Investigations into the origin of COVID-19

There are several ongoing efforts by scientists, governments, international organisations, and others to determine the origin of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Most scientists say that as with other pandemics in human history, the virus is likely of zoonotic origin in a natural setting, and ultimately originated from a bat-borne virus.[1][2][3][4][5][6][7] Many other explanations, including several conspiracy theories, have been proposed about the origins of the virus.[8][9][10] Some have speculated that SARS-CoV-2 was accidentally released from a laboratory, but there is no evidence for this, and it is considered much less likely than a natural origin.[11]

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SARS-CoV-2 has close genetic similarity to multiple previously identified bat coronaviruses, suggesting it crossed over into humans from bats.[4][12][13][14][15] Research is ongoing as to whether SARS-CoV-2 came directly from bats or indirectly through any intermediate hosts.[16][17] Initial genome sequences of the virus showed little genetic diversity, although subsequently a number of stable variants emerged (some spreading more vigorously), indicating that the spillover event introducing SARS-CoV-2 to humans is likely to have occurred in late 2019.[18][19] Health authorities and scientists internationally state that as with the 2002–2004 outbreak of SARS-1, efforts to trace the specific geographic and taxonomic origins of SARS-CoV-2 could take years, and the results could be inconclusive.[20]

In January 2021, the World Health Assembly (decision-making body of the World Health Organization (WHO)) commissioned a study on the origins of the virus, to be conducted jointly between WHO experts and Chinese scientists. In March 2021, the findings of this study were published online in a report to the WHO Commissioner-General.[1][21][22] Echoing the assessment of most virologists,[23][24][25] the report determined that the virus most likely had a zoonotic origin in bats, possibly transmitted through an intermediate host. It also stated that a laboratory origin for the virus was "extremely unlikely".[8][26]

Scientists found the conclusions of the WHO report to be helpful but noted that more work was needed.[27] In the United States, the European Union, and other countries, some criticised the lack of transparency and data access in the report's formulation.[28][29] The WHO issued its 30 March report alongside a statement of the WHO director-general Tedros Adhanom Ghebreyesus saying that the matter "requires further investigation".[30][31][32] The U.S. government and 13 other countries and the EU issued statements on the same day, echoing Tedros's critique of the report for lacking transparency and data access in its formulation.[33][34] In a later press conference, the WHO director-general said it was "premature" for the WHO's report to rule out a potential link between a laboratory leak and called on China to provide 'raw data' and lab audits in a second phase of investigations.[28][35] On 12 October 2021, the WHO announced a new team to study the origins of the COVID-19 pandemic.[36] In June 2022, this team released an additional report advocating for more investigations in the various possible pathways of emergence, including the possibility of a lab leak.[37]

Earlier, on 22 July 2021, the Chinese government had held a press conference in which Zeng Yixin, Vice Health Minister of the National Health Commission (NHC), said that China would not participate in a second phase of the WHO's investigation, denouncing it as "shocking" and "arrogant".[38][39] In response to the WHO's June 2022 report, Chinese Foreign Ministry spokesperson Zhao Lijian called the lab leak theory "a lie concocted by anti-China forces for political purposes, which has nothing to do with science".[40]

Scientific background
Main article: Severe acute respiratory syndrome coronavirus 2 § Virology

COVID-19 is caused by infection with a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 appears to have originated in bats and to have spread to humans by zoonotic transfer.[23][26][41] Its exact evolutionary history, the identity and provenance of its most recent ancestors, and the place, time, and mechanism of transmission of the first human infection, remain unknown.[1][42] The biology and regional distribution of other coronaviruses in southeast Asia, including SARS-CoV, help scientists understand more about the origins of SARS-CoV-2.[43]

Taxonomically, SARS-CoV-2 is a virus of the species severe acute respiratory syndrome–related coronavirus (SARSr-CoV).[44] It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus.[4][13][14][15] Research is ongoing as to whether SARS-CoV-2 came directly from bats or indirectly through any intermediate hosts.[16][17] The virus shows little genetic diversity, indicating that the spillover event introducing SARS-CoV-2 to humans is likely to have occurred in late 2019.[19] Ultimately, the specific evolutionary history of SARS-CoV-2 in relation to other coronaviruses will be critical to understanding how, where and when the virus spilled over into a human population.[45]

Reservoir and origin
Transmission of SARS-CoV-1 and SARS‑CoV‑2 from mammals as biological carriers to humans

No natural reservoir for SARS-CoV-2 has been identified.[11] Prior to the emergence of SARS-CoV-2 as a pathogen infecting humans, there had been two previous zoonosis-based coronavirus epidemics, those caused by SARS-CoV-1 and MERS-CoV.[46]

The first known infections from SARS‑CoV‑2 were discovered in Wuhan, China.[13] The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event.[4][19][43] Because many of the early infectees were workers at the Huanan Seafood Market,[47][48] it has been suggested that the virus might have originated from the market.[4][49] However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.[19][50] A March 2021 WHO-convened report stated that human spillover via an intermediate animal host was the most likely explanation, with direct spillover from bats next most likely. Introduction through the food supply chain and the Huanan Seafood Market was considered another possible, but less likely, explanation.[1] An analysis in November 2021, however, said that the earliest-known case had been misidentified and that the preponderance of early cases linked to the Huanan Market argued for it being the source.[51]

For a virus recently acquired through a cross-species transmission, rapid evolution is expected.[52] The mutation rate estimated from early cases of SARS-CoV-2 was of 6.54×10−4 per site per year.[1] Coronaviruses in general have high genetic plasticity,[53] but SARS-CoV-2's viral evolution is slowed by the RNA proofreading capability of its replication machinery.[54] For comparison, the viral mutation rate in vivo of SARS-CoV-2 has been found to be lower than that of influenza.[55]

Research into the natural reservoir of the virus that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses, most originating in horseshoe bats. The closest match by far, published on Nature (journal) in February 2022, were viruses BANAL-52 (96.8% resemblance to SARS‑CoV‑2), BANAL-103 and BANAL-236, collected in three different species of bats in Feuang, Laos.[56][57][58] An earlier source published in February 2020 identified the virus RaTG13, collected in bats in Mojiang, Yunnan, China to be the closest to SARS‑CoV‑2, with 96.1% resemblance.[13][59] None of the above are its direct ancestor.[60]

Samples taken from Rhinolophus sinicus, a species of horseshoe bats, show an 80% resemblance to SARS‑CoV‑2.

Bats are considered the most likely natural reservoir of SARS‑CoV‑2.[1][61] Differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans may have been infected via an intermediate host;[49] although the source of introduction into humans remains unknown.[62][11]

Although the role of pangolins as an intermediate host was initially posited (a study published in July 2020 suggested that pangolins are an intermediate host of SARS‑CoV‑2-like coronaviruses[63][64]), subsequent studies have not substantiated their contribution to the spillover.[1] Evidence against this hypothesis includes the fact that pangolin virus samples are too distant to SARS-CoV-2: isolates obtained from pangolins seized in Guangdong were only 92% identical in sequence to the SARS‑CoV‑2 genome (matches above 90 percent may sound high, but in genomic terms it is a wide evolutionary gap[65]). In addition, despite similarities in a few critical amino acids,[66] pangolin virus samples exhibit poor binding to the human ACE2 receptor.[67] Available scientific evidence suggests that SARS-CoV-2 has a natural zoonotic origin.[68][69][70][71][72][73] Yet its origin, which remains unknown, has become debated within the context of global geopolitical tensions.[72][74] Early in the pandemic, conspiracy theories spread on social media claiming that the virus was a biological weapon developed by China,[75] amplified by echo chambers in the American far-right.[76] Other conspiracy theories promoted misinformation that the virus is not communicable or was created to profit from new vaccines.[77]

Some politicians and scientists have speculated that the virus may have accidentally leaked from the Wuhan Institute of Virology.[74][78][79] This has led to calls in the media for further investigations into the matter.[80][5] Many virologists who have studied coronaviruses consider the possibility very remote.[77][81][82][83] The WHO-convened Global Study of the Origins of SARS-CoV-2 from March 2021 stated that such an explanation is extremely unlikely.[79][84] In an interview on 12 August 2021, Peter Ben Embarek, the chief investigator of the WHO team, told a Danish TV documentary that the WHO team felt pressured from Chinese scientists to put "extremely unlikely" as their assessment.[85]

A 2021 study found possible links between climate change and transmission of COVID-19 by bats. The authors found that climate-driven changes in the distribution and richness of bat species harboring coronaviruses may have occurred leading to a concentration of such species in eastern Asian hotspots (southern China, Myanmar and Laos). Tell conditions favors transmission of viruses. In this area live pangolins that are sold among other in the Wuhan wet market and are suspected of being the intermediate host in the transmission of SARS-COV-2 who cause the pandemic.[86][87] The study was cited at 22 other studies in the National Library of Medicine of the USA. [88] Before World Health Day 2022, the World Health Organization mentioned on its site that: "There is growing evidence of a direct connection between environmental change and the emergence or transmission of COVID-19".[89]

Phylogenetics and taxonomy
Genomic information
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
NCBI genome ID86693
Genome size29,903 bases
Year of completion2020
Genome browser (UCSC)

SARS‑CoV‑2 belongs to the broad family of viruses known as coronaviruses.[90] It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment. Coronaviruses infect humans, other mammals, including livestock and companion animals, and avian species.[91] Human coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS, fatality rate ~34%). SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.[92]

Like the SARS-related coronavirus implicated in the 2003 SARS outbreak, SARS‑CoV‑2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B).[93][94] Coronaviruses undergo frequent recombination.[71] The mechanism of recombination in unsegmented RNA viruses such as SARS-CoV-2 is generally by copy-choice replication, in which gene material switches from one RNA template molecule to another during replication.[95] The SARS-CoV-2 RNA sequence is approximately 30,000 bases in length,[96] relatively long for a coronavirus—which in turn carry the largest genomes among all RNA families.[97] Its genome consists nearly entirely of protein-coding sequences, a trait shared with other coronaviruses.[71]

Transmission electron micrograph of SARS‑CoV‑2 virions (red) isolated from a patient during the COVID-19 pandemic

A distinguishing feature of SARS‑CoV‑2 is its incorporation of a polybasic site cleaved by furin,[66][98] which appears to be an important element enhancing its virulence.[99] In SARS-CoV-2 the recognition site is formed by the incorporated 12 codon nucleotide sequence CCT CGG CGG GCA which corresponds to the amino acid sequence P RR A.[100] This sequence is upstream of an arginine and serine which forms the S1/S2 cleavage site (P RR A R↓S) of the spike protein.[101] Although such sites are a common naturally-occurring feature of other viruses within the Subfamily Orthocoronavirinae,[100] it appears in few other viruses from the Beta-CoV genus,[102] and it is unique among members of its subgenus for such a site.[66] The furin cleavage site PRRAR↓ is identical to that of the feline coronavirus, an alphacoronavirus 1 strain.[103]

Viral genetic sequence data can provide critical information about whether viruses separated by time and space are likely to be epidemiologically linked.[104] With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS‑CoV‑2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions;[96][105] the number of genomes increased to 42 by 30 January 2020.[106] A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a common ancestor", implying that the first human infection occurred in November or December 2019.[106] Examination of the topology of the phylogenetic tree at the start of the pandemic also found high similarities between human isolates.[68] As of 21 August 2021, 3,422 SARS‑CoV‑2 genomes, belonging to 19 strains, sampled on all continents except Antarctica were publicly available.[107]

On 11 February 2020, the International Committee on Taxonomy of Viruses announced that according to existing rules that compute hierarchical relationships among coronaviruses based on five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus from the 2003 SARS outbreak were insufficient to make them separate viral species. Therefore, they identified 2019-nCoV as a virus of Severe acute respiratory syndrome–related coronavirus.[108]

Origin scenarios

The origin of SARS-CoV-2 has been the subject of debate.[109] There are multiple proposed explanations for how SARS-CoV-2 was introduced into, and evolved adaptations suited to, the human population. There is significant evidence and agreement that the most likely original viral reservoir for SARS-CoV-2 is horseshoe bats, with the closest known viral relative being RaTG13. The evolutionary distance between SARS-CoV-2 and RaTG13 is estimated to be about 50 years (between 38 and 72 years).[110][111] The earliest human cases of SARS-CoV-2 were identified in Wuhan, but the index case remains unknown. RaTG13 was sampled from bats in Yunnan,[1][112] located roughly 1,300 km (810 mi) away from Wuhan,[113] and there are relatively few bat coronaviruses from Hubei province.[69] Each origin hypothesis attempts to explain this gap in virus evolution and location a different way. These scenarios continue to be investigated to identify the definitive origin of the virus.

Direct zoonotic transmission in a natural setting

The most direct pathway of introduction is direct zoonotic transmission (also known as spillover) from the reservoir species to humans. Scientists consider this to be a highly likely origin of the SARS-CoV-2 virus in humans. Human contact with bats has increased as human population centers encroach on bat habitats, leading to increased opportunities for spillover. Bats are a significant reservoir species for a diverse range of coronaviruses, and humans have been found with antibodies for them suggesting that this form of direct infection by bats is common. However, in this scenario, the direct ancestor of SARS-CoV-2 remains undiscovered in bats.[1][114]

Intermediate host

In addition to direct spillover, another pathway, considered highly likely by scientists, is that of transmission through an intermediate host.[7][115] Specifically, this implies that a cross species transmission occurred prior to the human outbreak and that it had pathogenic results on the animal. This pathway has the potential to allow for greater adaptation to human transmission via animals with more similar protein shapes to humans, though this is not required for the scenario to occur. The evolutionary separation from bat viruses is explained in this case by the virus' presence in an unknown species with less viral surveillance than bats.[116] The virus' ability to easily infect and adapt to additional species (including mink) provides evidence that such a route of transmission is possible.[1][115]

Cold/food chain

Another proposed introduction to humans is through fresh or frozen food products, referred to as the cold/food chain.[117] Scientists do not consider this to be a likely origin of SARS-CoV-2 in humans.[118] This scenario's source animal could be either a direct or intermediary species as described above. Many investigations centered around the Huanan Seafood Wholesale Market in Wuhan, which had an early cluster of cases. While there have been food-borne outbreaks of human viruses in the past, and evidence of re-introduction of SARS-CoV-2 into China through imported frozen foods, investigations found no conclusive evidence of viral contamination in products at the Huanan Market.[1][119]

Laboratory incident
Further information: COVID-19 lab leak theory

A final scenario, assessed to be unlikely by most experts,[23][24][25] but supported by a minority of experts,[120] is known as the lab leak hypothesis.[24] The theory considers that the possibility that the virus was introduced to humans due to an intentional or unintentional laboratory escape. This scenario would have involved laboratory staff becoming infected from contact with live bats (wild or captive), from contact with biological samples, or from contact with viruses being grown in vitro.[1][121] The Wuhan Institute of Virology (WIV) has performed research into bat coronaviruses since 2005, and identified the RaTG13 virus in 2013, which is the closest known relative of SARS-CoV-2.[24] WIV research interests have included investigations into the source of the 2002–2004 SARS outbreak and 2012 MERS outbreak, in collaboration with US researchers.[122][123] The proximity of the laboratory to the Huanan seafood market has led some to speculate there may be a link between the two,[124][125] and politicians, media personalities, and some scientists have called for further investigations into the matter.[126][127] Experts have ruled out intentional manipulation of the virus (i.e. biological engineering) as a plausible origin,[1][72][128][129][130] due to a lack of supporting evidence,[4][72][131] and growing evidence in favor of a natural origin.[132][133][134][135]

New York-based, National Institutes of Health–funded EcoHealth Alliance has been the subject of controversy and increased scrutiny due to its ties to the Wuhan Institute of Virology.[136][137][138][139] Under political pressure, the National Institutes of Health (NIH) withdrew funding to EcoHealth Alliance in July 2020.[140]

A WHO-convened study published in March 2021 considered the possibility of a collected natural virus inadvertently infecting laboratory staff, assessing it to be "extremely unlikely".[1][121] On 15 July 2021 WHO director-general Tedros Adhanom stated in a speech that there had been a "premature push" to discredit the idea of a lab leak.[141] Later on in the same speech, he expanded, "I was a lab technician, an immunologist, and worked in the lab. And lab accidents happen."[142] The WHO has planned a second phase of investigation that will include "audits of relevant laboratories and research institutions".[143] However, China has rejected this plan stating "it is impossible for us to accept such an origin-tracing plan".[144]

An even less likely lab-leak theory has been proposed by some in the Chinese government who have claimed that the virus came from a U.S. military laboratory.[145] Chinese government demands to investigate the U.S. lab at Fort Detrick have been said to be intended to deflect attention from Wuhan.[146]

Investigations

Chinese government

The first investigation conducted in China was by the Wuhan Municipal Health Commission, responding to hospitals reporting cases of pneumonia of unknown etiology, resulting in the closure of the Huanan Seafood Wholesale Market on 1 January 2020 for sanitation and disinfection.[147] The market was originally suspected of being the source of the virus; however, the Chinese government and the WHO determined later that it was not.[26][148][149]

In April 2020, China imposed restrictions on publishing academic research on the novel coronavirus. Investigations into the origin of the virus would receive extra scrutiny and must be approved by Central Government officials.[150][151] The restrictions do not ban research or publication, including with non-Chinese researchers; Ian Lipkin, a US scientist, has been working with a team of Chinese researchers under the auspices of the Chinese Center for Disease Control and Prevention, a Chinese government agency, to investigate the origin of the virus. Lipkin has long-standing relationships with Chinese officials, including premier Li Keqiang, because of his contributions to rapid testing for SARS in 2003.[152]

Trump administration

On 6 February 2020, the director of the White House's Office of Science and Technology Policy requested the National Academies of Sciences, Engineering, and Medicine to convene a meeting of "experts, world class geneticists, coronavirus experts, and evolutionary biologists", to "assess what data, information and samples are needed to address the unknowns, in order to understand the evolutionary origins of COVID-19 and more effectively respond to both the outbreak and any resulting information".[153][154]

In April 2020, it was reported that the US intelligence community was investigating whether the virus came from an accidental leak from a Chinese lab. The hypothesis was one of several possibilities being pursued by the investigators. US Secretary of Defense Mark Esper said the results of the investigation were "inconclusive".[155][156] By the end of April 2020, the Office of the Director of National Intelligence said the US intelligence community believed the coronavirus was not man-made or genetically modified.[157][158]

US officials criticised the "terms of reference" allowing Chinese scientists to do the first phase of preliminary research.[21] On 15 January 2021, US Secretary of State Mike Pompeo said that to assist the WHO investigative team's work and ensure a transparent, thorough investigation of COVID-19's origin, the US was sharing new information and urging the WHO to press the Chinese government to address three specific issues, including the illnesses of several researchers inside the WIV in autumn 2019 "with symptoms consistent with both COVID-19 and common seasonal illnesses", the WIV's research on "RaTG13" and "gain of function", and the WIV's links to the People's Liberation Army.[159][160] On 18 January, the US called on China to allow the WHO's expert team to interview "care givers, former patients and lab workers" in the city of Wuhan, drawing a rebuke from the Chinese government. Australia also called for the WHO team to have access to "relevant data, information and key locations".[161]

A classified report from May 2020 by the Lawrence Livermore National Laboratory, a US government national laboratory, concluded that the hypothesis that the virus leaked from the WIV "is plausible and deserves further investigation", although the report also notes that the virus could have developed naturally, echoing the consensus of the American intelligence community, and provides no "smoking gun" towards either hypothesis.[162][163]

Biden administration

On 13 February 2021, the White House said it had "deep concerns" about both the way the WHO's findings were communicated and the process used to reach them. Mirroring concerns raised by the Trump administration, National Security Adviser Jake Sullivan stated that it was essential that the WHO-convened report be independent and "free from alteration by the Chinese government".[164] On 14 April 2021, the Director of National Intelligence Avril Haines, along with other Biden administration officials, said that they had not ruled out the possibility of a laboratory accident as the origin of the COVID-19 virus.[165]

On 26 May 2021, President Joe Biden directed the U.S. intelligence community to produce a report within 90 days on whether the COVID-19 virus originated from a human contact with an infected animal or from an accidental lab leak,[166] stating his national security staff said there is insufficient evidence to determine either hypothesis to be more likely.[167] On 26 August 2021, the Office of the Director of National Intelligence released an unclassified summary of their findings,[168] with the main point being that the report remained inconclusive as to the origin of the virus, with intelligence agencies divided on the question.[169] The report also concluded that the virus was most likely not genetically engineered, and that China had no foreknowledge of the virus prior to the outbreak. The report concluded that a final determination of the origin was unlikely without cooperation from the Chinese government, saying their prior lack of transparency "reflect[ed] in part China's government's own uncertainty about where an investigation could lead, as well as its frustration that the international community is using the issue to exert political pressure on China."[170] Chinese foreign ministry spokesman Wang Wenbin said that the US intelligence report was "unscientific and has no credibility".[171]

On 23 May 2021, The Wall Street Journal reported that a previously undisclosed US intelligence report stated that three researchers from the Wuhan Institute of Virology became ill enough in November 2019 to seek hospital care. The report did not specify what the illness was. Officials familiar with the intelligence differed as to the strength to which it corroborates the hypothesis that the virus responsible for COVID-19 was leaked from the WIV. The WSJ report notes that it is not unusual for people in China to go to the hospital with uncomplicated influenza or common cold symptoms.[172]

Yuan Zhiming, director of the WIV's Wuhan National Biosafety Laboratory, responded in the Global Times, a Chinese state media outlet, that the "claims are groundless".[173][174] Marion Koopmans, a member of the WHO study team, described the number of flu-like illnesses at the WIV in 2019 as "completely normal".[175] Workers at the WIV must provide yearly serum samples.[1][175] WIV virologist Shi Zhengli said in 2020 that, based on an evaluation of those serum samples, all staff tested negative for COVID-19 antibodies.[172]

The resurgence of the theory of a laboratory accident was fueled in part by the publication, in May 2021, of early emails between Anthony Fauci and scientists discussing the issue, before deliberate manipulation was ruled out as of March 2020.[176]

On 14 July 2021, the House Committee on Science, Space and Technology held the first congressional hearing on the origins of the virus. Bill Foster, an Illinois Democrat who chaired the hearing, said the Chinese government's lack of transparency is not in itself evidence of a lab leak and cautioned that answers may not be known even after the administration produces its intelligence report.[177] Expert witnesses Stanley Perlman and David Relman presented to the congressman different proposed explanations for the origins of the virus and how to conduct further investigations.[178]

On 16 July 2021, CNN reported that Biden administration officials considered the lab leak theory "as credible" as the natural origins theory.[179] In October 2022, an interim report of a Republican member of a US Senate committee concluded that a lab origin was most likely, but offered "little new evidence", according to The New York Times.[180]

World Health Organization

The World Health Organization has declared that finding where SARS-CoV-2 came from is a priority and that it is "essential for understanding how the pandemic started."[181] In May 2020, the World Health Assembly, which governs the World Health Organization (WHO), passed a motion calling for a "comprehensive, independent and impartial" study into the COVID-19 pandemic. A record 137 countries, including China, co-sponsored the motion, giving overwhelming international endorsement to the study.[182] In mid 2020, the World Health Organization (WHO) began negotiations with the government of China on conducting an official study into the origins of COVID-19.

In November 2020, the WHO published a two-phase study plan. The purpose of the first phase was to better understand how the virus "might have started circulating in Wuhan", and a second phase involves longer-term studies based on the findings of the first phase.[1][183] WHO director-general Tedros Adhanom said "We need to know the origin of this virus because it can help us to prevent future outbreaks," adding, "There is nothing to hide. We want to know the origin, and that's it." He also urged countries not to politicise the origin tracing process, saying that would only create barriers to learning the truth.[184]

Phase 1

For the first phase, the WHO formed a team of ten researchers with expertise in virology, public health and animals to conduct a thorough study.[185] One of the team's tasks was to retrospectively ascertain what wildlife was being sold in local wet markets in Wuhan.[186] The WHO's phase one team arrived and quarantined in Wuhan, Hubei, China in January 2021.[161][187]

Members of the team included Thea Fisher, John Watson, Marion Koopmans, Dominic Dwyer, Vladimir Dedkov, Hung Nguyen-Viet, Fabian Leendertz, Peter Daszak, Farag El Moubasher, and Ken Maeda. The team also included five WHO experts led by Peter Ben Embarek, two Food and Agriculture Organization representatives, and two representatives from the World Organisation for Animal Health.[1]

The inclusion of Peter Daszak in the team stirred controversy. Daszak is the head of EcoHealth Alliance, a nonprofit that studies spillover events, and has been a longtime collaborator of over 15 years with Shi Zhengli, Wuhan Institute of Virology's director of the Center for Emerging Infectious Diseases.[188][189] While Daszak is highly knowledgeable about Chinese laboratories and the emergence of diseases in the area, his close connection with the WIV was seen by some as a conflict of interest in the WHO's study.[188][190] When a BBC News journalist asked about his relationship with the WIV, Daszak said, "We file our papers, it's all there for everyone to see."[191]

The team was denied access to raw data, including the list of early patients, swabs, and blood samples.[192] It was allowed only a few hours of supervised access to the Wuhan Institute of Virology.[193]

Findings

In February 2021, after conducting part of their study, the WHO stated that the likely origin of COVID-19 was a zoonotic event from a virus circulating in bats, likely through another animal carrier, and that the time of transmission to humans was likely towards the end of 2019.[26]

The Chinese and the international experts who jointly carried out the WHO-convened study consider it "extremely unlikely" that COVID-19 leaked from a lab.[26][194][195][196] No evidence of a lab leak from the Wuhan Institute of Virology was found by the WHO team, with team leader Peter Ben Embarek stating that it was "very unlikely" due to the safety protocols in place.[26] During a 60 Minutes interview with Lesley Stahl, Peter Daszak, another member of the WHO team, described the investigation process to be a series of questions and answers between the WHO team and the Wuhan lab staff. Stahl made the comment that the team was "just taking their word for it", to which Daszak replied, "Well, what else can we do? There's a limit to what you can do and we went right up to that limit. We asked them tough questions. They weren't vetted in advance. And the answers they gave, we found to be believable—correct and convincing."[197]

The investigation also stated that transfer from animals to humans was unlikely to have occurred at the Huanan Seafood Market, since infections without a known epidemiological link were confirmed before the outbreak around the market.[26] In an announcement that surprised some foreign experts, the joint investigation concluded that early transmission via the cold chain of frozen products was "possible."[26]

In March 2021, the WHO published a written report with the results of the study.[198] The joint team stated that there are four scenarios for introduction:[119]

  • direct zoonotic transmission to humans (spillover), assessed as "possible to likely"
  • introduction through an intermediate host followed by a spillover, assessed as "likely to very likely"
  • introduction through the (cold) food chain, assessed as "possible"
  • introduction through a laboratory incident, assessed as "extremely unlikely"

The report mentions that direct zoonotic transmission to humans has a precedent, as most current human coronaviruses originated in animals. Zoonotic transmission is also supported by the fact that RaTG13 binds to hACE2, although the fit is not optimal.[1][199]

The investigative team noted the requirement for further studies, noting that these would "potentially increase knowledge and understanding globally."[200][1]: 9 

Reactions

WHO director-general Tedros Adhanom, who was not directly involved with the investigation, said he was ready to dispatch additional missions involving specialist experts and that further research was required. He said in a statement, "Some explanations may be more probable than others, but for now all possibilities remain on the table."[201] He also said, "We have not yet found the source of the virus, and we must continue to follow the science and leave no stone unturned as we do." Tedros called on China to provide "more timely and comprehensive data sharing" as part of future investigations.[202]

News outlets noted that, though it was unrealistic to expect quick and huge results from the report, it "offered few clear-cut conclusions regarding the start of the pandemic", "failed to audit the Chinese official position at some parts of the report", and was "biased according to critics".[203][204][205][206] Other scientists praised how the report details the pathways that can shed light on the origin, if explored later.[207]

After the publication of the report, politicians, talk show hosts, journalists, and some scientists advanced unsupported claims that SARS-CoV-2 may have come from the WIV.[208] In the United States, calls to investigate a laboratory leak reached "fever pitch", fueling aggressive rhetoric resulting in antipathy towards people of Asian ancestry,[208][209] and the bullying of scientists.[210][211][212] The European Union, United States, and 13 other countries criticised the WHO-convened study, calling for transparency from China and access to the raw data and original samples.[213] Chinese officials described these criticisms as an attempt to politicise the study.[214] Scientists involved in the WHO report, including Liang Wannian, John Watson, and Peter Daszak, objected to the criticism, and said that the report was an example of the collaboration and dialogue required to successfully continue investigations into the matter.[215]

In a letter published in Science, a number of scientists, including Ralph Baric, argued that the accidental laboratory leak hypothesis had not been sufficiently investigated and remained possible, calling for greater clarity and additional data.[78][5] Their letter was criticized by some virologists and public health experts, who said that a "hostile" and "divisive" focus on the WIV was unsupported by evidence, and would cause Chinese scientists and authorities to share less, rather than more data.[208]

Phase 2
See also: Scientific Advisory Group for Origins of Novel Pathogens

On 27 May 2021, Danish epidemiologist Tina Fischer spoke on the This Week in Virology podcast, advocating for a second phase of the study to audit blood samples for COVID-19 antibodies in China.[216][217] WHO-convened study team member Marion Koopmans, on that same broadcast, advocated for WHO member states to make a decision on the second phase of the study, though she also cautioned that an investigatory audit of the laboratory itself may be inconclusive.[216][217] In early July 2021, WHO emergency chief Michael Ryan said the final details of phase 2 were being worked out in negotiations between WHO and its member states, as the WHO works "by persuasion" and cannot compel any member state (including China) to cooperate.[218]

In July 2021 China rejected WHO requests for greater transparency, cooperation, and access to data as part of Phase 2. On 16 July 2021, Foreign Ministry spokesperson Zhao Lijian declared that China's position was that future investigations should be conducted elsewhere and should focus on cold chain transmission and the US military's labs.[219] On 22 July 2021, the Chinese government held a press conference in which Zeng Yixin, Vice Health Minister of the National Health Commission (NHC), said that China would not participate in a second phase of the WHO's investigation, denouncing it as "shocking" and "arrogant".[38] He elaborated "In some aspects, the WHO's plan for next phase of investigation of the coronavirus origin doesn't respect common sense, and it's against science. It's impossible for us to accept such a plan."[39]

On 9 June 2022, the SAGO group, in development of its function of advisor to the WHO, published its first preliminary report. This report summarised existing findings and recommended that further studies be undertaken into possibly pathways of emergence.[37]

The Lancet COVID-19 Commission task force

In November 2020, an international task force led by Peter Daszak, president of EcoHealth Alliance, was formed as part of The Lancet COVID-19 Commission, backed by the medical journal The Lancet.[220] Daszak stated that the task force was formed to "conduct a thorough and rigorous investigation into the origins and early spread of SARS-CoV-2". The task force has twelve members with backgrounds in One Health, outbreak investigation, virology, lab biosecurity and disease ecology.[221][222] The task force plans to analyse scientific findings and does not plan to visit China.[220] In June 2021, The Lancet announced that Daszak had recused himself from the commission.[223] On 25 September 2021, the task force work was folded after procedural concerns and a need to broaden its scope to examine transparency and government regulation of risky laboratory research.[224]

In September 2022 the Lancet group published a wide-ranging report on the pandemic, including commentary on the virus origin overseen by the group's chairman, economist Jeffrey Sachs.[225] The report suggested that the virus may have originated from an American laboratory, a notion long-promoted by Sachs, including on the podcast of conspiracy theorist Robert F. Kennedy Jr..[226][227] Reacting to this, virologist Angela Rasmussen commented that this may have been "one of The Lancet's most shameful moments regarding its role as a steward and leader in communicating crucial findings about science and medicine".[227] Virologist David Robertson said the invocation of US laboratory involvement was "wild speculation" and that "it's really disappointing to see such a potentially influential report contributing to further misinformation on such an important topic".[227]

Independent investigations

In June 2021, the NIH announced that a set of sequence data had been removed from the Sequence Read Archive (SRA) in June 2020. The removal was performed according to standard practice at the request of the investigators who owned the rights to the sequences, with the investigators' rationale that the sequences would be submitted to another database.[228][229] The investigators subsequently published a paper in an academic journal the same month they were removed from the NIH database which described the sequences in detail and discussed their evolutionary relationship to other sequences, but did not include the raw data.[230] Virologist David Robertson said that it was difficult to conclude it was a cover-up rather than the more likely explanation: a mundane deletion of data without malfeasance.[231][232] The missing genetic sequence data was restored in a correction published 29 July 2021 after it was stated to be a copy-edit error.[233][234]

International calls for investigations

In April 2020, Australian foreign minister Marise Payne and Australian prime minister Scott Morrison called for an independent international inquiry into the origins of the coronavirus pandemic.[235][236] A few days later, German chancellor Angela Merkel also pressed China for transparency about the origin of the coronavirus, following similar concerns raised by the French president Emmanuel Macron.[237] The UK also expressed support for an investigation, although both France and UK said the priority at the time was to first fight the virus.[238][239] Some public health experts have also called for an independent examination of COVID-19's origins, "arguing WHO does not have the political clout to conduct such a forensic analysis".[240]

In May 2021, Prime Minister Justin Trudeau told reporters Canada would "support the call by the United States and others to better understand the origins of COVID-19."[241][242] In June 2021, at the G7 summit in Cornwall, the attending leaders issued a joint statement calling for a new investigation, citing China's refusal to cooperate with certain aspects of the original WHO-convened study.[243] This resistance to international pressure was one of the key findings of a Wall Street Journal investigation into the pandemic origin.[244]

The divisive nature of the debate has led scientists to call for less political pressure on the topic.[176] Public health analysts have remarked that the debate over the origins of SARS-CoV-2 is fueling unnecessary confrontation, resulting in bullying and harassment of scientists,[245] and is deepening existing geopolitical tensions and hindering collaboration at a time where such mutual cooperation is required, both to deal with the current pandemic and in preparation for future such outbreaks.[74][246] This comes in the face of scientists having predicted such events for decades: according to Katie Woolaston, researcher at the Queensland University of Technology, "The environmental drivers of pandemics are not being widely discussed". The debate comes at a moment of difficult global relations with Chinese authorities. Researchers have noted that the politicisation of the debate is making the process more difficult, and that words are often twisted to become "fodder for conspiracy theories."[247][248]

A letter published in The Lancet in July 2021 remarked that the atmosphere of speculation surrounding the issue was of no help in making an objective assessment of the situation.[127] In response to this letter, in a communication published in the same journal, a small group of researchers opposed the idea that scientists should promote unity and called for openness to alternative hypotheses.[249] Despite the unlikelihood of the event, and although definitive answers are likely to take years of research, biosecurity experts have called for a review of global biosecurity policies, citing known gaps in international standards for biosafety.[74][247] The situation has also reignited a debate over gain-of-function research, although the intense political rhetoric surrounding the issue has threatened to sideline serious inquiry over policy in this domain.[250]

See also

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