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COVID Origins: Worobey et al 2022 and Pekar et al 2022 Retraction Request

June 2024

Authors:

Colin D Butler

Australian National University

Gilles Demaneuf

Engineer and Data Scientist

Show all 33 authorsHide

This post is the third in a series of documented calls for the retraction of scientifically unsound papers on the origin of COVID-19. These papers are based on invalid premises and conclusions, or are potentially products of scientific misconduct — including fraud. Below is a letter requesting the retraction of "The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic" by Worobey et al. and “The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2” by Pekar et al., published on July 26, 2022, in Science.

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COVID Origins: Worobey et al 2022 and Pekar et al 2022 Retraction Request

Request for editorial action for Worobey et al. 2022 and Pekar et al. 2022 (June 14, 2024)

BIOSAFETY NOW, https://biosafetynow.substack.com/p/covid-origins-worobey-et-al-2022

June 14, 2024

This post is the third in a series of documented calls for the retraction of scientifically unsound

papers on the origin of COVID-19. These papers are based on invalid premises and conclusions, or are

potentially products of scientific misconduct — including fraud.

Below is a letter requesting the retraction of "The Huanan Seafood Wholesale Market in Wuhan was

the early epicenter of the COVID-19 pandemic" by Worobey et al. (1) and “The molecular

epidemiology of multiple zoonotic origins of SARS-CoV-2” by Pekar et al., (2) published on July 26,

2022, in Science. This letter was sent to the editor in chief of Science on June 14, 2024.

Subject: Request for editorial action on Worobey et al. 2022 and Pekar et al. 2022

Dear Editors:

We are writing to bring to your attention serious issues with a pair of papers published on July 26,

2022: "The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19

pandemic" by Worobey et al. (1) and “The molecular epidemiology of multiple zoonotic origins of

SARS-CoV-2” by Pekar et al. (2).

The analyses of Worobey et al. 2022 and Pekar et al. 2022 are unsound.

Worobey et al. (1) presents a geospatial analysis that purportedly suggests SARS-CoV-2 entered

humans at the Huanan Seafood Market in Wuhan.

The analyses in Worobey et al. are scientifically unsound (3-5). Zhang et al. 2022 point out intra-

market differences in the locations of animal cages and the locations of environmental samples

positive for SARS-CoV-2 that invalidate the conclusions of Worobey et al. 2022 (3). Weissman 2024

points out that ascertainment bias invalidates the conclusions of Worobey et al. (4). Stoyan and Chiu,

2024 point out that the statistical analyses in Worobey et al. are unsound (5).

Science has published a correction and an erratum to Worobey et al. 2022 (6). However, the

correction and erratum do not address the criticisms of refs. 3-5.

Pekar et al. 2022 (2), which was published together with Worobey et al. by an overlapping set of

authors, presents a phylogenomic analysis that purportedly suggests SARS-CoV-2 entered humans at

the Huanan Seafood Market in Wuhan.

The analyses of Pekar et al. 2022 are scientifically unsound (7-9). Massey et al. 2023 point out that

the unwarranted exclusion of intermediate sequences invalidates the conclusions of Pekar et al. (7).

Lv et al. 2024 report new intermediate sequences that invalidate the conclusions of Pekar et al. (8).

PubPeer comments report computational errors that invalidate--in toto--the conclusions of Pekar et

al. (9).

Science has published an erratum to Pekar et al. 2022 (10). However, the erratum does not address

the full set of criticisms of ref. 9 and does not address the criticisms of refs. 7-8.

The premises of Worobey et al. 2022 and Pekar et al. 2022 are unsound.

Phylogenomic evidence, epidemiological evidence, and documentary evidence all indicate that SARS-

CoV-2 entered humans in July-November 2019 (11-26 [entry in July-November 2019 in ref. 11; entry

in August 2019 in refs. 12-13; entry in September-October 2019 in ref. 14; entry in September-

November 2019 in ref. 15; entry in September 2019 in ref. 16; entry in October-November in ref. 17;

and entry in or before November 2019 in refs. 18-26]). Arguments based on data for the Huanan

Seafood Market on or after mid- to late December 2019--as in Worobey et al. 2022 and Pekar et al.

2022--cannot, even in principle, shed light on spillover into humans that occurred one to five months

earlier, in July-November, 2019.

Worobey et al. 2022 and Pekar et al. 2022 may be products of scientific misconduct, up to and

including scientific fraud.

Compelling evidence has been presented that four of the authors of Worobey et al. 2022 and Pekar

et al. 2022 (Kristian Andersen, Robert Garry, Edward Holmes, and Andrew Rambaut), including one of

the corresponding authors of Worobey et al. 2022 and Pekar et al. 2022 (Kristian Andersen),

committed scientific misconduct, publishing conclusions they knew to be invalid, on a previous paper

on the same subject: Andersen et al. 2020 (27), a paper that concluded "Our analyses clearly show

that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus" and "we do not

believe that any type of laboratory-based scenario is plausible."

Private email and Slack communications of authors Andersen, Garry, Holmes, and Rambaut--made

public through a Congressional inquiry--establish that Andersen, Garry, Holmes, and Rambaut knew

the premises and conclusions of their paper were invalid at the time the paper was drafted, at the

time the paper was submitted for publication, and even at the time the paper was published (28-29).

For example, in private email and Slack communications, Andersen wrote "the lab escape version of

this is so friggin' likely to have happened because they were already doing this type of work and the

molecular data is fully consistent with that scenario" on the day the first draft of the paper was

started; wrote "accidental escape is in fact highly likely" and "we can’t prove one way or the other,

but we never will be able to" on the next day; wrote "From a genomics perspective, the theories

Richard Ebright lay out I expect would look the same - there would be no way to distinguish between

them" four days later; wrote "The furin link keeps bugging me" on the day the first draft of the paper

was completed; wrote "we unfortunately just can’t rule out a potential accidental infection from the

lab" on the day the paper was submitted for publication; and wrote "we can’t fully disprove culture"

and "We also can’t fully rule out engineering" a month after publication of the paper (28-29).

Formal requests for retraction of Andersen et al. 2020 for scientific misconduct have been submitted

(30).

When papers are scientifically unsound, have invalid premises and conclusions, and have four

authors, including a corresponding author, who committed scientific misconduct on a previous paper

on the same subject--as for Worobey et al. 2022 and Pekar et al. 2022--there is clear basis to infer

the papers may be products of scientific misconduct, up to and including fraud.

In conclusion, Worobey et al. 2022 and Pekar et al. 2022 are scientifically unsound, have invalid

premises and conclusions, and may be products of scientific misconduct, up to and including

scientific fraud. We urge Science to issue an Expression of Editorial Concern for these papers and to

initiate an investigation of these papers for possible retraction.

Signers (in alphabetical order)

Paul Babitzke, Penn State University

Jay Bhattacharya, Stanford University

Colin Butler, Australian National University

Gilles Demaneuf, Engineer and Data Scientist, New Zealand

Richard H. Ebright, Rutgers University

Mohamed E. El Zowalaty, Ahram Canadian University

Andre Goffinet, UC Louvain

Richard N. Goldstein, Harvard University

Edward Hammond, ex Sunshine Project

Neil Harrison, Columbia University

Angelika Hilbeck, ex Swiss Federal Institute of Technology

Laura H. Kahn, One Health Initiative

Hideki Kakeya, University of Tsukuba

Steven Lagana, Columbia University

Yanna Lambrinidou, Virginia Tech

Jonathan R. Latham, Bioscience Resource Project

Milton Leitenberg, University of Maryland

Austin Lin, State University of New York

Steven E. Massey, University of Puerto Rico - Rio Piedras

Tony R. Merriman, University of Alabama at Birmingham

Jamie Metzl, Atlantic Council

Stuart A. Newman, New York Medical College

Bryce E. Nickels, Rutgers University

Andrew Noymer, University of California, Irvine

Matt Ridley, ex Science and Technology Select Committee, UK House of Lords.

Steven Quay, ex Stanford University School of Medicine

Joe Schaefer, SunStar Systems

Harish Seshadri, Indian Institute of Science

Diederick Sprangers, ENSSER

Günter Theißen, Friedrich Schiller University Jena

Antonius M. VanDongen, Duke University

Roland Wiesendanger, University of Hamburg

Allison K. Wilson, Bioscience Resource Project

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Unwarranted Exclusion of Intermediate Lineage A-B SARS-CoV-2 Genomes Is Inconsistent with the Two-Spillover Hypothesis of the Origin of COVID-19

Article

Full-text available

Mar 2023
Microbiol Res

Pekar et al. (2022) propose that SARS-CoV-2 was a zoonotic spillover that first infected humans in the Huanan Seafood Market in Wuhan, China. They propose that there were two separate spillovers of the closely related lineages A and lineage B in a short period of time. The two lineages are differentiated by two SNVs; hence, a single-SNV A-B intermediate must have occurred in an unsampled animal host if the two-spillover hypothesis is correct. Consequently, confirmation of the existence of an intermediate A-B genome from humans would falsify their hypothesis of two spillovers. Pekar et al. identified and excluded 20 A-B intermediate genomes from their analysis. A variety of exclusion criteria were applied, including low read depth and the assertion of repeated erroneous base calls at lineage-defining positions 8782 and 28144. However, data from GISAID show that most of the genomes were sequenced to high average sequencing depth, appearing inconsistent with these criteria. The decision to exclude the majority of genomes was based on personal communications, with raw data unavailable for inspection. Multiple errors, biases, and inconsistencies were observed in the exclusion process. For example, 12 intermediate genomes from one study were excluded; however, 54 other genomes from the same study were included, indicating selection bias. Puzzlingly, two intermediate genomes from Beijing were discarded despite an average sequencing depth of 2175X; however, four genomes from the same sequencing study were included in the analysis. Lastly, we discuss 14 additional possible intermediate genomes not discussed by Pekar et al. and note that genome sequence filtration is inappropriate when considering the presence or absence of a specific SNV pair in an outbreak. Consequently, we find that the exclusion of many of the intermediate genomes is unfounded, leaving the conclusion of two natural zoonoses unsupported.

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Article

Full-text available

Jul 2022

Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic

Article

Full-text available

Jul 2022

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports but later this conclusion became controversial. We show the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.

Dating the Common Ancestor from an NCBI Tree of 83688 High-Quality and Full-Length SARS-CoV-2 Genomes

Article

Full-text available

Sep 2021

Xuhua Xia

All dating studies involving SARS-CoV-2 are problematic. Previous studies have dated the most recent common ancestor (MRCA) between SARS-CoV-2 and its close relatives from bats and pangolins. However, the evolutionary rate thus derived is expected to differ from the rate estimated from sequence divergence of SARS-CoV-2 lineages. Here, I present dating results for the first time from a large phylogenetic tree with 86,582 high-quality full-length SARS-CoV-2 genomes. The tree contains 83,688 genomes with full specification of collection time. Such a large tree spanning a period of about 1.5 years offers an excellent opportunity for dating the MRCA of the sampled SARS-CoV-2 genomes. The MRCA is dated 16 August 2019, with the evolutionary rate estimated to be 0.05526 mutations/genome/day. The Pearson correlation coefficient (r) between the root-to-tip distance (D) and the collection time (T) is 0.86295. The NCBI tree also includes 10 SARS-CoV-2 genomes isolated from cats, collected over roughly the same time span as human COVID-19 infection. The MRCA from these cat-derived SARS-CoV-2 is dated 30 July 2019, with r = 0.98464. While the dating method is well known, I have included detailed illustrations so that anyone can repeat the analysis and obtain the same dating results. With 16 August 2019 as the date of the MRCA of sampled SARS-CoV-2 genomes, archived samples from respiratory or digestive tracts collected around or before 16 August 2019, or those that are not descendants of the existing SARS-CoV-2 lineages, should be particularly valuable for tracing the origin of SARS-CoV-2.

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

Article

Full-text available

May 2021

Global sequencing of hundreds of thousands of genomes of Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, has continued to reveal new genetic variants that are the key to unraveling its early evolutionary history and tracking its global spread over time. Here, we present the heretofore cryptic mutational history and spatiotemporal dynamics of SARS-CoV-2 from an analysis of thousands of high-quality genomes. We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the USA harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains, which have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic in 2020. There have been multiple replacements of predominant coronavirus strains in Europe and Asia and the continued presence of multiple high-frequency strains in Asia and North America. We have developed a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).

Timing the SARS-CoV-2 index case in Hubei province

Article

Full-text available

Mar 2021

Backtracking a pandemic Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have had a history of abortive human infections before a variant established a productive enough infection to create a transmission chain with pandemic potential. Therefore, the Wuhan cluster of infections identified in late December of 2019 may not have represented the initiating event. Pekar et al. used genome data collected from the early cases of the COVID-19 pandemic combined with molecular clock inference and epidemiological simulation to estimate when the most successful variant gained a foothold in humans. This analysis pushes human-to-human transmission back to mid-October to mid-November of 2019 in Hubei Province, China, with a likely short interval before epidemic transmission was initiated. Science , this issue p. 412

Evolutionary trajectory of diverse SARS-CoV-2 variants at the beginning of COVID-19 outbreak

Article

Mar 2024

Despite extensive scientific efforts directed toward the evolutionary trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans at the beginning of the COVID-19 epidemic, it remains unclear how the virus jumped into and evolved in humans so far. Herein, we recruited almost all adult coronavirus disease 2019 (COVID-19) cases appeared locally or imported from abroad during the first 8 months of the outbreak in Shanghai. From these patients, SARS-CoV-2 genomes occupying the important phylogenetic positions in the virus phylogeny were recovered. Phylogenetic and mutational landscape analyses of viral genomes recovered here and those collected in and outside of China revealed that all known SARS-CoV-2 variants exhibited the evolutionary continuity despite the co-circulation of multiple lineages during the early period of the epidemic. Various mutations have driven the rapid SARS-CoV-2 diversification, and some of them favor its better adaptation and circulation in humans, which may have determined the waxing and waning of various lineages.

Proximity ascertainment bias in early COVID case locations

Article

Mar 2024

Michael B Weissman

A comparison of the distances to the Huanan Seafood Market of early COVID cases with known links to the market versus cases without known links shows results apparently incompatible with a location model lacking proximity ascertainment bias. The sign of the difference instead agrees with a model in which such ascertainment bias is large. In the presence of such bias inferences based on the clustering of case locations become unreliable.

Statistics did not prove that the Huanan Seafood Wholesale Market was the early epicentre of the COVID-19 pandemic

Article

Jan 2024

In a recent prominent study, Worobey et al. (2022. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, 377(6609), 951–959) purported to demonstrate statistically that the Huanan Seafood Wholesale Market was the epicentre of the early COVID-19 epidemic. 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.

Phylogenetic reconstruction of the initial stages of the spread of the SARS-CoV-2 virus in the Eurasian and American continents by analysing genomic data

Article

Aug 2021
VIRUS RES

Samples from complete genomes of SARS-CoV-2 isolated during the first wave (December 2019 - July 2020) of the global COVID-19 pandemic from 21 countries (Asia, Europe, Middle East and America) around the world, were analysed using the phylogenetic method with molecular clock dating. Results showed that the first cases of COVID-19 in the human population appeared in the period between July and November 2019 in China. The spread of the virus into other countries of the world began in the autumn of 2019. In mid-February 2020, the virus appeared in all the countries we analysed. During this time, the global population of SARS-CoV-2 was characterized by low levels of the genetic polymorphism, making it difficult to accurately assess the pathways of infection. The rate of evolution of the coding region of the SARS-CoV-2 genome equal to 7.3 × 10⁻⁴ (5.95 × 10⁻⁴ - 8.68 × 10⁻⁴) nucleotide substitutions per site per year is comparable to those of other human RNA viruses (Measles morbillivirus, Rubella virus, Enterovirus C). SARS-CoV-2 was separated from its known close relative, the bat coronavirus RaTG13 of the genus Betacoronavirus, approximately 15-43 years ago (the end of the 20th century).