SARS-CoV-2 origin is still unknown

Abstract

Comments about Worobey, M., Levy, J. I., Malpica Serrano, L., Crits-Christoph, A., Pekar, J. E., Goldstein, S. A., ... & Andersen, K. G. (2022). The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, 377(6609), 951-959.
These comments can also be found as an eLetter at the bottom of the Science article web page.

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SARS-CoV-2 origin is still unknown
28 October 2022
eLetter visible at: https://www.science.org/doi/10.1126/science.abp8715
Virginie Courtier-Orgogozo*,virginie.courtier@ijm.fr, CNRS Research Director, Institut
Jacques Monod, Université Paris Cité, CNRS, Paris, France
Rahul A. Bahulikar, bahulikar@gmail.com, Scientist (Plant genetics and taxonomy expert),
BAIF Development Research Foundation, Pune, India
Colin D. Butler, colin.butler1955@gmail.com, Honorary Professor, Australian National
University, Canberra, Australia
Jean-Michel Claverie, jean-michel.claverie@igs.cnrs-mrs.fr, Virologist, Emeritus Professor
of Public Health, Aix-Marseille University, France
Etienne Decroly, etienne.decroly@univ-amu.fr, Aix-Marseille University, France
Joseph P. Dudley, joseph.p.dudley@leidos.com, Leidos Inc and University of Alaska
Fairbanks, USA
Richard H. Ebright, ebright@waksman.rutgers.edu, Professor of Chemistry and Chemical
Biology, Rutgers University, USA
François Graner, francois.graner@univ-paris-diderot.fr, biophysicist, Research Director,
Université Paris Cité, CNRS, Paris, France
Hideki Kakeya, kake@iit.tsukuba.ac.jp, Information Scientist, Associate Professor,
University of Tsukuba, Japan
Bernd Kaina, kaina@uni-mainz.de, Mainz University, Germany
Milton Leitenberg, MLEITENBERG@CS.COM, Senior Research Fellow, University of
Maryland, School of Public Affairs, USA
Serge Morand, serge.morand@umontpellier.fr, Montpellier University, CNRS
Nikolai Petrovsky, nikolai.petrovsky@flinders.edu.au, Professor of Medicine, Flinders
University, Vaxine Pty Ltd., Adelaide, Australia
Monali C. Rahalkar, monalirahalkar@aripune.org, Scientist (Microbiologist), Agharkar
Research Institute, Pune, India
Günter Theißen, guenter.theissen@uni-jena.de, Geneticist, Professor, Friedrich Schiller
University, Jena, Germany
* Corresponding author.
Email: virginie.courtier@normalesup.org.
In their recent article, Worobey et al. [1] confirm that the Huanan market served as an early
superspreading event for COVID-19, but provide no definitive evidence that SARS-CoV-2
was first transmitted to humans from wildlife sold there. Out of the 457 animals (18 species)
tested from the market, all were negative [2].
Although Worobey et al. date the first potential market-associated case to November 2019,
wastewater surveillance and retrospective analysis of human samples raise the possibility
that the virus may have been spreading in France, Brazil and Italy in September-November
2019 [3]. Details about the first official human cases unconnected to the market are still
unclear [4–6].
Worobey et al. examine SARS-CoV-2 positive environmental samples at the market,
collected in January 2020 [2]. These samples are probably of human origin because the
corresponding published sequences are identical to the ones found in patients [2]. Since the

earliest detected cases at the market occupied stalls too dispersed for their direct
contamination from 1-2 animal sources [7] and appear to be due to human-to-human
transmissions outside of stalls, analysis of spatial distribution of positive samples is not
relevant to infer the place of the first animal contamination. In fact, what the Worobey et al.
density risk map may locate is the epicenter of a superspreading event, an area in the
market’s southwest where public toilets and a closed Mahjong room are found.
The distribution of human positive cases at the market is consistent with both a zoonotic
introduction that would have occurred several weeks before the first cases were detected,
and an introduction of the virus to the market by an externally infected person.
Worobey et al. situate the epicenter of earliest cases to a district that also includes the
Wuhan Center for Disease Control laboratory, which conducts field and laboratory research
on bat viruses [8] and which moved into a new location only 500 meters from the market on
2 December 2019, something they do not mention. The authors do not consider the
possibility that this laboratory could be the site of the initial human case, but acknowledge
that “upstream events” and “exact circumstances” remain “obscure”.
Although it may be challenging to distinguish an accidental infection during laboratory or field
work from one that occurred between an animal and a market vendor, retrospective analyses
of 2019 human samples available inside and outside China could prove informative to
uncover upstream events.
In summary, the Huanan market can be considered as the epicenter of an early
superspreader event but it is not possible to conclude that it was the entry point of
SARS-CoV-2 into the human population. It is not yet clear how exactly SARS-CoV-2
originated. All hypotheses need to be investigated, including the possibility of a lab accident,
as recently summarized in the SAGO committee report [9] and in the Lancet commission
report [10].
Footnotes
The views expressed here are those of the authors and not necessarily those of their
respective institutions.
VCO and FG received funding from the "Who I am?" Labex to elucidate the proximal origins
of the SARS-CoV-2 virus.
CDB has received a writer's fee from the United Nations Environment Programme for the
forthcoming report "Covid-19: a warning".
RHE has received consulting fees on SARS-CoV-2 and the COVID-19 pandemic and
receives funding from the National Institutes of Health and Janssen under grants and
contracts unrelated to SARS-CoV-2 and the COVID-19 pandemic.
NP receives funding from the National Institutes of Health for vaccine research including
COVID-19.
Competing interests for RAB, JMC, ED, JPD, HK, BK, ML, SM, MR, GT, NP: None declared.

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