rs79.vrx.palo-alto.ca.us
Origins of SARS-CoV-2

The Consequences of a Lab Escape of a Potential Pandemic Pathogen

Whatever number we are gambling with, it is clearly far too high a risk to human lives. This Asian bird flu virus research to develop strains transmissible via aerosols among mammals, and perhaps some other PPP research as well, should for the present be banned. We must emphasize that we have been considering only a very small subset of pathogen research. Most pathogen research should proceed unimpeded by unnecessary regulations.


Engineered bat virus stirs debate over risky research

Lab-made coronavirus related to SARS can infect human cells.

Although almost all coronaviruses isolated from bats have not been able to bind to the key human receptor, SHC014 is not the first that can do so. In 2013, researchers reported this ability for the first time in a different coronavirus isolated from the same bat population


Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond

Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed the species barriers to infect humans. The mechanism of viral interspecies transmission is an important scientific question to be addressed. These coronaviruses contain a surface-located spike (S) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. In addition, the S protein needs to be cleaved by host proteases before executing fusion, making these proteases a second determinant of coronavirus interspecies infection. Here, we summarize the progress made in the past decade in understanding the cross-species transmission of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its receptor-binding characteristics, and the cleavage process involved in priming.


A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations1. Using the SARS-CoV reverse genetics system2, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.


The next SARS?

Human-infecting coronaviruses (CoVs), such as SARS-CoV and MERS-CoV, are thought to emerge from circulating bat CoVs. To test the emergence potential of SARS-like CoVs currently present in bats, Menachery et al. selected the bat CoV SHC014 (which metagenomics studies identified as a close relative to the epidemic SARS strains) and cloned its spike protein (which mediates viral attachment to host cells) into a mouse-adapted SARS-CoV backbone. The chimeric virus could replicate inside human cell lines and was capable of replicating in mouse lungs. Importantly, currently available therapeutics (monoclonal antibodies and vaccines) failed to protect the mice from viral infection. Finally, the authors synthesized a full-length SHC014 CoV, which was capable of replicating in human cells. These data suggest that CoVs currently circulating in bats have the potential for human emergence.


Novel Coronavirus found in bats in 2018 in Myanmar


From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen"

An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.

In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done.

From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats.


https://www.nature.com/articles/s41591-020-0820-9

The proximal origin of SARS-CoV-2

SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.


Coronavirus origins: genome analysis suggests two viruses may have combined

In addition, these genomic comparisons suggest that the SARS-Cov-2 virus is the result of a recombination between two different viruses, one close to RaTG13 and the other closer to the pangolin virus. In other words, it is a chimera between two pre-existing viruses.


By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 27 (66%) of 41 patients had been exposed to Huanan seafood market.


The Case Is Building That COVID-19 Had a Lab Origin

But one other troubling possibility must be dispensed with. It follows from the fact that the epicentre city, Wuhan (pop. 11 million), happens to be the global epicentre of bat coronavirus research (e.g. Hu et al., 2017).


Did this virus come from a lab? Maybe not — but it exposes the threat of a biowarfare arms race

Dangerous pathogens are captured in the wild and made deadlier in government biowarfare labs. Did that happen here?

This reporter raised questions about the subject at a news conference with a Center for Disease Control (CDC) representative at the now-shuttered National Press Club on Feb. 11. I asked if it was a "complete coincidence" that the pandemic had started in Wuhan, the only place in China with a declared biosafety level 4 (BSL4) laboratory. BSL4 laboratories have the most stringent safety mechanisms, but handle the most deadly pathogens. As I mentioned, it was odd that the ostensible origin of the novel coronavirus was bat caves in Yunnan province — more than 1,000 miles from Wuhan. I noted that "gain-of-function" lab work can results in more deadly pathogens, and that major labs, including some in the U.S., have had accidental releases.

More from his blog


Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2

We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome–related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.


The divergence between SARS-CoV-2 and RaTG13 might be overestimated due to the extensive RNA modification

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. There is urgent need to understand the phylogeny, divergence and origin of SARS-CoV-2. Materials & methods: A recent study claimed that there was 17% divergence between SARS-CoV-2 and RaTG13 (a SARS-related coronaviruses) on synonymous sites by using sequence alignment. We re-analyzed the sequences of the two coronaviruses with the same methodology. Results: We found that 87% of the synonymous substitutions between the two coronaviruses could be potentially explained by the RNA modification system in hosts, with 65% contributed by deamination on cytidines (C-T mismatches) and 22% contributed by deamination on adenosines (A-G mismatches). Conclusion: Our results demonstrate that the divergence between SARS-CoV-2 and RaTG13 has been overestimated.


No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2

Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV (RaTG13) was recently reported, which shared ∼96% homology with the SARS-CoV-2 [4]. However, as we know, the human SARS-CoV and intermediate host palm civet SARS-like CoV shared 99.8% homology, with a total of 202 single-nucleotide (nt) variations (SNVs) identified across the genome [6]. Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV [4], which are distributed throughout the genome in a naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species (bats) are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published (https://www.nature.com/articles/d41586-020-00364-2).

Another claim in Chinese social media points to a Nature Medicine paper published in 2015 [7], which reports the construction of a chimeric CoV with a bat CoV S gene (SHC014) in the backbone of a SARS CoV that has adapted to infect mice (MA15) and is capable of infecting human cells [8]. However, this claim lacks any scientific basis and must be discounted because of significant divergence in the genetic sequence of this construct with the new SARS-CoV-2 (>5,000 nucleotides).

The mouse-adapted SARS virus (MA15) [9] was generated by serial passage of an infectious wildtype SARS CoV clone in the respiratory tract of BALB/c mice. After 15 passages in mice, the SARS-CoV gained elevated replication and lung pathogenesis in aged mice (hence M15), due to six coding genetic mutations associated with mouse adaptation. It is likely that MA15 is highly attenuated to replicate in human cells or patients due to the mouse adaptation.

It was proposed that the S gene from bat-derived CoV, unlike that from human patients- or civets-derived viruses, was unable to use human ACE2 as a receptor for entry into human cells [10,11]. Civets were proposed to be an intermediate host of the bat-CoVs, capable of spreading SARS CoV to humans [6,12]. However, in 2013 several novel bat coronaviruses were isolated from Chinese horseshoe bats and the bat SARS-like or SL-CoV-WIV1 was able to use ACE2 from humans, civets and Chinese horseshoe bats for entry [8]. Combined with evolutionary evidence that the bat ACE2 gene has been positively selected at the same contact sites as the human ACE2 gene for interacting with SARS CoV [13], it was proposed that an intermediate host may not be necessary and that some bat SL-CoVs may be able to directly infect human hosts. To directly address this possibility, the exact S gene from bat coronavirus SL-SHC014 was synthesized and used to generate a chimeric virus in the mouse adapted MA15 SARS-CoV backbone. The resultant SL-SHC014-MA15 virus could indeed efficiently use human ACE2 and replicate in primary human airway cells to similar titres as epidemic strains of SARS-CoV. While SL-SHC014-MA15 can replicate efficiently in young and aged mouse lungs, infection was attenuated, and less virus antigen was present in the airway epithelium as compared to SARS MA15, which causes lethal outcomes in aged mice [7].

Due to the elevated pathogenic activity of the SHC014-MA15 chimeric virus relative to MA15 chimeric virus with the original human SARS S gene in mice, such experiments with SL-SHC014-MA15 chimeric virus were later restricted as gain of function (GOF) studies under the US government-mandated pause policy (https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research). The current COVID-2019 epidemic has restarted the debate over the risks of constructing such viruses that could have pandemic potential, irrespective of the finding that these bat CoVs already exist in nature. Regardless, upon careful phylogenetic analyses by multiple international groups [5,14], the SARS-CoV-2 is undoubtedly distinct from SL-SHC014-MA15, with >6,000 nucleotide differences across the whole genome. Therefore, once again there is no credible evidence to support the claim that the SARS-CoV-2 is derived from the chimeric SL-SHC014-MA15 virus.


Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning 24,341–30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch.

The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.


Origin of coronavirus

This is a really odd paper. Fact or fiction? See also, This


New Evidence the US Did Bring COVID-19 to Wuhan During the Military Games

WUHAN OUTBREAK: CHINA DEMANDS AN HONEST ACCOUNTING

Chinese authorities are awaiting an explanation from US authorities.

The big question now is whether the transmission was planned, or accidental.

The American Military Games team trained at a location near Fort Detrick, the military’s viral lab closed down by the CDC in July for various deficiencies.

42 employees of the Oriental Hotel were diagnosed with COVID-19, becoming the first cluster in Wuhan. At the time only 7 people from the market had been thus diagnosed (and treated before the hotel staff). All 7 had contact with the 42 from the hotel. From this source, the virus spread to the rest of China.

Five of the US troops developed a fever on Oct. 25 and were taken to an infectious-diseases hospital for treatment.The 300-strong US contingent stayed 300 meters from the Huanan Seafood Market where China’s outbreak began (see map below) at the Wuhan Oriental Hotel.

It is now virtually certain that COVID-19 was brought to Wuhan by American troops taking part in the city’s World Military Games last Oct. 18-27.

A few days ago, Mike Pompeo phoned Yang Jiechi, Chinese State Councillor for Foreign Affairs. Pompeo’s counterpart is actually Foreign Minister Wang Yi and Yang is Wang’s boss, so Pompeo wanted to talk about something urgent and important.

Pompeo wanted the Chinese not to publicize what they had found.

Yang’s reply: “We await your solemn explanation, especially about Patient Zero.”


"Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2" - Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between PangolinCoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs


State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses

Two years before the novel coronavirus pandemic upended the world, U.S. Embassy officials visited a Chinese research facility in the city of Wuhan several times and sent two official warnings back to Washington about inadequate safety at the lab, which was conducting risky studies on coronaviruses from bats. The cables have fueled discussions inside the U.S. government about whether this or another Wuhan lab was the source of the virus — even though conclusive proof has yet to emerge.

In January 2018, the U.S. Embassy in Beijing took the unusual step of repeatedly sending U.S. science diplomats to the Wuhan Institute of Virology (WIV), which had in 2015 become China’s first laboratory to achieve the highest level of international bioresearch safety (known as BSL-4). WIV issued a news release in English about the last of these visits, which occurred on March 27, 2018. The U.S. delegation was led by Jamison Fouss, the consul general in Wuhan, and Rick Switzer, the embassy’s counselor of environment, science, technology and health. Last week, WIV erased that statement from its website, though it remains archived on the Internet.


"...between Oct. 7 and Oct. 24, no mobile phone data was recorded coming from part of the site thought to be the high-security National Biosafety Laboratory..."

NBC added that US and UK intelligence agencies are examining a privately compiled report suggesting that between Oct. 7 and Oct. 24, no mobile phone data was recorded coming from part of the site thought to be the high-security National Biosafety Laboratory. The site was previously a source of frequent mobile phone activity prior to Oct. 7, leading the report’s authors to speculate that a “hazardous event” might have taken place some time between Oct. 6 and Oct. 11. In the intelligence report, seen by NBC, mobile data also suggested that police roadblocks were put in place between Oct. 14 and Oct. 19. But there are doubts over the report’s veracity and the identity of its authors, with experts saying it may be based solely on commercially available mobile phone data, which would be limited in its scope. Ruaridh Arrow, head of NBC News London’s Verification Unit, also urged caution, saying the data “may be misleading.”


Claims arose "Huang Yanling", a Wuhan lab worked was “patient zero” but Huang left in 2015, was in good health and never had covid-19.

Prof Ebright said he has seen evidence that scientists at the Centre for Disease Control and the Institute of Virology studied the viruses with only “level 2” security — rather than the recommended level 4 – which “provides only minimal protection against infection of lab workers,” the report said.

He concluded that the evidence left “a basis to rule out [that coronavirus is] a lab construct, but no basis to rule out a lab accident.”

Intriguingly, when the wildlife market was closed in January, a report appeared in the Beijing News identifying Huang Yanling, a researcher at the Institute of Virology, as “patient zero” – the first person to be infected.

The claim was described as “fake information” by the institute, which said Huang left in 2015, was in good health and had not been diagnosed with Covid-19.


Most of us have heard that this virus "started" in a wildlife market in Wuhan. But the source of the virus - an animal with this pathogen in its body - was not found in the market.

"The initial cluster of infections was associated with the market - that is circumstantial evidence," explained Prof James Wood from the University of Cambridge.

"The infection could have come from somewhere else and just, by chance, clustered around people there. But given that it is an animal virus, the market association is highly suggestive."


It might have been the US army representatives to the Military World Games who brought the novel coronavirus to Wuhan in October 2019

Chinese netizens and experts urge the US authority to release health and infection information of the US military delegation which came to Wuhan for the Military World Games in October to end the conjecture about US military personnel bringing COVID-19 to China.

An American journalist claimed one US military athlete in the delegation could be patient zero of the deadly new disease.

George Webb, an investigative journalist in Washington, DC claimed in recent videos and tweets that he believes Maatje Benassi, an armed diplomatic driver and cyclist who was in Wuhan in October for the cycling competition in the Military World Games, could be patient zero of COVID-19 in Wuhan.

In a report by the US Department of Defense official website on October 25, Maatje Benassi has participated 50-mile cycling road race in Wuhan.

Webb also quoted a military lab, the Fort Detrick laboratory that handles high-level disease-causing organisms such as Ebola, in Fredrick, Maryland, which was shut down and moved in July due to unqualified facilities and management system.

His conclusions, although without strong evidence, triggered questions on Chinese social media as it came only days after a petition was submitted to the White House website on March 10 listing some coincidences in time between the Fort Detrick lab's closure and the COVID-19 outbreak.

Many Chinese netizens have urged the US to test Benassi for COVID-19 and release information on the US delegation.

Li Haidong, a professor of US studies at the China Foreign Affairs University in Beijing, told the Global Times on Tuesday that the US government needs to respond to the controversy and publish the relevant information regarding their health status and infection record to clear public doubts and help with the scientific study on the virus' origin.

US politicians have been contending the novel coronavirus is "Made in China," while global scientists, including those in the US, have not found strong evidence to prove the virus' origin.

Given this situation, it is important to trace any suspicious points, the US delegation to the Wuhan games in this scenario, and find out what really happened, Li said. Earlier in March, Zhao Lijian, an outspoken Chinese diplomat, raised a suspicion on his personal Twitter account that it might have been the US army representatives to the Military World Games who brought the novel coronavirus to Wuhan in October 2019, after a top US health official admitted detecting coronavirus infections on some deceased flu patients. Zhao urged the US to disclose further information, exercise transparency on coronavirus cases and provide an explanation to the public.


The Long History of Accidental Laboratory Releases of Potential Pandemic Pathogens Is Being Ignored In the COVID-19 Media Coverage

Many people are dismissing the possibility that the COVID-19 pandemic might have come from a lab. It is possible that they are unaware of the frequency of biohazards escaping from laboratories.


Telemetry data from the Wuhan BSL4 lab


The report — obtained by the London-based NBC News Verification Unit — says there was no cellphone activity in a high-security portion of the Wuhan Institute of Virology from Oct. 7 through Oct. 24, 2019, and that there may have been a "hazardous event" sometime between Oct. 6 and Oct. 11.


"...a new virus..."

HONG KONG — Chinese researchers say they have identified a new virus behind an illness that has infected dozens of people across Asia, setting off fears in a region that was struck by a deadly epidemic 17 years ago.

There is no evidence that the new virus is readily spread by humans, which would make it particularly dangerous, and it has not been tied to any deaths. But health officials in China and elsewhere are watching it carefully to ensure that the outbreak does not develop into something more severe.


Scientists in China sequenced the virus’s genome and made it available on Jan. 10, just a month after the Dec. 8 report of the first case of pneumonia from an unknown virus in Wuhan.

In contrast, after the SARS outbreak began in late 2002, it took scientists much longer to sequence that coronavirus. It peaked in February 2003 — and the complete genome of 29,727 nucleotides wasn’t sequenced until that April.


"... on January 20, Chinese President Xi Jinping made his first public statement on the outbreak..."

“From that perspective, it looks like China is reporting now,” Hoffman added, noting there’s no evidence, at this time, that they’re withholding information. “But you always need to be worried: When one source isn’t as forthcoming from the beginning, you never know later on.” And if this virus continues to move at a dizzying speed, the question of whether China mischaracterized what they knew about the virus will become even more urgent.

“It’s crucial to understand the earliest days” of an outbreak, said Georgetown’s Lucey. Not only does it help us understand how deadly and transmissible a virus is, “it gets at how there’s been such rapid spread of the virus — not just across Wuhan, but to every province in China except for Tibet.”


Emerging SARS-CoV-2 Variants

Multiple SARS-CoV-2 variants are circulating globally. Several new variants emerged in the fall of 2020, most notably:

o In the United Kingdom (UK), a new variant of SARS-CoV-2 (known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7) emerged with a large number of mutations. This variant has since been detected in numerous countries around the world, including the United States (US). In January 2021, scientists from UK reported evidence[1] that suggests the B.1.1.7 variant may be associated with an increased risk of death compared with other variants. More studies are needed to confirm this finding. This variant was reported in the US at the end of December 2020.

o In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged independently of B.1.1.7. This variant shares some mutations with B.1.1.7. Cases attributed to this variant have been detected in multiple countries outside of South Africa. This variant was reported in the US at the end of January 2021.

o In Brazil, a variant of SARS-CoV-2 (known as P.1) emerged that was first was identified in four travelers from Brazil, who were tested during routine screening at Haneda airport outside Tokyo, Japan. This variant has 17 unique mutations, including three in the receptor binding domain of the spike protein. This variant was detected in the US at the end of January 2021.




2014 Klotz: The Consequences of a Lab Escape of a Potential Pandemic Pathogen
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128296/


2015 Butler: Engineered bat virus stirs debate over risky research
https://www.nature.com/news/engineered-bat-virus-stirs-debate-over-risky-research-1.18787


2015-Lu: Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond
https://www.sciencedirect.com/science/article/pii/S0966842X15001316


2015 Menachary: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence
https://www.nature.com/articles/nm.3985


2015 nuns-alves: The next SARS?
https://www.nature.com/articles/nrmicro.2015.17


2018 Smithsonian: Novel Coronavirus found in bats in 2018 in Myanmar
https://www.smithsonianmag.com/science-nature/global-surveillance-program-identifies-never-seen-virus-myanmars-bats-180969598/


2020 Chan: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen"
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30154-9/fulltext


2020 Anderson: The proximal origin of SARS-CoV-2
https://www.nature.com/articles/s41591-020-0820-9


2020 Hassanin: Coronavirus origins: genome analysis suggests two viruses may have combined
https://theconversation.com/coronavirus-origins-genome-analysis-suggests-two-viruses-may-have-combined-134059


2020 Huang: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext


2020 Latham: The Case Is Building That COVID-19 Had a Lab Origin
https://www.independentsciencenews.org/health/the-case-is-building-that-covid-19-had-a-lab-origin/


2020 Husseini: Did this virus come from a lab? Maybe not — but it exposes the threat of a biowarfare arms race
https://www.salon.com/2020/04/24/did-this-virus-come-from-a-lab-maybe-not--but-it-exposes-the-threat-of-a-biowarfare-arms-race/


2020 Lau: Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2
https://wwwnc.cdc.gov/eid/article/26/7/20-0092_article


2020 Li: The divergence between SARS-CoV-2 and RaTG13 might be overestimated due to the extensive RNA modification
https://www.futuremedicine.com/doi/full/10.2217/fvl-2020-0066


2020 Liu: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2
https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173


2020 Paraskevis: Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event
https://www.sciencedirect.com/science/article/pii/S1567134820300447


2020 Xiao: Origin of coronavirus
https://www.scribd.com/document/447056518/Originsof2019-NCoV-XiaoB-Res


aht: New Evidence the US Did Bring COVID-19 to Wuhan During the Military Games
https://ahtribune.com/world/covid-19/3994-us-did-bring-covid-19-to-wuhan.html


2020 Zhang: "Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2" - Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak
https://www.cell.com/current-biology/pdfExtended/S0960-9822(20)30360-2


washpo: State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses
https://www.washingtonpost.com/opinions/2020/04/14/state-department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruses/


arabnews-may-28: "...between Oct. 7 and Oct. 24, no mobile phone data was recorded coming from part of the site thought to be the high-security National Biosafety Laboratory..."
https://www.arabnews.com/node/1672886/world


asiatimes-apr-06: Claims arose "Huang Yanling", a Wuhan lab worked was “patient zero” but Huang left in 2015, was in good health and never had covid-19.
https://asiatimes.com/2020/04/wuhan-lab-virus-leak-no-longer-discounted-cobra/


bbc: Most of us have heard that this virus "started" in a wildlife market in Wuhan. But the source of the virus - an animal with this pathogen in its body - was not found in the market.
https://www.bbc.com/news/science-environment-52529830


cntimes-mar-25-2020: It might have been the US army representatives to the Military World Games who brought the novel coronavirus to Wuhan in October 2019
https://www.globaltimes.cn/content/1183658.shtml


lab: The Long History of Accidental Laboratory Releases of Potential Pandemic Pathogens Is Being Ignored In the COVID-19 Media Coverage
https://www.independentsciencenews.org/health/the-long-history-of-accidental-laboratory-releases-of-potential-pandemic-pathogens


mace-e-pai: Telemetry data from the Wuhan BSL4 lab
https://www.documentcloud.org/documents/6884792-MACE-E-PAI-COVID-19-ANALYSIS-Redacted.html


nbcnews-may-08: The report — obtained by the London-based NBC News Verification Unit — says there was no cellphone activity in a high-security portion of the Wuhan Institute of Virology from Oct. 7 through Oct. 24, 2019, and that there may have been a "hazardous event" sometime between Oct. 6 and Oct. 11.
https://www.nbcnews.com/politics/national-security/report-says-cellphone-data-suggests-october-shutdown-wuhan-lab-experts-n1202716


nytimes-jan-08: "...a new virus..."
https://www.nytimes.com/2020/01/08/health/china-pneumonia-outbreak-virus.html


statnews-jan-24: Scientists in China sequenced the virus’s genome and made it available on Jan. 10, just a month after the Dec. 8 report of the first case of pneumonia from an unknown virus in Wuhan.
https://www.statnews.com/2020/01/24/dna-sleuths-read-coronavirus-genome-tracing-origins-and-mutations/


vox-jan-27: "... on January 20, Chinese President Xi Jinping made his first public statement on the outbreak..."
https://www.vox.com/2020/1/27/21082354/coronavirus-outbreak-wuhan-china-early-on-lancet


2021-CDC-Variants: Emerging SARS-CoV-2 Variants
https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html