Covid-19

SARS-CoV-2: new report calls for further investigation of the lab-origin hypothesis

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The Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) has submitted its first preliminary report to the World Health Organisation (WHO) and has called for further investigation of the hypothesis that SARS-CoV-2 leaked from a laboratory.

Twenty-four of the 27 SAGO members agreed that it remained important “to consider all reasonable scientific data that is available either through published or other official sources to evaluate the possibility of the introduction of SARS-CoV-2 into the human population through a laboratory incident”.

The SAGO, which includes molecular biologists, veterinarians, clinical doctors, and experts in ecology, has recommended that genomic and molecular epidemiological investigations should be carried out and that the following two possibilities should be assessed:

  • the possibility that SARS-CoV-2 was introduced to the human population via an animal or environmental spillover event, and
  • the possibility that the virus was introduced to the human population “through a breach in biosafety and biosecurity measures through a laboratory incident”.

The group said no new data had been made available “to evaluate the laboratory as a pathway of SARS-CoV-2 into the human population” and recommended further investigations into this and all other possible pathways.

“The SAGO will remain open to any and all scientific evidence that becomes available in the future to allow for comprehensive testing of all reasonable hypotheses,” the group said.

The group said in its report: “To support biosafety and biosecurity investigations into the introduction of SARS-CoV-2 into the human population through a laboratory incident; the SAGO notes that there would need to be access to and review of the evidence of all laboratory activities (both in vitro and in vivo studies) with coronaviruses including SARS-CoV-2-related viruses or close ancestors and the laboratory’s approach to implementation and improvement of laboratory biosafety and biosecurity.”

It added: “As it is not common practice to publish the institutional implementation of biosafety and biosecurity practices of individual laboratories in peer-reviewed scientific journals, additional information will need to be obtained and reviewed to make conclusive recommendations.”

In a footnote to the report it was noted that three members of the SAGO – Vladimir Dedkov, Carlos Morel, and Yungui Yang – did not agree with the inclusion in the preliminary report of a recommendation for further studies evaluating the possibility that SARS-CoV-2 was introduced to the human population through a laboratory incident.

It was stated in the footnote that, from the viewpoint of Dedkov, Morel, and Yang, there was no new scientific evidence to question the conclusion of the WHO-convened global study of the origins of SARS-CoV-2 published in March 2021.

The SAGO mission is separate from the one conducted in Wuhan from January 14 to February 10, 2021, by an international team comprising 17 Chinese members and 17 experts from other countries, the WHO, the Global Outbreak Alert and Response Network (GOARN), and the World Organisation for Animal Health (OIE).

The SAGO members did not visit Wuhan to produce their preliminary report.

Six members of the SAGO team – John Watson, Thea Fischer, Hung Nguyen-Viet, Vladimir Dedkov, Farag El Moubasher, and Yang Yungui – were involved in the 2021 WHO-China mission.

Marion Koopmans, who was on the WHO-China mission to Wuhan was in the initial list of SAGO members published on October 13, 2021, but was not included in the final selection of members.

The report produced by participants in the WHO-China mission was widely condemned as a whitewash.

The main messages of the WHO-China report were that a lab origin is “extremely unlikely” and that the virus most likely spread naturally, either directly from an animal to humans or via an intermediate host.

China’s Foreign Ministry spokesperson, Zhao Lijian, said on June 10 that the lab leak theory was “a false claim concocted by anti-China forces for political purposes”. It has nothing to do with science, Zhao said.

“The Chinese side has invited WHO experts to visit the Wuhan lab, and the joint report reached the clear conclusion that ‘a laboratory origin of the pandemic was considered to be extremely unlikely’,” Zhao added.

“Since the SAGO report has called for investigation into biological laboratories ‘located worldwide where early Covid-19 cases have been retrospectively detected’ for the next phase of study, investigation should first target highly suspicious laboratories such as those at Fort Detrick and the University of North Carolina in the US.”

Zhao said that, after the WHO established the SAGO, China recommended experts to join the group and organised events for Chinese experts to share research findings with the WHO Secretariat and the SAGO.

“China is the only country that has invited more than once WHO expert groups to come into the country to conduct joint SARS-CoV-2 origins study,” Zhao said.

“It is also the only country that has provided multiple opportunities for its experts to share progress on origins tracing with SAGO. China has shared more data and research findings on SARS-CoV-2 origins study than any other country.”

Biosafety and biosecurity

The SAGO says that additional investigations should be carried out with lab staff tasked with managing and implementing biosafety and biosecurity at laboratories, i.e. those in the proximity of the original Covid-19 outbreak working with SARS-like viruses in Wuhan, and potentially with those located worldwide where early Covid-19 cases have been retrospectively detected before 2020.

This, the SAGO says, “would provide an opportunity for more specific questions to be asked related to biosafety and biosecurity management of SARS-like virus studies at the individual laboratories”.

It would also provide an opportunity for staff and scientists “to give their perspective on the possibility of a laboratory incident and whether any occupational illnesses occurred before the recognised start of the pandemic”.

The SAGO also recommends that, in the area where the first cases of SARS-CoV-2 infection were reported in China, there should be an examination of regulatory biosafety or biocontainment standards and biocontainment levels and risk-mitigation strategies for SARS-like CoV-associated studies.

“These considerations should include discussions with those responsible for administering biosafety and biosecurity,” the SAGO says.

Investigators should also determine the occupational hazards intrinsic to laboratories working with SARS-like CoV and the nature of the studies performed before the first reported Covid-19 cases in Wuhan “and whether they involved reverse engineering or gain-of-function, genetic manipulation or animal studies with strains of SARS-like CoV”.

The SAGO further recommends the following:

  • that investigators work on determining the risks associated with field-related activities, such as the collection of specimens from bats or other wildlife sources and the potential for SARS-like CoV infection of staff;
  • that they evaluate potential scenarios where a breakdown in biosafety or biosecurity procedures led to a possible laboratory-acquired infection with the studied pathogen; and
  • that they determine if there were any reported biocontainment breaches or laboratory incidents or accidents with SARS-like coronaviruses in biosafety level (BSL2/3/4) laboratories that may have resulted in escape and/or infection of staff members prior to December 2019 where early cases were detected in China.

There is a continued need for the identification and regulation of high-risk pathogen manipulation studies including gain of function and dual use research of concern, the SAGO says.

The SAGO proposes the following:

  • a review of existing legislation and consideration of better national/institutional governance of complex experiments,
  • investigations of viruses with zoonotic potential being studied in an individual laboratory or programme of work,
  • investigations of biosafety programme management, and
  • identification, regulation, and education on matters of reverse genetics and gain of function of pathogens.

In relation to the possibility that SARS-CoV-2 was introduced to the human population via an animal or environmental spillover event, the SAGO recommends a lengthy list of studies that it says need to be carried out.

“Studies must include direct and indirect interface with wild animals, direct interface with domestic animals infected with pathogens from wild or domestic animals and chains of transmission between ancestral hosts and intermediate species,” the SAGO says.

The group says that increased surveillance of wildlife is needed globally where SARS-like viruses were detected in bats “as well as susceptible species detected through reverse zoonoses to detect potential current and future animal reservoirs”.

The SAGO points out that, so far, neither the SARS-CoV-2 virus progenitors nor the natural/intermediate hosts or spillover event to humans have been identified.

‘Scientific work should be separate from politics’

The WHO’s director-general, Tedros Adhanom Ghebreyesus, said in a speech to member states on June 9 that understanding the origins of SARS-CoV-2 was very important scientifically, to prevent future epidemics and pandemics.

“But morally, we also owe it to all those who have suffered and died, and their families,” Tedros said. “The longer it takes, the harder it becomes. We need to speed up, and act with a sense of urgency.

“All hypotheses must remain on the table until we have evidence that enables us to rule certain hypotheses in or out. This make it all the more urgent that this scientific work be kept separate from politics.”

The way to prevent politicisation, Tedros said, was for countries to share data and samples, with transparency, and without interference from any government.

“The only way this scientific work can progress successfully is with full collaboration from all countries, including China, where the first cases of SARS-CoV-2 were reported,” he said.

Calls for new analyses

There is new information in the SAGO report about blood samples that were stored in Wuhan.

The SAGO team says that additional studies of potential cases of SARS-CoV-2 infection in 2019 in Wuhan are needed from China “and should include a further review, including analyses of clinical and demographic characteristics and risk factors among the initial 174 human cases identified in China”.

The team also recommends that investigators explore the availability of human samples collected in the months running up to the emergence of SARS-CoV-2 in other health programmes (e.g. polio and measles surveillance) in China as well as in public health entities in other parts of the world and says these samples should be tested for SARS-CoV-2 presence through PCR or serological testing.

SAGO reports that the group was presented with new, unpublished serologic results obtained by Chinese scientists that relate to more than 40,000 stored samples from blood donors in Wuhan who provided blood between September and December 2019.

“These samples were reported to have been tested for antibodies to SARS-CoV-2,” the SAGO reports. “More than 200 samples proved positive (by ELISA), however, none were positive upon using a confirmative assay (by serum neutralization assays).”

The SAGO reports that other samples collected in Wuhan prior to December 2019 were reported to be negative on retrospective serological testing.

The group has requested further information about these data and the methods used to analyse the samples.

The SAGO also recommends a fresh assessment of 76,000 patients in Wuhan and their potential link to the early days of the Covid-19 pandemic.

The group notes that an initial high-level review was presented to the WHO-China mission team. This included a study of more than 76,000 patients who presented to 233 health institutions in Wuhan in the months before the recognised outbreak of Covid-19 in December 2019.

“The results presented to the WHO mission team visiting China in January– February 2021 suggest that none of the 76,000 patients were compatible with Covid-19,” the SAGO says in its report.

“As was suggested in the Joint Report, the SAGO recommends more work needs to be done to evaluate the criteria used to disregard these 76,000 as SARS-CoV-2 cases.”

The SAGO members note that the SARS-CoV-2 case definition was initially very stringent during the first review.

“This likely resulted in many asymptomatic, mild to moderate Covid-19 cases being missed,” the group states.

The group notes that, in 2021, the joint WHO-China team recommended that there should be a further review of the methods used to identify and characterise the initial patients in the retrospective clinical search for patients presenting with relevant conditions to the 233 Wuhan medical institutions, in order to search for features, such as clustering, that could be suggestive of the occurrence of previously unrecognised cases of SARS-CoV-2 infection.

The WHO-China team agreed on a new, broader the SARS-CoV-2 case definition.

The SAGO team says in its report: “It is possible that the application of stringent clinical criteria, resulting in the identification of only 92 clinically compatible cases, may have decreased the possibility of identifying a group or groups of cases with milder illness.

“Furthermore, the possibility that earlier transmission of SARS-CoV-2 infection was occurring in this community cannot be excluded on the basis of this evidence or lack thereof.

“The SAGO renews this recommendation and suggests a further review is required to study these 76,000 patients and their potential link to the early days of the Covid-19 pandemic.

The SAGO team says that, based on data presented by invited Chinese scientists to the SAGO, “a descriptive review of surveillance data for influenza-like illness (ILI), pharmacy purchases and analyses of mortality data did not provide clear evidence of widespread circulation of SARS-CoV-2 before the recognised start in December 2019”.

The team says the SAGO is awaiting further details on the unexplained increase in ILI in adults from Wuhan in the 46th week of 2019, preceding increases seen in ILI in Wuhan in the 51st and 52nd weeks of 2019.

“Additional analytical approaches may be able to identify differences from expected normal patterns, including comparisons of data from different provinces in China and to previous years,” the SAGO team reports.

In its preliminary report, the SAGO says proposed topics for future meetings include:

  • further analysis of findings from studies pertaining to the Huanan market in Wuhan China and follow up on any identified leads,
  • global engagement with scientists working on SARS-like viruses in bats to seek input on the molecular biology and evolution of these viruses and to identify potential biosafety issues,
  • in-depth investigation of animals susceptible to SARS-CoV-2,
  • surveillance and retrospective testing of samples to identify the possible intermediate hosts and potential new animal reservoirs, and
  • studies about the origins of new variants, which would include collaboration with other experts working on genomic surveillance, wastewater surveillance, and surveillance in immunosuppressed patients and potential animal reservoirs.

Reactions to the SAGO report

The SAGO report has been criticised on social media in such comments as “all the report contents are still based on the ‘studies’ provided to them by China, instead of any investigation on their own’ (tweet by @Daoyu15).

However, in a lengthy Twitter thread about the new report, @BillyBostickson, who is a member of the DRASTIC team of independent investigators said: “… it seems that SAGO acted with certain integrity in this investigation”.

Alina Chan, who is a postdoctoral fellow at the Broad Institute of MIT and Harvard in the US and co-author of the book Viral about the search for the origin of Covid-19,  tweeted: “ It’s been a long trek, but after 2.5 years we finally have US intel community, @WHO SAGO & Lancet Covid commission chair aligned in that both natural & lab #OriginOfCovid are plausible and must be investigated. All concur that key evidence is lacking.”

Jamie Metzl, who is a member of a WHO advisory committee on human genome editing, praised the WHO in the following tweet:

Metzl added: “The @WHO SAGO report on #COVID19 origins is an almost complete refutation of the Worobey et al claim of “dispositive evidence” of a market origin.”

He accused Zhao Lijian of “knowingly lying”.

Alina Chan called for clarity about bias and conflicts of interest.

She tweeted: “It’s good to see that SAGO is open to investigating both natural and lab origin hypotheses. However, based on their preliminary report and process so far, it is unclear to me how they are checking their biases and how feasible some of their suggested studies will be.”

She added:


Richard Ebright, who is a molecular biologist at Rutgers University in the US, tweeted: “Carlos Morel has a $1.2 B financial connection to entities that will be subjects or targets of any investigation of origins: Peter Daszak, Dennis Carroll, Jonna Mazet, George Gao, EcoHealth Alliance, PREDICT and GVP He must be required to recuse or, preferably, removed from SAGO.”

Chan also said on Twitter that SAGO was limited in the same ways that the 2021 international @WHO team sent to Wuhan was: “No access to raw data, records, and witnesses. No leverage to obtain access.”

She added: “SAGO continues to lay out super obvious routes of investigation that Chinese investigators would’ve known to do immediately after they detected the outbreak in 2019. How productive some of these inquiries will be 2.5 years later? Imo unlikely.”

She also tweeted the following:

When the WHO published the initial list of people proposed for SAGO membership, it said: “They are to serve in their personal capacities to represent the broad range of disciplines relevant to emerging and re-emerging pathogens.

“In evaluating the applications submitted, consideration was given to attaining an adequate distribution of technical expertise, geographical representation, and gender balance.”

The WHO had invited the public to submit comments about those selected for SAGO membership. On November 9, 2021, the organisation announced the addition of Gladys Kalema-Zikusoka and Normand Labbe to the original list of 26 proposed members.

There was criticism of the inclusion in the proposed list of Marion Koopmans and six other people involved in the January/February 2021 mission to Wuhan. Koopmans is considered to have a serious conflict of interest and to be too biased against the lab origin hypothesis to be included in the new advisory group. She has herself been involved in gain-of-function research.

Also, Christian Drosten was one of the signatories of the statement published in The Lancet in which suggestions that Covid-19 does not have a natural origin were condemned as “conspiracy theories”.

There were calls for the removal of Wacharapluesadee from the list because of an alleged conflict of interest (she is a subcontractor on an NIH grant to the EcoHealth Alliance) and for the removal of Kathrin Summermatter, who has described the lab origin hypothesis as insignificant speculation and a conspiracy theory.

U.S. Right to Know wrote a letter to the WHO in which it asks for ten of the proposed members of SAGO, including Drosten, Summermatter, and Koopmans, to be replaced because they did not meet the standards for SAGO membership.

“According to the WHO terms of reference, SAGO members ‘must be free of any real, potential, or apparent conflicts of interest,’ and ‘must respect the impartiality … required of WHO’,” U.S. Right to Know wrote.

The research group pointed out that Wacharapluesadee was a subcontractor on a 2020 multi-million-dollar NIH grant to the EcoHealth Alliance.

“Her lab at Chulalongkorn University is slated to receive a $1.07 million subcontract,” U.S. Right to Know wrote. “According to the EcoHealth Alliance, Dr Wacharapluesadee is a longstanding collaborator for ‘more than ten years’. Between 2014 and 2019, she was funded by a UC Davis USAID PREDICT 2 grant, in which the EcoHealth Alliance was deeply involved.

“Since 2013, Dr Wacharapluesadee has been a co-author on multiple publications with the EcoHealth Alliance, including four with its president, Dr Daszak.”

Anyone with personal, financial, or academic ties to the EcoHealth Alliance (including grant funding, co-authorship or other research collaboration) or to the Wuhan Institute of Virology, cannot be a SAGO member, U.S. Right to Know says, “because such ties could impair their judgment in an investigation of zoonotic and/or lab origins of SARS-CoV-2”. Any such ties constitute an impermissible conflict of interest, U.S. Right to Know says.

The research group says that Drosten’s prejudgement about the lab origin hypothesis is disqualifying.

“Moreover, Dr Drosten served on a bat conference advisory committee with the Ecohealth Alliance and Dr Zhengli Shi of the Wuhan Institute of Virology,” U.S. Right to Know wrote.

“Dr Drosten’s funding and continued research collaborations rest on the zoonotic potential of bat coronaviruses. For these reasons, Dr Drosten has a personal stake in SAGO’s outcome, because it is to his personal and professional advantage to declare a zoonotic origin for SARS-CoV-2. This, too, disqualifies him from being a SAGO member.”

Koopmans’ prejudgement about the lab origin hypothesis is also disqualifying, U.S. Right to Know says.

The research group points out that Erasmus University’s viroscience department puts the EcoHealth Alliance first on its list of collaborators.

“The disclosure also states that the viroscience department is ‘closely involved’ in the EcoHealth Alliance. This conflict of interest, too, is disqualifying,” U.S. Right to Know wrote. “Dr Koopman’s membership in the conflicted, discredited and failed Global Study of Origins of SARS-CoV-2 is also disqualifying.”

U.S Right to Know also called for Dedkov, El Moubasher, Fischer, Nguyen-Viet, Watson, and Yang to be replaced.

The research group said the proposed SAGO members did not include enough experts from the disciplines of biosafety, biosecurity, occupational health and safety, laboratory safety and security, ethics, and social sciences.

“Scientists from diverse fields of study, not merely infectious disease, should be included in SAGO for many reasons, including to offset any conflicts of interest from zoonotic origins infectious disease researchers,” U.S Right to Know wrote. “We urge WHO to add at least three additional members from these disciplines to SAGO.”

The research group proposed ten replacement SAGO members: Filippa Lentzos, Richard Ebright, Jesse Bloom, Alina Chan, David Relman, Alison Young, Edward Hammond, Milton Leitenberg, Stuart Newman, and Michael Antoniou.

SAGO members

  • Phillip Alviola, associate professor at the Animal Biology Division at the Institute of Biological Sciences, University of the Philippines.
  • Abdullah Assiri, Assistant Deputy Minister for Preventive Health at the Ministry of Health in Saudi Arabia.
  • Stuart Blacksell, professor of tropical microbiology at the Nuffield Department of Medicine at the University of Oxford.
  • Inger Damon, director of the Division of High Consequence Pathogens and Pathology at the CDC.
  • Vladimir Dedkov, deputy director for research at the Pasteur Institute in Russia.
  • Christian Drosten, professor and head of the Institute of Virology at the Charité university hospital in Germany.
  • Farag El Moubasher, senior infectious disease epidemiologist and head of the communicable diseases control programmes at the Ministry of Public Health in Qatar.
  • Thea Fischer, professor of virology at the University of Copenhagen and head of clinical research at the Nordsjaellands Hospital in Denmark.
  • Raman Gangakhedkar, the Dr C.G. Pandit National Chair at the Indian Council of Medical Research.
  • Nada Ghosn, head of the epidemiology surveillance programme and medical officer for the Directorate of Prevention at the Ministry of Health, Lebanon.
  • Maria Guzman, head of the Center for Research, Diagnostic and Reference at the Pedro Kourí National Institute of Tropical Medicine in Cuba.
  • Christian Happi, professor and director at the African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer’s University, Ede, Nigeria.
  • Gladys Kalema-Zikusoka, the founder and chief executive officer of Conservation Through Public Health, a nonprofit organisation based in Uganda and the US.
  • Normand Labbe, a biosafety inspector at the Public Health Agency of Canada.
  • Sowath Ly, deputy head of epidemiology and the public health unit at the Cambodian nonprofit research institution the Institut Pasteur du Cambodge.
  • Jean-Claude Manuguerra, research director of the Environment and Infectious Risks Unit and head of the Emergency Biological Intervention Unit at the Institut Pasteur in France.
  • Khin Myint, head of the Emerging Virus Research Unit at the Eijkman Institute for Molecular Biology in Jakarta, Indonesia.
  • Carlos M. Morel, director at the Center for Technological Development in Health at the Oswaldo Cruz Foundation (Fiocruz), which functions as a national institute of health for the Brazilian government.
  • Hung Nguyen-Viet, co-leader of the Animal and Human Health Programme at the International Livestock Research Institute in Kenya.
  • Chinwe Ochu, director of prevention programmes and knowledge management at the Nigeria Centre for Disease Control.
  • Masayuki Saijo, director of the medical planning department at the city health and welfare bureau in Sapporo, Japan.
  • Rosemary Sang, advisor and chief research officer at the Centre for Virus Research at the Kenya Medical Research Institute (KEMRI).
  • Kathrin Summermatter, head of the biosafety centre and managing director of the biosafety level 3 laboratory at the Institute for Infectious Diseases at the University of Berne in Switzerland.
  • Marietjie Venter, professor of the Zoonotic Arbovirus and Respiratory Virus Research Programme at the Centre for Viral Zoonoses in the Department of Medical Virology at the University of Pretoria in South Africa.
  • Supaporn Wacharapluesadee, researcher at the King Chulalongkorn Memorial Hospital and the Thai Red Cross Society and a committee member of the Chula School of Global Health at the Faculty of Medicine, Chulalongkorn University, Thailand.
  • John Watson, honorary professor at the Faculty of Epidemiology and Population Health at the London School of Hygiene and Tropical Medicine and visiting professor in the Research Department of Infection and Population Health at University College London.
  • Yungui Yang, deputy director at the Beijing Institute of Genomics at the Chinese Academy of Sciences.

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