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Investigations into the origin of COVID-19

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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. The scientific consensus is that it is a zoonotic virus that arose from bats in a natural setting.[1][2][3]

SARS-CoV-2 is a virus of the species severe acute respiratory syndrome–related coronavirus (SARSr-CoV).[4] It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus.[5][6][7][8] Research is ongoing as to whether SARS-CoV-2 came directly from bats or indirectly through any intermediate hosts.[9][10] 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.[11][12]

Health authorities and scientists internationally state that efforts to trace the specific geographic and taxonomic origins of SARS-CoV-2 could take years, and the results could be inconclusive.[13] A number of conspiracy theories have been promoted about the origins of the virus.[14][15][16] Echoing the views of scientists internationally, a World Health Organization (WHO) mission said that a laboratory leak origin for the virus was "extremely unlikely",[14] supporting what most experts already expected about the likely natural origins of the virus and its early transmission.[17] The WHO director-general Tedros Adhanom Ghebreyesus said he was ready to deploy additional missions for further investigation.[18]

Scientific consensus on origins

Main article: Coronavirus disease 2019 § History

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 was spread to humans by zoonotic transfer.[17][19][20] 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.[21][22] 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.[23]

Taxonomically, SARS-CoV-2 is a virus of the species severe acute respiratory syndrome–related coronavirus (SARSr-CoV).[4] It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus.[5][6][7][8] Research is ongoing as to whether SARS-CoV-2 came directly from bats or indirectly through any intermediate hosts.[9][10] 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.[12] 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.[24]

Reservoir and zoonotic origin

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

The first known infections from SARS‑CoV‑2 were discovered in Wuhan, China.[5] The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event.[12][23][8] Because many of the early infectees were workers at the Huanan Seafood Market,[25][26] it has been suggested that the virus might have originated from the market.[8][27] However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.[12][28] A March 2021 WHO report on a joint WHO-China study 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.[29]

A phylogenetic network analysis of 160 early coronavirus genomes sampled from December 2019 to February 2020 showed that the virus type most closely related to the bat coronavirus was most abundant in Guangdong, China, and designated type "A". The predominant type among samples from Wuhan, "B", is more distantly related to the bat coronavirus than the ancestral type "A".[30][31]

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 the Rhinolophus genus of horseshoe bats. Phylogenetic analysis indicates that samples taken from Rhinolophus sinicus show a resemblance of 80% to SARS‑CoV‑2.[7][32][33] Phylogenetic analysis also indicates that a virus from Rhinolophus affinis, collected in Yunnan province and designated RaTG13, has a 96% resemblance to SARS‑CoV‑2.[5][34] The RaTG13 virus sequence is the closest known sequence to SARS-CoV-2.[29]

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,[35][36] but differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans were infected via an intermediate host.[27]

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[37][38]), subsequent studies have not substantiated their contribution to the spillover.[29] 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. In addition, despite similarities in a few critical amino acids,[39] pangolin virus samples exhibit poor binding to the human ACE2 receptor.[40]

All available evidence suggests that SARS‑CoV‑2 has a natural animal origin and is not genetically engineered.[41] Nevertheless, early in the pandemic, conspiracy theories spread on social media claiming that the virus was bio-engineered by China at the Wuhan Institute of Virology.[42] While some, including former CDC director Robert R. Redfield, have claimed that the virus may have been studied by and escaped from the Institute,[43] virologists who have studied coronaviruses consider the possibility very remote, and the March 2021 WHO report on the joint WHO-China study stated that such an explanation is "extremely unlikely".[43][29]


Phylogenetics and taxonomy

Genomic information
SARS-CoV-2 genome.svg
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.[44] It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment. Other 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%). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.[45]

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).[46][47] Coronaviruses also undergo frequent recombination.[48] Its RNA sequence is approximately 30,000 bases in length,[49] relatively long for a coronavirus. SARS‑CoV‑2 is unique among known betacoronaviruses in its incorporation of a polybasic site cleaved by furin,[50] a characteristic known to increase pathogenicity and transmissibility in other viruses.[8][51][52]

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;[49][53] the number of genomes increased to 42 by 30 January 2020.[54] 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.[54] As of 7 May 2020, 4,690 SARS‑CoV‑2 genomes sampled on six continents were publicly available.[11][clarification needed]

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.[55]

Further investigations by scientific bodies

World Health Organization investigations

In mid 2020, the World Health Organization (WHO) began negotiations with the government of China on conducting an investigation 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.[56]

For the first phase, the WHO formed a team of ten researchers with expertise in virology, public health and animals to conduct investigations.[57] The WHO's phase one investigation team arrived and quarantined in Wuhan, Hubei, China in January 2021.[58][59]

Members of the investigative 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.[60] 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.[61][62] While Daszak is highly knowledgeable about Chinese laboratories and the emergence of diseases in the area, his close connection with the WIV was seen as a conflict of interest[by whom?] in the WHO's investigation.[61][63] 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."[64]

In February 2021, after conducting part of their investigation, the WHO stated that the likely origin of COVID-19 was bats, and that the likely time of transmission to humans was towards the end of 2019. While the WHO investigation's objectives were not about fully determining the origins of the virus, which may take years, it confirmed the existing consensus among experts.[17] The most likely origin remains bats, likely through another animal carrier.[17]

The Chinese and the international experts who carried out the joint investigation stated that it was "extremely unlikely" that COVID-19 leaked from a lab.[17][65][66][67] No evidence of a lab leak from the Wuhan Institute of Virology was found, and WHO team leader Peter Ben Embarek stated that it was "very unlikely" due to the safety protocols in place.[17]

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.[17] Early transmission is also unlikely to have occurred via the "cold chain" of frozen products.[17]

In March 2021, the WHO published the written report with the results of the joint study.[68] The joint team stated that there are four scenarios for introduction:

  • 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.

An argument in favor of direct zoonotic transmission to humans is the precedent that most of the current human coronaviruses have originated in animals. This path is also supported by the fact that RaTG13 does bind to hACE2, although the fit is not optimal.[68]

The investigative team noted the requirement for further studies, noting that these would "potentially increase knowledge and understanding globally".[68] The WHO director-general Tedros Adhanom Ghebreyesus said he was ready to dispatch additional missions involving specialist experts. He said in a statement, "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."[18]

The Lancet COVID-19 Commission task force

On 23 November 2020, an international task force led by Peter Daszak, president of EcoHealth Alliance, was formed as part of The Lancet COVID-19 Commission, chaired by economist Jeffrey Sachs of Columbia University. The task forced is backed by the medical journal The Lancet.[69] 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.[70] The task force plans to analyze scientific findings and does not plan to visit China.[69]

Investigations by governments

In May 2020, the World Health Assembly, which governs the World Health Organization (WHO), passed a motion calling for a "comprehensive, independent and impartial" investigation into the COVID-19 pandemic. A record 137 countries, including China, co-sponsored the motion, giving overwhelming international endorsement to the investigation.[71]

In November 2020, WHO director-general Tedros Adhanom Ghebreyesus 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 politicize the origin tracing process, saying that would only create barriers to learning the truth.[72]

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.[43] 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.[73][74][17]

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.[75][76] 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.[77]

The Chinese government has said that COVID-19 may have first been transmitted to Wuhan from abroad, via frozen food imports.[78][79] Scientists from the World Health Organization and other agencies have said there is no evidence for COVID-19 being transmitted through the food chain and that the risks are "negligible".[80][81][82]

United States government

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".[83][84]

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".[85][86] 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.[87][88]

US officials[who?] previously denounced the WHO investigation as a "Potemkin exercise" and criticised the "terms of reference" allowing Chinese scientists to do the first phase of preliminary research.[89][90] 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, the WIV's research on "RaTG13" and "gain of function", and the WIV's links to the Chinese military.[91] 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".[58]

Biden administration

On 13 February 2021, the White House said it has "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 it is essential that the report be independent and "free from alteration by the Chinese Government".[92] On 14 April 2021, the Director of National Intelligence Avril Haines, and other officials of the Biden Administration, said that they had not ruled out the possibility of a laboratory accident as the origin of the Covid-19 virus.[93]

International policitians' 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.[94][95] 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.[96] Britain also expressed support for an investigation, although both France and Britain said the priority at the time was to first fight the virus.[97][98]

See also

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