Air Force Senior Airman Jada Williams and Air Force Airman 1st Class Daniella De Mier Eusse, medical technicians assigned to the Air Force military medical team deployed to Lawrence, Mass., take part in postmortem care training from Judy Michaud, a professional development specialist for Lawrence General Hospital, as part of COVID-19 response operations in Lawrence, Mass., Feb. 11, 2022. Photo By: Army Spc. Daniel Thompson.
SARS in 2003 and MERS in 2012 resulted from natural spillover events in which animals infected humans with coronaviruses. In both cases, two convincing lines of evidence were obtained: (1) the viruses-and/or antibodies to the viruses were identified both in humans and in animals, and (2) humans with occupational exposures to animals exhibited higher rates of seropositivity to the viruses than the general human population. So far, studies attesting to natural spillover of COVID-19—including some recently highlighted in the press—fail to meet these criteria.
SARS. In the case of SARS (severe acute respiratory syndrome), the evidence was clear that the virus came from animals. One study sampled animals being sold at a live animal market in Guangdong, China and found viruses in palm civets that had genome sequences 99.8 percent identical to the human SARS virus. These viruses were closely related to SARS-CoV. Another study found that 80 percent of the palm civets from the animal market in Guangzhou tested positive for SARS-CoV antibodies. The earliest SARS patients butchered or cooked wild animals and thus had occupational exposures to SARS-CoV.
An epidemiologic study in the Guangdong Province tested almost 800 people for Immunoglobulin G (IgG) antibodies to SARS-CoV. Individuals who traded primarily masked palm civets had the highest positivity rates, almost 73 percent. The Chinese SARS Molecular Epidemiology Consortium used whole-genome sequencing to track early cases and the molecular evolution of the SARS virus. They determined that two major viral genotypes predominated during the initial phase of the epidemic. One genotype was virtually identical to samples collected for sale and from humans working in a live animal market in Shenzhen. The other genotype was identical to samples collected from farmed civets and in the earliest human cases in Zhongshan. The conclusion: compelling evidence for an animal origin of SARS-CoV.
MERS. After the emergence of MERS (Middle East respiratory syndrome) in humans, researchers found that dromedary camels throughout the Middle East, North and East Africa, and parts of Asia tested positive for MERS-CoV antibodies. Archived dromedary camel blood specimens dating back decades tested positive for MERS-CoV antibodies, indicating that cross-reacting viruses had been circulating in camels for decades.
A serological survey of over 10,000 healthy human adults from all 13 provinces of Saudi Arabia from 2012 to 2013 found MERS-CoV antibodies in 0.15 percent of samples. For camel shepherds, MERS-CoV antibody seropositivity rates were 15 times higher and for slaughterhouse workers, they were 23 times higher than the general population, respectively. The conclusion: compelling evidence for an animal origin of MERS-CoV.
COVID-19. In contrast to SARS and MERS, there is no direct evidence for a natural spillover of COVID-19. Neither the virus nor antibodies to the virus have been identified in animals sampled in Wuhan in 2019 or early 2020. In an article currently undergoing peer review, Gao et al. found that zero out of 457 samples taken from 18 species of animals sampled in Wuhan in early 2020 tested positive for SARS-CoV-2. In addition, no correlation has been observed between human occupational exposures to animals and higher rates of infection or seropositivity to the virus.
By early 2020, Chinese physicians had conducted many serological surveys of thousands of people to assess prevalence rates of SARS-CoV-2 antibodies, but none included data on occupation. Had occupations been included, these might have revealed whether animal workers in the Huanan market had higher rates of SARS-CoV-2 antibodies than in the general population, thereby supporting the natural spillover hypothesis.
Two recent papers, Worobey et al. and Pekar et al., present geospacial analysis of animal stalls in the Huanan market and viral phylogenetic analysis but do not provide convincing evidence of natural spillover. The data and analyses discussed by Worobey are equally consistent with both hypotheses: (1) that SARS-CoV-2 first entered humans at the Huanan Seafood Market in Wuhan, and (2) that SARS-CoV-2 first entered humans at another location and was subsequently brought to the market and then amplified in the market by humans. The authors’ assertion that the data and analyses support only the natural spillover hypothesis is false.
Gao et al. reached a conclusion opposite to the claims of Worobey et al. and Peckar et al. Gao et al. reported that there were no positive animal samples at the Huanan market. They further reported that there was no correlation between the locations of the animal sellers in the market or the locations with the highest densities of humans and the locations of the positive environmental samples in the market. Based on these findings, Gao et al suggested that the market “acted as an amplifier,” with infections being brought into the market by humans infected elsewhere.
The hypothesis that SARS-CoV-2 originated from a laboratory-related spillover—for example, from a laboratory-acquired infection—remains a viable possibility. Laboratory accidents, including laboratory-acquired infections, occur frequently. In the most recent year for which data are available, the CDC/USDA Select Agent Program received 205 select agent theft/loss/release reports, which equates to an average of four select-agent incidents per week. Of the 205 select-agent theft/loss/release reports, fully 196 were reports of releases and 177 were “determined to represent potential occupational exposure to laboratory workers.”
In determining the origin of SARS-CoV-2, what is needed, at a minimum, is: (1) data from serological sampling in 2019 and early 2020 that includes information on occupation and location and that encompasses both Wuhan animal market employees and Wuhan laboratory research employees, and (2) information—including samples, sequences, records, and results—on the research on SARS-related coronaviruses conducted by Wuhan researchers and their collaborators in 2015-2019.
Science is the objective pursuit of truth. Preventing future COVID-19 pandemics requires finding the truth. Premature, false declarations of “dispositive evidence” or “proof” does not generate public trust in science and does not protect public health.
Acknowledgments: Kahn would like to thank Elisa Harris, Milton Leitenberg, and Richard Ebright for their invaluable comments, edits, and suggestions.
The Bulletin elevates expert voices above the noise. But as an independent, nonprofit media organization, our operations depend on the support of readers like you. Help us continue to deliver quality journalism that holds leaders accountable. Your support of our work at any level is important. In return, we promise our coverage will be understandable, influential, vigilant, solution-oriented, and fair-minded. Together we can make a difference.
View Comments
Dr. Khan states,
“Two recent papers, Worobey et al. and Pekar et al., present geospacial analysis of animal stalls in the Huanan market and viral phylogenetic analysis but do not provide convincing evidence of natural spillover. The data and analyses discussed by Worobey are equally consistent with both hypotheses: (1) that SARS-CoV-2 first entered humans at the Huanan Seafood Market in Wuhan, and (2) that SARS-CoV-2 first entered humans at another location”
Dr. Khan references the papers,
1) ‘Surveillance of SARS-CoV-2 in the environment and animal samples of the Huanan Seafood Market’, by George Gao, William Liu, and many others, Chinese Academy of Sciences, National Institute for Viral Disease Control and Prevention, and others https://assets.researchsquare.com/files/rs-1370392/v1_covered.pdf?c=1645813311
(2) ‘The Huanan market was the epicenter of SARS-CoV-2 emergence’, by https://zenodo.org/record/6299116#.Yh_ErJhMFdh, by Michael Worobey, Joshua Levy, Pekar, and others,
(3) ‘SARS-CoV-2 emergence very likely resulted from at least two zoonotic events’, by Pekar, Jonathan, Magee, Andrew, Parker, Edyth, and others, https://zenodo.org/record/6291628#.Yh_HPphMFdg
The main conclusion from the Worobey article that I observed was,
“Combining these findings with the collection of evidence we report here, including that both lineages show a strong geographical association with the Huanan market early in the Wuhan epidemic, allows us to conclude that multiple origins of SARS-CoV-2 most likely occurred specifically within the Huanan market, beginning in November 2019, and perhaps extending into December.”
Worobey finding possible ‘multiple origins’ for SARS-Cov-2 in the Huanan Seafood market (article #2 above), is consistent with the Pekar findings (article #3 above) that there were possible ‘multiple origins’ for SARS-Cov-2 on the world stage.
“we demonstrate that no virus transitional between lineages A and B has been sampled in humans. Our phylodynamic inference indicates the MRCA of SARS-CoV-2 was either the lineage A, lineage B, or a transitional C/C haplotype. However, our epidemic simulations show that a single zoonotic introduction of any of these plausible ancestral haplotypes is unlikely to produce the two large phylogenetic polytomies separated by two mutations that characterize lineages A and B. Neither a lineage A, lineage B, or C/C haplotype represents the root of SARS-COV-2 because there are likely at least two and perhaps many more origins of SARS-COV-2, each with its own distinct root.”
This quote is from the Pekar article # 3 above. That there may be ‘many origins’ to SARS-Cov-2. Pekar is referring to the unexplained C/C haplotypes that occurred early in the pandemic, that are neither A nor B variant, but are at the same phylogenic level as the A and B variants. There were as least 70 C/C variants, which the Pekar study group would like to label as sequencing errors. Figure S2 in the Pekar article (#3 above) shows many of those C/C variants in a phylogenic tree.
For the first time, we see notable virologists such as Pekar and Worobey share this ‘multiple origins’ of SARS-Cov-2 together, with Rambaut, Holmes, Andersen, and others.
Worobey made the following statement regarding frozen foods in his article,
“Finally, in another stall we identified as involved in the sale of live animals, a positive sample was obtained from inside a freezer
(Figs. 4A, S16 and Table S2).”
Whether Worobey’s assessment is accurate regarding the data provided in his article, Worobey may join the group that says frozen foods was the cause for SARS-Cov2, since no live animals tested positive for SARS-Cov-2. The WHO stated (in February 2021) regarding frozen foods in the Huanan Seafood market,
“16/87 (18.4%) of vendors selling cold-chain products were positive (95% CI: 10.9-28.1%) while five did not;
3) Type of goods dealt by environmental positive stalls
Analyses show that 60% (44/73) of the positive samples are related to 21 stalls, 19 of which were located in the western part of the Huanan market, and the remaining two stalls were located in the eastern part. 16 stalls were dealing with cold-chain product.”
‘WHO-convened Global Study of Origins of SARS-CoV-2’, https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part
So rather than a live animal origin of SARS-Cov-2, scientists may turn to a frozen foods origin of Covid-19. But the fact that most of the Covid-19 found in the Huanan Seafood market was in the sewage drainage, and possible multiple sources of origin for SARS-Cov-2, may portend against frozen food origin.
The second important aspect of the Worobey article is that he lists all the Environmental samples from the Huanan market in his Table S2. The WHO report didn’t have access to that data in February 2021. George Gao also lists all off the environmental samples from the Huanan Seafood Market, in Table 1 of his article mentioned above. Up to this point, only five environmental samples had been made available.