciences at Nova Southeastern University in Florida in the US.

“We concur with this conclusion, as the earliest case locations are removed from wildlife stalls, no wildlife seller contracted Covid-19, SARS-CoV-2 positive environmental specimens are most strongly associated with human gene sequences, and no animals tested positive for the virus,” Zhang et al. state.

“Furthermore the distribution of Covid-19 cases are not consistent with a single point source and instead exhibit a distribution consistent with a Poisson point process model², and are consistent with human-to-human transmission in shared communal areas such as eating areas and toilets.”

The researchers add that four of the earliest identifiable cases of Covid-19 with onset from December 10 to 16, 2019, were not linked to the Huanan seafood market, “clearly indicating human-to-human transmission outside of the HSM …”.

They say the distribution of environmental PCR-positive samples is more spatially consistent with Covid-19 case contamination and spread from the HSM toilets than from wildlife stall locations.

“Furthermore, the very small quantities of potentially susceptible wild animals sold in Wuhan markets relative to other cities and towns in China where wild game is widely eaten makes an outbreak in Wuhan – and only Wuhan of all places in China – extremely unlikely from a probability perspective,” Zhang et al. add.

Alina Chan, who is co-author of the book  ‘VIRAL: The Search for the Origin of Covid-19′, said in an article published on Medium in July 2022 that, after peer review, “unscientific language” was removed from the Worobey et al. manuscript.

“However, these strong claims in the preprint had already been widely reported in the media back in February 2022,” Chan said.

Chan tweeted: “In order to argue for a market origin, Worobey and Pekar et al. had to (i) rule out the more likely scenario of a later infected case bringing the B variant to the market and (ii) explain why none of the early market cases had been infected with the A variant.

“This is why they came up with the 2 strains 2 spillover hypothesis, which stands on incredible shaky legs.”

Chan says in her Medium article that all of the observations that Worobey et al. cite as signs that the market was the outbreak epicenter “can be easily explained by the ascertainment bias with which early cases were identified”.

Chan noted that there were no longer claims of “dispositive or incontrovertible evidence” in the peer-reviewed paper, and the peer-reviewed paper had an entirely new section about study limitations, in which the authors acknowledged that they did not have access to the early Covid-19 case data or locations, lacked direct evidence of a market animal infected with the pandemic virus, and lacked complete details of how the market had been sampled for the virus.

She added: “At the very least, after peer review, the Worobey et al. 2022 paper now says: ‘However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there.’”

Ben Cowling, who is an epidemiologist and medical statistician at the School of Public Health at the University of Hong Kong told the South China Morning Post that he found Stoyan and Chiu’s argument compelling.

Cowling was quoted as saying that any analysis of the early cases, which were all severe, might not capture the full picture of the early epidemic.

“Only about five per cent of Covid-19 cases were severe at that time, so for every case that was identified probably there were at least another 19 cases that were not identified. In addition, not every severe case was identified,” he was quoted as saying.

Senior fellow at The Atlantic Council Jamie Metzl, who was formerly a member of the World Health Organisation’s expert advisory committee on human genome editing, tweeted the following:

The report of the 2021 ‘Joint WHO-China Study’ states: “Many of the early cases were associated with the Huanan market, but a similar number of cases [of Covid-19] were associated with other markets and some were not associated with any markets.

“Transmission within the wider community in December could account for cases not associated with the Huanan market which, together with the presence of early cases not associated with that market, could suggest that the Huanan market was not the original source of the outbreak.

“Other milder cases that were not identified, however, could provide the link between the Huanan market and early cases without an apparent link to the market.

“No firm conclusion therefore about the role of the Huanan market in the origin of the outbreak, or how the infection was introduced into the market, can currently be drawn.”

  1. Zhang, Demaneuf, and Massey are members of the original DRASTIC group (the Decentralised Radical Autonomous Search Team Investigating Covid-19). Deigin formed a new group entitled Designated Research and Scientific Team Investigating Covid-19, and Jones and Zhang are both members.
  2. A Poisson process is a stochastic process (a mathematical description of random events that occur one after another). It counts the number of occurrences of an event leading up to a specified time.

 

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