U.S. government gave $3.7 million grant to Wuhan lab at cent

[admin]

Fight Over Covid’s Origins Renews Debate on Risks of Lab Work
by Carl Zimmer and James Gorman
New York Times
June 20, 2021

At a Senate hearing on efforts to combat Covid-19 last month, Senator Rand Paul of Kentucky asked Dr. Anthony S. Fauci whether the National Institutes of Health had funded “gain-of-function” research on coronaviruses in China.

“Gain-of-function research, as you know, is juicing up naturally occurring animal viruses to infect humans,” the senator said.

Dr. Fauci, the nation’s top infectious disease expert, flatly rejected the claim: “Senator Paul, with all due respect, you are entirely and completely incorrect, that the N.I.H. has not ever and does not now fund gain-of-function research in the Wuhan Institute.”

This exchange, and the bit of scientific jargon at the heart of it, has gained traction in recent weeks, usually by people suggesting that the coronavirus was engineered, rather than having jumped from animals to humans, the explanation favored by most experts on coronaviruses. The uproar has also drawn attention back to a decade-long debate among scientists over whether certain gain-of-function research is too risky to allow.

Spurred by some contested bird flu experiments in 2012, the U.S. government adjusted its policies for oversight of certain types of pathogen studies. But some critics in the scientific community say that the policy is overly restrictive and that its enforcement has been far from transparent.

The stakes of the debate could not be higher. Too little research on emerging viruses will leave us unprepared for future pandemics. But too little attention to the safety risks will increase the chances that an experimental pathogen may escape a lab through an accident and cause an outbreak of its own.

Sorting out the balance of risks and benefits of the research has proved over the years to be immensely challenging. And now, the intensity of the politics and rhetoric over the lab leak theory threatens to push detailed science policy discussions to the sidelines.

“It’s just going to make it harder to get back to a serious debate,” said Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health who has urged the government to be more transparent about its support of gain-of-function research.

read the rest of the nyt article ...

[admin]

Part 1 of 4

The Origins of COVID-19: An Investigation of the Wuhan Institute of Virology
by House Foreign Affairs Committee
Lead Republican Michael T. McCaul
Report Minority Staff
One Hundred Seventeenth Congress
August 2021

The National Institutes of Health (NIH) today [December 19, 2017] lifted a 3-year moratorium on funding gain-of-function (GOF) research on potential pandemic viruses such as avian flu, SARS, and MERS, opening the door for certain types of research to resume.

Donald Trump's tenure as the 45th president of the United States began with his inauguration on January 20, 2017 and ended on January 20, 2021.

-- Presidency of Donald Trump, by Wikipedia

“The Godfather of [gain-of-function virology research], the head of the pyramid, is a guy you may have heard of called Anthony Fauci,” Rogin said. “So, Anthony Fauci, the hero of the pandemic, is the most important person in the world of gain-of-function research there is . . . Basically, he is the one disbursing all the grants for this, he is the one who pushed to turn it back on after Obama turned it off, that’s another crazy story, he turned it back on without really consulting the White House.”

“He consulted the Office of Science and Technology Policy, which is part of the White House, but the White House put a pause on it and he undid the pause,” Rogin continued. “The details are a little sketchy. I’m not saying he did anything necessarily wrong or illegal, but I’m saying that a lot of people that I know inside the Trump administration had no idea that he had turned this back on. He found a way to turn it back on in the mess of the Trump administration because the Trump administration is full of a bunch of clowns, so you could get things done if you knew how to work the system.”

As Rogin himself admits, “the details are a little sketchy,” and we’ll have to take a look at the sourcing included in whatever article this piece of news appears in before alleging any wrongdoing.

-- Fauci Reportedly Relaunched NIH Gain-of-Function Research without Consulting White House, by Jack Crowe, National Review, April 27, 2021

The action coincides with today's release of a US Department of Health and Human Services (HHS) framework for guiding funding decisions about proposed research involving pathogens that have enhanced potential for creating pandemics.

Experts involved in the discussions welcomed the development, but some said the new framework still leaves key unanswered questions, such as how to responsibly report findings from the funded lab work in medical journals. Meanwhile, in research labs, some scientists plan to resume experiments and are relieved the pause has ended. Both groups are eager to see how the new review process works in real life.

In a statement today, NIH Director Francis Collins, MD, PhD, said "We have a responsibility to ensure that research with infectious agents is conducted responsibly, and that we consider the potential biosafety and biosecurity risks associated with such research." He added that he is confident that the review process spelled out in the new framework "will help to facilitate the safe, secure, and responsible conduct of this type of research in a manner that maximizes the benefits to public health."...

In light of controversial research on H5N1 viruses in 2012, the Obama administration in 2014 announced a pause of federally funded GOF research and asked a government advisory group to reevaluate federal GOF funding policies and put together recommendations to help officials make their decisions.

The expert group, called the National Science Advisory Board for Biosecurity (NSABB), commissioned a 1,000-page risk-benefit assessment to help them make their final guidance, which they finalized in June 2016, along with an ethics white paper. As part of the process, the NSABB held two National Academies symposia on GOF issues....

The framework, condensed into a 6-page document, spells out a multidisciplinary review process that involved the funding agency and a department-level review group that considers the merits and possible research benefits and the potential to create, transfer, or use an enhanced potential pandemic pathogen (PPP). In January in the final days of the Obama administration, the White House Office of Science and Technology Policy (OSTP) released guidance the departments can use to follow through with the reviews.

There are eight criteria in the framework for guiding HHS funding decisions, which stipulate, for example, that the research has been evaluated by an independent expert review as scientifically sound, that the potential risks and benefits are justified, that there are no other equally effective but less risky options for answering the research question, and that the research team and facility have the capacity to do the work safety and securely and to respond rapidly if there are any accidents, protocol lapses, or security breaches.

Regarding issues surrounding publication, the criterion says that the research results are expected to be responsibly communicated, based on applicable laws, regulations, and policies, along with terms and conditions of funding.

Also, the framework stipulates that the work will be done with the support of funding mechanisms that allow appropriate risk management and ongoing institution and federal oversight of the research. And finally, the criteria state that the research must be ethically justifiable...

Marc Lipsitch, PhD, professor of epidemiology and director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health, has been deeply involved in the GOF discussions and has argued for a much more rigorous approach for evaluating the experiments. He has pushed for experts to consider safer ways to assess potential pandemic virus threats and for an international approach to tackling the issues.

"My overall take is that this is a small step forward," he said, adding that it includes a department-level review of the most concerning types of research, which have been defined appropriately after extensive time and debate. "The question is how such reviews will play out in practice."

However, Lipsitch said one problem is that the guidance specifies that research groups that propose work with enhanced pathogens will need to convince reviewers that there is no feasible, equally effective alternative way of addressing the scientific question with a less risky approach.

"If this means no alternative to answer with certainty the question of whether a specific strain that occurs in nature can very easily evolve to acquire a ferret-transmissible phenotype, then this criterion will always be satisfied," he said. "This is a scientific question that can uniquely be answered with dangerous experiments, and cannot be answered safely. But it is not a very useful one, because every strain in nature is different."

Michael Osterholm, PhD, MPH, who was a member of the NSABB during the controversy over the H5N1 papers, said he believes the GOF work can be done safely, but he doesn't agree that scientists doing the federally funded work should be unfettered.

Osterholm said his main concern regards the public health implications of the publicly available details about how the work is communicated, which the new framework doesn't spell out. "How we detail that information needs to be considered," such as more finely specifying when findings are open to the general public, when they're disseminated on a "need to know" basis, and when the information is classified.

"Until we have that part solved, I'm concerned about the work being done," he said.

Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, which publishes CIDRAP News, added that some research is needed to answer key questions, such as what it would take for Ebola to become a respiratory virus, findings that would have implications for preparedness. "If it were the case, I don't want the public to have a blueprint on how to do it," he said.

Tom Inglesby, MD, director and chief executive officer at the Center for Health Security at Johns Hopkins Bloomberg School of Public Health, has also been deeply involved in discussions about issues related to the research pause. He said the requirements for the multidisciplinary, department-level pre-funding review and the involvement of the White House OSTP are excellent.

He added that the emphasis on enhanced potential pandemic pathogens is correct and focuses the framework on where it should be, such as on harmful consequences, immunity disruption, conferred resistance, and reconstructed extinct pathogens. "Though for the policy to be successful it needs to, at a minimum, be able to oversee the creation of novel strains that may be highly transmissible and highly virulent and should probably focus on that most intently to start."

A potentially serious weakness of the new framework is that surveillance activities involving potential pandemic pathogens (PPPs), including sampling and sequencing, aren't considered to be enhanced PPPs and would be exempt from reviews, Inglesby said, adding that surveillance as a rationale doesn't change potential risks of novel PPP strains. "There are serious debates about whether specific enhanced PPP projects are materially useful to on-the-ground surveillance programs," he said.

Inglesby's other concerns revolve around the lack of hard details of how the experiment reviews will work, such as the process for weighing the risks and benefits and the criteria for judging if researchers and institutions have the capacity to do the work safely. "I would have liked to see if this framework was working as intended before the moratorium was ended," he said, suggesting that agencies funding the work publish their experiences using the new framework to show how it functions.

-- Feds lift gain-of-function research pause, offer guidance, by Lisa Schnirring, December 19, 2017

TABLE OF CONTENTS: [PDF HERE]

• INTRODUCTION TO ADDENDUM TO THE FINAL REPORT
• EXECUTIVE SUMMARY
• GLOSSARY OF TERMS
• KEY PEOPLE
• ADDENDUM TO THE FINAL REPORT
o I. The City of Wuhan: Epicenter of a Pandemic
o II. Evidence of a Lab Leak
o III. Evidence of Genetic Modification
o IV. Evidence of a Lab Leak Cover-Up
o V. Hypothesis: A Lab Leak That Caused a Pandemic
o VI. Recommendations
o VII. Conclusion
o VIII. Appendix
• Timeline of the WIV Lab Leak and the Start of the COVID-19 Pandemic
• China Center for Disease and Control Memo on Supplementary Regulations
• JPCM Confidential Notice on the Standardization of the Management of Publication of Novel Coronavirus Pneumonia Scientific Research
• February 6, 2020, Email at 12:43am from Peter Daszak to Ralph Baric, Linfa Wang, and Others Inviting Them to Sign the Statement
• February 6, 2020, Email at 3:16pm from Peter Daszak to Ralph Baric Relaying Wang’s Request Not to Sign the Statement
• February 8, 2020, Email at 8:52pm from Peter Daszak to Rita Colwell Alleging WIV Researchers Requested the Statement

Introduction

Five hundred and four days ago, on March 16, 2020, Committee Minority Staff began its investigation into the origins of SARS-CoV-2 and the COVID-19 global pandemic at the direction of Ranking Member Michael T. McCaul. The House Foreign Affairs Committee Minority Staff Final Report on The Origins of the COVID-19 Global Pandemic, Including the Roles of the Chinese Communist Party and the World Health Organization was published in late September 2020. At the time of its release, there were an estimated 30.8 million cases of COVID-19 around the world, and a death toll of approximately 958,000. Today, the cumulative count stands at more than 196.4 million cases and 4,194,061 dead.

The House Foreign Affairs Committee Minority Staff has continued to investigate the origins of COVID-19, examining new information as it became available, including through expert testimony. We have done so because approximately 48 million of our population are under the age of 12 and without access to a vaccination, while others remain unvaccinated due to underlying medical conditions, leaving a large portion of American citizens at risk of infection. We prepared this addendum as reports increase regarding various strains around the globe, and as PRC authorities continue to withhold critical information about the early months of the pandemic. We have strongly urged our Majority colleagues to take this investigation seriously and conduct a full bipartisan investigation into the origins of COVID-19, and will continue to do so. President Biden has said he wants to discover how the pandemic began, and it is our duty to the American people to use all the tools in our arsenal in pursuit of that goal. As always, we stand ready to address this and other foreign policy challenges together and in a bipartisan manner. We must not let up on pressing General Secretary Xi and CCP authorities for answers.

Here we share the result of these efforts in an addendum to our September 2020 Final Report. In particular, this update focuses on whether the virus may have leaked from a medical research laboratory in Wuhan, Hubei Province, PRC, and the efforts to conceal such a leak. The evidence used to inform this report is based upon open source information and includes published academic work, official PRC publications (both public and confidential), interviews, emails, and social media postings.

Since the publication of the September 21, 2020 Final Report new questions have been raised pertaining to the origins of COVID-19. The PRC’s continued lack of transparency resulted in President Joseph R. Biden, Jr.’s May 26, 2021, order to the United States Intelligence Community to prepare a report in 90 days on the origins of COVID-19, “including whether it emerged from human contact with an infected animal or from a laboratory accident.”1 [“Statement by President Joe Biden on the Investigation into the Origins of COVID-19.” The White House, 26 May 2021, http://www.whitehouse.gov/briefing-room ... -covid-19/.]

Based on the material collected and analyzed by the Committee Minority Staff, the preponderance of evidence suggests SARS-CoV-2 was accidentally released from a Wuhan Institute of Virology laboratory sometime prior to September 12, 2019. The virus, or the viral sequence that was genetically manipulated, was likely collected in a cave in Yunnan province, PRC, between 2012 and 2015. Researchers at the WIV, officials within the CCP, and potentially American citizens directly engaged in efforts to obfuscate information related to the origins of the virus and to suppress public debate of a possible lab leak. It is incumbent on these parties to respond to the issues raised herein and provide clarity and any exonerating evidence as soon as possible. Until that time, it must be assumed General Secretary Xi and the Chinese Communist Party, prioritizes preserving the Party over the lives of its own people and those around the global suffering the effects of the COVID-19 pandemic.

Executive Summary

More than one year after the World Health Organization declared a pandemic, the world is still reeling from the emergence of the SARS-CoV-2 virus and the disease it causes, COVID-19. More than four million people have lost their lives worldwide, including more than 612,000 Americans, while economies around the world have been devastated by the fallout. This report investigates the origin of this virus and looks at how it became a deadly pandemic.

The Wuhan Institute of Virology

Last September, the House Foreign Affairs Committee Minority Staff, under the direction of Ranking Member Michael T. McCaul, released a report on the origins of the COVID-19 pandemic. That report highlighted the possibility SARS-CoV-2 could have leaked from the Wuhan Institute of Virology (WIV). However, as we continued our investigation and uncovered more information, we now believe it’s time to completely dismiss the wet market as the source of the outbreak. We also believe the preponderance of the evidence proves the virus did leak from the WIV and that it did so sometime before September 12, 2019.

This is based upon multiple pieces of evidence laid out in the report, including:

• The sudden removal of the WIV’s virus and sample database in the middle of the night on September 12, 2019 and without explanation;
• Safety concerns expressed by top PRC scientists in 2019 and unusually scheduled maintenance at the WIV;
• Athletes at the Military World Games held in Wuhan in October 2019 who became sick with symptoms similar to COVID-19 both while in Wuhan and also shortly after returning to their home countries;
• Satellite imagery of Wuhan in September and October 2019 that showed a significant uptick in the number of people at local hospitals surrounding the WIV’s headquarters, coupled with an unusually high number of patients with symptoms similar to COVID-19;
• The installation of a People’s Liberation Army’s bioweapons expert as the head of the WIV’s Biosafety Level 4 lab (BSL-4), possibly as early as late 2019; and
• Actions by the Chinese Communist Party and scientists working at or affiliated with the WIV to hide or coverup the type of research being conducted at there.

Genetic Modification

This report also lays out ample evidence that researchers at the WIV, in conjunction with U.S. scientists and funded by both the PRC government and the U.S. government, were conducting gain-of-function research on coronaviruses at the WIV, at times under BSL-2 conditions. Much of this research was focused on modifying the spike protein of coronaviruses that could not infect humans so they could bind to human immune systems. The stated purpose of this work was to identified viruses with pandemic potential and to create a broad-spectrum coronavirus vaccine. In many instances, the scientists were successful in creating “chimeric viruses” -– or viruses created from the pieces of other viruses –- that could infect human immune systems. With dangerous research like this conducted at safety levels similar to a dentist’s office, a natural or genetically modified virus could have easily escaped the lab and infected the community.

Committee Minority Staff has also identified scientists who are directly tied to the WIV, and who worked on gain-of-function research in the years prior to the start of the current pandemic, who had the ability to modify genetically modify coronaviruses without leaving any trace evidence. An American scientist, Dr. Ralph Baric, assisted in creating a method to leave no trace of genetic modification as early as 2005. And as early as 2016, scientists working at the WIV were able to do the same. This makes it clear that claims by the scientific community that SARS-CoV-2 could not be man-made because it has no genetic modification markers are disingenuous.

We conclude there is ample proof that the virus could have been genetically manipulated, and that it is vitally important we fully investigate this hypothesis to determine if that happened here.

The Cover-Up

In the original report, we laid out many of the ways the Chinese Communist Party (CCP) and the World Health Organization (WHO) went to great lengths to cover up the initial epidemic, and how their cover-up likely turned what could have been a local outbreak into a global pandemic. The CCP detained doctors in order to silence them, and disappeared journalists who attempted to expose the truth. They destroyed lab samples, and hid the fact there was clear evidence of human-to-human transmission. And they still refuse to allow a real investigation into the origins. At the same time, the WHO, under Director General Tedros, failed to warn the world of the impending pandemic. Instead, he parroted CCP talking points, acting as a puppet of General Secretary Xi.

In this addendum, we have uncovered further evidence of how top scientists at the WIV and Dr. Peter Daszak, an American scientist, furthered that cover-up. Their actions include bullying other scientists who questioned whether the virus could have leaked from a lab; misleading the world about how a virus can be modified without leaving a trace; and, in many, instances directly lying about the nature of the research they were conducting, as well as the low-level safety protocols they were using for that research.

These actions not only delayed an initial investigation into the possibility of a lab leak costing valuable time, but provide further proof the virus likely leaked from the WIV. These actions also call into question the way in which U.S. government grants are used in overseas labs and call for more oversight of those grants.

Next Steps

After this extensive investigation, we believe it is time to call Peter Daszak to testify before Congress. There are still many outstanding questions about the type of research he funded at the WIV that only he can answer. In addition, we believe there is legislation Congress can pass that would not only hold those responsible accountable but also help to prevent a future pandemic, including but not limited to:

• Institute a ban on conducting and funding any work that includes gain-of-function research until an international and legally binding standard is set, and only where that standard is verifiably being followed.
• Sanction the Chinese Academy of Sciences and affiliated entities.
• List the Wuhan Institute of Virology and its leadership on the Specially Designated Nationals and Blocked Persons List and apply additional, appropriate secondary sanctions.
• Authorize new sanctions for academic, governmental, and military bioresearch facilities that fail to ensure the appropriate levels of safety and information sharing.

GLOSSARY OF TERMS

Gain-of-Function Research: “Research that improves the ability of a pathogen to cause disease.” – U.S. Department of Health and Human Services

Spike Protein: A protein structure on the surface of an enveloped virus responsible for anchoring the virus to the host cell’s surface and enabling the injection of the virus’ genetic material into the host cell.

RBD: Receptor-Binding Domain. The specific short fragment in a spike protein of a virus that binds the virus to a specific receptor on the host cell.

Primary Author: The first listed author of an academic paper, usually the person who contributes the most to a paper.

Corresponding Author: The point of contact for editors and outside readers who have questions about an academic paper.

USAID Predict: An epidemiological research grant program funded by the United States Agency for International Development. PREDICT provided funding for biological sampling aimed at virus identification and collection. The program provided grant funding to EcoHealth Alliance.

SARS: Severe Acute Respiratory Syndrome. A viral respiratory disease caused by SARS-CoV, a betacoronavirus. First identified as the cause of a 2002-2003 epidemic.

MERS: Middle East Respiratory Syndrome. A viral respiratory disease caused by MERS-CoV, a betacoronavirus. First identified as the cause of a 2012 outbreak.

SARS-CoV-2: The betacoronavirus that causes COVID-19.

Coronavirus: An RNA virus that causes disease in mammals and birds. Range in severity from the common cold to SARS-CoV-2.

Betacoronavirus: One of the four subclassifications of coronaviruses. Found in bats and rodents, this is the genus includes SARS, MERS, and SARS-CoV-2.

Biosafety Level 1 (BSL1): Designed for work on microbes not known to cause disease in healthy adults and present minimal potential hazard to laboratorians and the environment. Work can be performed on an open lab bench or table.

Biosafety Level 2 (BSL2): For work with microbes that pose moderate hazards to laboratorians and the environment. The microbes are typically indigenous and associated with diseases of varying severity. Personal protective equipment includes lab coats and gloves. Work can be performed in the open or in a biological safety cabinet. Commonly compared to the level of safety observed in a dentist’s office.

Bio Safety Level 3 (BSL3): For work with microbes that are either indigenous or exotic, and that can cause serious or potentially lethal disease through respiratory transmission. Respiratory transmission is the inhalation route of exposure. Researchers should be under medical surveillance and potentially immunized for the microbes they work with. Respirators may be required, in addition to standard personal protective equipment. Work must be performed within a biological safety cabinet. Exhaust air cannot be recirculated, and the laboratory must have sustained directional airflow by drawing air into the laboratory from clean areas towards potentially contaminated areas.

Biosafety Level 4 (BSL4): This is the highest level of biological safety. The microbes in a BSL-4 lab are dangerous and exotic, posing a high risk of aerosol-transmitted infections. Infections caused by these microbes are frequently fatal and without treatment or vaccines. Researchers must change clothing prior to entering the lab, shower upon exiting, and decontaminate all materials before exiting. All work with microbes must be performed in a Class III biological safety cabinet or while wearing a full body, air-supplied, positive pressure suit. The lab must be in a separate building or in a restricted zone, and must have a dedicated supply and exhaust air, as well as vacuum lines and decontamination systems.

Wuhan Institute of Virology (WIV): A research institute in Wuhan, PRC focused on focused on virology, that consists of at least two facilities – the Wuhan National Biosafety Laboratory and the Wuhan Institute of Virology Headquarters.”

Wuhan National Biosafety Laboratory: The WIV’s new campus, located in the Zhengdian Scientific Park in Jiangxia District, Wuhan. The location of the WIV’s Biosafety Level 4 laboratory space.

WIV Headquarters: The older WIV facility, located in Wuchang District, Wuhan near the Wuhan Branch of the Chinese Academies of Science.

Chinese Academy of Sciences: The national academy for natural sciences in the PRC. Reports to the State Council of the People’s Republic of China.

WIV1: The first novel coronavirus isolated by WIV researchers. Isolated from bat fecal samples in 2013. A SARS like coronavirus.

WIV16: The second coronavirus isolated by WIV researchers. Isolated from a single bat fecal sample in 2016. A SARS like coronavirus.

Rs4874: The third coronavirus isolated by WIV researchers. Isolated from a single bat fecal sample in 2017. A SARS like coronavirus.

ID4491/RaTG13: A SARS like coronavirus collected in 2013 in a mining cave. 96.1% similar to SARS-CoV-2.

ACE2: Angiotensin-converting enzyme-2, found on the surface of certain cells in a variety of animals, including humans, mice, and civets. The entry point for coronaviruses.

hACE2: The human version of ACE2. Primarily found on the surface of cells and tissues throughout the human body, including the nose, mouth, and lungs. In the lungs, hACE2 is highly abundant on type 2 pneumocytes, an important cell type present in chambers within the lung called alveoli, where oxygen is absorbed, and waste carbon dioxide is released. The primary entry point for SARS-CoV-2 into human cells.

Chimeric Virus: An artificial, man-made virus. Created by joining two or more viral fragments.

Natural Virus: A virus found in nature; “wild type.”

Reverse Genetics System: A method in molecular genetics that is used to help understand the function(s) of a gene by analyzing the phenotypic effects caused by genetically engineering specific nucleic acid sequences within the gene. Can be used to create chimeric viruses indistinguishable from natural viruses.

Furin Cleavage Site: An enzyme in the spike protein of SARS-CoV-2 that increases how infectious the virus is in humans. SARS-CoV-2 is the only betacoronavirus to have this structure.

Phylogenetic Analysis: The study of the evolutionary development of a species or a group of organisms or a particular characteristic of an organism. Used to identify the relationship between different viruses in the same family.

CGG Double Codon: “CGG-CGG.” This group of six nucleotides (a group of three nucleotides is also know as a codon) is half of the 12 nucleotides that create the furin cleavage site. The CGG double codon is relatively rare in coronaviruses, and SARSCoV- 2 is the only coronavirus in its family to have one.

KEY PEOPLE

Dr. Wang Yanyi: Director General of the Wuhan Institute of Virology.

Dr. Yuan Zhiming: Director of the WNBL BSL-4 lab. General Secretary of the Chinese Communist Party Committee within the Wuhan Branch of the Chinese Academy of Sciences, to which the WIV belongs.

Dr. Shi Zheng-li: Senior scientist as the Wuhan Institute of Virology (WIV). Serves as Director, Research Center for Emerging Infectious Diseases; Director, Chinese Academy of Sciences Key Laboratory of Special Pathogens; Director, Biosafety Working Committee; and Deputy Director of the Wuhan National Biosafety Laboratory’s Biosafety-Level 4 lab.

Dr. Ben Hu: WIV researcher and former doctoral student of Shi Zheng-li. Deeply involved in the WIV’s coronavirus research.

Dr. Linfa Wang: PRC national, Director and Professor of the Program in Emerging Infectious Diseases at the Duke-NUS Graduate Medical School in Singapore. Chair of the Scientific Advisory Board for the Center for Emerging Diseases at the WIV.

Dr. Peter Daszak: CEO of EcoHealth Alliance. Longtime collaborator of Shi and others at the WIV. Provided subgrants to the WIV to help fund coronavirus research.

Dr. Ralph Baric: Researcher at the University of North Carolina at Chapel Hill who has collaborated with Shi and other WIV researchers on coronavirus research.

ADDENDUM TO THE REPORT

I. THE CITY OF WUHAN: EPICENTER OF A PANDEMIC

Wuhan is the epicenter of the coronavirus pandemic. Located in central PRC where the Yangtze River, the PRC’s longest river, and the Han River meet, Wuhan is the capital city of Hubei Province and boasts a population of about 11.1 million in about 3,280 square miles. [2] [“WHO-convened Global Study of Origins of SARS-CoV-2: China Part.” Joint WHO-China Study. 30 March 2021, https://www.who.int/health-topics/coron ... -the-virus] It is home to the PRC’s tallest skyscrapers, multiple colleges and universities, including the prominent Wuhan University, major historical and cultural sites, and an influential research laboratory, the Wuhan Institute of Virology (WIV). To put the scale of Wuhan in perspective, the city covers an area five times the size of Houston and has a larger population than New York City and Chicago combined.

Wuhan is home to the Hankou railway station, central PRC’s biggest European-style Railway station, and two other major train stations. Hankou Station connects directly to the Tianhe International Airport, the busiest airport in central PRC and the geographic center of the PRC’s airport network. From the Tianhe airport, travelers can fly direct to New York City, San Francisco, Paris, Milan, Rome, Hamburg, Bangkok, Tokyo, Seoul, and Dubai, among many other destinations around the world.

The PRC calls Wuhan one of its nine “National Central Cities,” an official state label that means it leads the way, along with the capital Beijing, Shanghai, and other major cities, in developing culture, politics, and the economy. [3] [Xu, Zongwei. “China Unveils National Central City Strategy.” China Watch, 29 Mar. 2018, http://www.chinawatch.cn/a/201803/29/WS ... 67c6c.html.] An August 2016 report by the Netherlands Enterprise Agency, a government agency that operates under the auspices of the Ministry of Economic Affairs and Climate Policy, identified Wuhan as a major hub not just within the PRC, but also globally within the Chinese “One Belt One Road” initiative due to its accessibility. [4] [Van de Bovenkamp, Judith and Yuan Fei. “Economic Overview of Hubei Province.” Neatherlands Business Support Office Wuhan, Aug. 2016, https://www.rvo.nl/sites/default/files/ ... -China.pdf] The city is also home to significant railway commerce. A 2018 report from Xinhua news expected an estimated 500 freight trains from Wuhan to Europe for the export of goods. [5] [“Central China-Europe Rail Freight to Surge in 2018.” Xinhua, 1 Feb. 2018. http://www.china.org.cn/china/Off_the_Wire/2018- 02/01/content_50372222.htm]

France, the U.S., the Republic of Korea, and the UK maintain Consulates in the city, which was selected to host the 7th International Military Sports Council (CISM) Military World Games. During the games, more than 9,000 military personnel from over 100 countries stayed in Wuhan in accommodations at an athletes’ village built specifically for the games.

II. EVIDENCE OF A LAB LEAK

As discussed in the previously issued report, the WIV continues to be a focal point of debate concerning the origins of SARS-CoV-2 and the COVID-19 pandemic. In recent months, new information about the WIV has come to light, enabling us to better understand the institute, the type of research conducted by scientists working there, and its ties to the CCP and their military, the People’s Liberation Army (PLA). We now believe the preponderance of evidence shows the virus accidentally leaked from one of the WIV’s facilities.

The Wuhan Institute of Virology

The WIV was founded in 1956 as the Wuhan Microbiology Laboratory and has operated under the administration of the Chinese Academy of Sciences since 1978. [6] [“History.” Wuhan Institute of Virology, http://english.whiov.cas.cn/About_Us2016/History2016/.] The institute currently occupies at least two campuses – the much-discussed Wuhan National Biosafety Laboratory (WNBL) in Zhengdian Scientific Park (see Figure 1), and the older facility (hereafter WIV Headquarters) located in the Xiaohongshan park in the Wuchang District of Wuhan (see Figure 2). The WNBL is a large complex with multiple buildings that house 20 Biosafety Level II (BSL-2) laboratories, two Biosafety Level III (BSL-3) laboratories, and 3000 square meters of Biosafety Level IV (BSL-4) space, “including four independent laboratories areas and two animal suites.” [7] [World Health Organization. “WHO Consultative Meeting on High/Maximum Containment (Biosafety Level 4) Laboratories Networking.” Meeting Report, Lyon, France, 13-15 Dec. 2018. https://apps.who.int/iris/bitstream/han ... HO-WHECPI- 2018.40-eng.pdf] Construction was completed in 2015, but due to delays the BSL-4 space did not become operational until early 2018. [8] [Zhiming, Yuan. “Current status and future challenges of high-level biosafety laboratories in China.” Journal of Biosafety and Biosecurity, 1 Sept. 2019, 1(2): 123-127. https://doi.org/10.1016/j.jobb.2019.09.005]


Fig. 1: Wuhan National Biosafety Laboratory (WNBL)

Missing from the majority of public debates regarding the WIV is the research conducted at the WIV Headquarters, the older location in the Wuchang District of Wuhan. Located 12 miles northeast of the WNBL, in the Wuchang District, this facility remains the administrative headquarters of the WIV. In addition to the BSL-2 labs at this location, the WIV constructed a BSL-3 laboratory at the facility in 2003. [9] [Zheng Qianli, “Jiang Xia plays new essays and plays Yoko on the crane——The construction and research team of P4 laboratory of Wuhan Institute of Virology, Chinese Academy of Sciences.” Chinese Journal of Science, 1 Jan. 2018, https://archive.is/V3GHk#selection-517.35-517.202]

It was here, in the center of Wuhan, that Dr. Shi Zheng-li and her team conducted gain-of-function research on coronaviruses in the years leading up to the COVID-19 pandemic.


Fig. 2: WIV Headquarters in Wuchang

According to the WIV’s website, Shi Zheng-li serves as the Director of the WIV’s Research Center for Emerging Infectious Diseases, the Deputy Director of the WNBL BSL-4 lab, the Director of the BSL-3 lab, and the Director of the Biosafety Working Committee. [10] [“Shi Zhingli.” Wuhan Institute of Virology, http://www.whiov.cas.cn/sourcedb_whiov_ ... 00074.html] Shi is also the Director of the Chinese Academy of Sciences (CAS) Key Laboratory of Special Pathogens and Biosafety, [11] [“Prof. SHI Zhengli elected a fellow of the American Academy of Microbiology.” Wuhan Institute of Virology, http://english.whiov.cas.cn/ne/201903/t ... 06697.html] which includes the majority of scientists who are conducting gain-of-function research on coronaviruses at the WIV.

It should be noted that the WIV has a Chinese Communist Party Committee within the institute, as well as a Commission for Discipline Inspection. The Party Committee is divided into four party branches, which are then divided into subbranches organized around the individual WIV departments, research centers, and offices. Each subbranch has its own Propaganda Committee. Committee Minority Staff were able to identify eight WIV researchers on these committees, including several who are affiliated with the Key Laboratory that Shi directs.

Table 1: WIV Researchers on CCP Propaganda Committees

WIV Researcher / Lab Affiliation / Propaganda Committee [12] [“Party Branch.” Wuhan Institute of Virology, http://www.whiov.cas.cn/djkxwh/dqzz/dzb/]

Liu Qiaojiue / Key Laboratory of Special [13] [Wang Q, et. al. “Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.” Cell, 23 July 2020, 182(2):417-428.e13, https://pubmed.ncbi.nlm.nih.gov/32526208/] Pathogens and Biosafety / Party Branch of Research Center for Emerging Infectious Diseases

Zhang Xiaowei / Key Laboratory of Special [14] [Zhang, Xiaowei et al. “Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.” Journal of Neuroinflammation, 30 Aug. 2016, 13(1):209. https://pubmed.ncbi.nlm.nih.gov/27576490/] Pathogens and Biosafety and Key Laboratory of Virology / Party Branch of the Research Center for Microbiology and Nanobiology

Shen Xurui / Key Laboratory of Special Pathogens and Biosafety [15] [Zhou, Peng et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature March 2020, 579(7798): 270- 273. https://pubmed.ncbi.nlm.nih.gov/32015507/] / Graduate Party Branch of the Research Center for Emerging Infectious Diseases

Tang Shuang / State Key Laboratory of Virology [16] [Abudurexiti, Abulikemu, et al. “Taxonomy of the order Bunyavirales: update 2019.” Archives of Virology, July 2019, 164(7): 1949-1965. https://pubmed.ncbi.nlm.nih.gov/31065850/] / Party Branch of the Research Center for Microbial Resources and Bioinformatics

Wu Yan / State Key Laboratory of Virology [17] [Su, Hai-Xia et al. “Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.” Acta Pharmacologica Sinica, September 2020, 41(9): 1167-1177. https://pubmed.ncbi.nlm.nih.gov/32737471/] Party Branch of Molecular Virus and Pathology Research Center

He Lihong / State Key Laboratory of Virology [18] [Shao, Wei et al. “Functional Characterization of the Group I Alphabaculovirus Specific Gene ac73.” Virologica Sinica, Dec. 2019, 34(6): 701-711. https://pubmed.ncbi.nlm.nih.gov/31317397/] / Party Branch of the Research Center for Microbial Resources and Bioinformatics

Wang Qingxing / State Key Laboratory of Virology [19] [Su, Haixia et al. “Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease.” Nature Communications, 15 June 2021, (2(1): 3623. https://pubmed.ncbi.nlm.nih.gov/34131140/] / Graduate Party Branch of the Research Center for Molecular Viruses and Pathology

Yang Mengsi / State Key Laboratory of Virology [20] [Zhang, Juan, et. al. “Passive cancer targeting with a viral nanoparticle depends on the stage of tumorigenesis.” Nanoscale, 8 July 2021, 13(26):11334-11342, https://pubmed.ncbi.nlm.nih.gov/34165123/] / Graduate Party Branch of the Research Center of Microbiology and Nanobiology

The Committee for Discipline Inspection is charged with “the implementation of the party's line, policy, party discipline, relevant laws and regulations, and the institute's rules and regulations.” [21] [“Commission for Discipline Inspection.” Wuhan Institute of Virology, http://www.whiov.cas.cn/djkxwh/dqzz/jw/]

In addition to the researchers serving on propaganda committees, other key figures at the WIV also serve as CCP officials. Dr. Wang Yanyi serves as the Director of the WIV and joined the China Zhi Gong Party, a CCP controlled minority party, in 2010. In 2018, the same year she became the Director General of the WIV, she was elected the Deputy Director of the Wuhan Municipal Party Committee.

Until late 2019, the BSL-4 lab was managed by Dr. Yuan Zhiming. Yuan is the General Secretary of the Chinese Communist Party Committee within the Wuhan Branch of the Chinese Academy of Sciences, to which the WIV belongs. Local CCP leaders not only run the WIV itself but also directly managed the BSL-4 lab. [22] [Izambard, Antoine. “L'histoire Secrète Du Laboratoire P4 De Wuhan Vendu Par La France à La Chine.” Challenges, 30 Apr. 2020 http://www.challenges.fr/entreprise/san ... a-lachine_ 707425.]

Director Wang’s 2021 New Year’s speech makes reference to the Party Committee of Wuhan Institute of Virology, pledging that the party committee will “effectively play the role of a battle fortress of grassroots party organizations.” [23] [“New Year's Speech by the Director in 2021.” Wuhan Institute of Virology, http://www.whiov.cas.cn/gkjj/szzc_160220/] The WNBL also has its own party branch, the Zhengdian Laboratory Party Branch, which was “awarded the title of ‘Red Flag Party Branch’ by the Hubei Provincial Party Committee and Provincial Organization Working Committee, effectively playing an advanced and exemplary role.” [24] [“New Year’s Message from the Director in 2020.” Wuhan Institute of Virology, https://web.archive.org/web/20200701032 ... zc_160220/] Notably, in discussing the COVID-19 pandemic, Director Wang’s 2021 speech takes pains to address questions of lab safety – “The institute's high-level biosafety laboratory operates safely for more than 300 days throughout the year.” [25] [Ibid.] Her 2020 address, posted sometime after April 2020, makes no such mention.

The WNBL’s BSL-4 lab was constructed as a result of an agreement between the PRC and France that was signed after the 2003 SARS pandemic. [26] [“About WIV.” Wuhan Institute of Virology, http://english.whiov.cas.cn/About_Us201 ... ction2016/.] At the time, all BSL-3 labs in the PRC were controlled by the PRC’s People’s Liberation Army (PLA). Then-President of France, Jacques Chirac, and his Prime Minister, Jean-Pierre Raffarin, approved the project despite concerns from both the French Ministry of Defense and French intelligence services – Raffarin himself described it as “a political agreement.” [27] [Izambard, Antoine. “L'histoire Secrète Du Laboratoire P4 De Wuhan Vendu Par La France à La Chine.” Challenges, 30 Apr. 2020, http://www.challenges.fr/entreprise/san ... a-lachine_ 707425.] The PRC was suspected of having a biological warfare program, and the military and intelligence services were worried that the dual-use technology required to build a BSL- 4 lab could be misused by the PRC government. The uneasy compromise reached within the French government was that the agreement would require joint PRC-France research to be conducted in the lab, with French researchers present. [28] [Ibid.]

In 2016, the PRC requested dozens of the containment suits required to work in the lab. The French Dual-Use Commission, tasked with considering exports of sensitive equipment, rejected their request. According to French reporting, the request was “well above the needs of the Wuhan [lab].” [29] [Ibid.] This continued to fuel concerns within the French Ministry of Defense that the PRC was seeking to engage in military research or open a second BSL-4 lab for military means. Despite the agreement that the BSL-4 lab would be a site of joint research, and an announcement at the 2017 inauguration by then Prime Minister Bernard Cazeneuve of €5 million in funding, there has only been one French scientist assigned to the lab. His tour ended in 2020. [30] [Izambard.]

Safety Concerns and Unusual Maintenance

There have been several reports of safety concerns at PRC labs starting as early as 2004, when it was discovered SARS leaked from a lab in Beijing. Several other accidental releases have happened in the years since.

As discussed in our original report released last year, in 2018 U.S. State Department officials sent cables to Washington, D.C. highlighting concerns with safety issues at the WIV. The cables reported that scientists at the WIV noted “a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.” [31] [Rogin, Josh. “Opinion | State Department Cables Warned of Safety Issues at Wuhan Lab Studying Bat Coronaviruses.” The Washington Post, 14 Apr. 2020, http://www.washingtonpost.com/opinions/ ... -wuhanlab- studying-bat-coronaviruses/.] The cables also questioned the PRC’s commitment to prioritizing the important research for which the lab was designed.


Fig. 4: Excerpt from January 19, 2018 Cable from the U.S. Embassy in Beijing to State Department Headquarters in Washington, D.C.

(b)(6) [DELETE] Thus, while the BSL-4 lab is ostensibly fully accredited, its utilization is limited by lack of access to specific organisms and by opaque government review and approval processes. As long as this situation continues, Beijing's commitment to prioritizing infectious disease control -- on the regional and international level, especially in relation to highly pathogenic viruses, remains in doubt.

One year later, in June 2019, George Gao, the Director of the Chinese Center for Disease Control and Prevention, expressed concerns about safety protocols at the WIV. In an almost prophetic statement published in Biosafety and Health, Gao wrote (emphasis added):

Advances in biomedical technologies, such as genome editing and synthetic biotechnology, have the potential to provide new avenues for biological intervention in human diseases. These advances may also have a positive impact by allowing us to address risks in new approaches. However, the proliferation of such technologies means they will also be available to the ambitious, careless, inept, and outright malcontents, who may misuse them in ways that endanger our safety. For example, while CRISPR-related techniques provide revolutionary solutions for targeted cellular genome editing, it can also lead to unexpected off-target mutations within genomes or the possibility of gene drive initiation in humans, animals, insects, and plants. Similarly, genetic modification of pathogens, which may expand host range as well as increase transmission and virulence, may result in new risks for epidemics. For example, in 2013, several groups showed that influenza H5N1 viruses with a few nucleotide mutations and H7N9 isolates reasserted with 2009 pandemic H1N1 virus could have the ability for airborne transmission between ferrets. Likewise, synthetic bat-origin SARS-like coronaviruses acquired an increased capability to infect human cells. Thus, modifying the genomes of animals (including humans), plants, and microbes (including pathogens) must be highly regulated. [32] [Gao, George F. “For a better world: Biosafety strategies to protect global health.” Biosafety and Health, June 2019, 1(1): 1-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147920/]

Three months later, in September 2019, Yuan Zhiming, the Director of the BSL-4 lab at the WNBL and Shi’s superior, published an article in the Journal of Biosafety and Biosecurity.

Entitled, “Current status and future challenges of high-level biosafety laboratories in China,” [33] [Yuan Zhinming. “Current status and future challenges of high-level biosafety laboratories in China.” Journal of Biosafety and Biosecurity, Sept. 2019, 1(2): 123-127. https://www.sciencedirect.com/science/a ... 0391#b0080] the article discusses at length the construction of the WNBL. Yuan identifies multiple key issues, including inadequate biosafety management systems, insufficient resources for efficient laboratory operation, and deficiency of professional capacity. With a surprising level of transparency, Yuan admits that the enforcement of pathogen, waste, and laboratory animal management regulations “needs to be strengthened.” [34] [Ibid.] Discussing the insufficient level of resources being provided by the PRC government, he stated:

The maintenance cost is generally neglected; several high-level BSLs have insufficient operational funds for routine yet vital processes. Due to the limited resources, some BSL-3 laboratories run on extremely minimal operational costs or in some cases none at all. [35] [Ibid.]

Yuan also raised concerns about a lack of specialized biosafety managers and engineers to run the labs. [36] [Ibid.] It is important to note that researchers at the WIV had previously conducted gain-of-function research on coronaviruses at the BSL-2 and BSL-3 levels. This is important given that both the head of the China CDC and the head of the WIV’s BSL-4 labs had expressed concern about the safety of this research and the labs in which it was being conducted.

Interestingly, there appears to have been ongoing maintenance and repairs projects occurring at the WIV in 2019, before Yuan published his article raising these concerns. It is important to note that at the time of the hazardous waste treatment system renovation project, the WNBL had been operational for less than two years. Such a significant renovation so soon after the facility began operation appears unusual. Procurement announcements published on the PRC’s government procurement website provide evidence of ongoing work at what appears to be both WIV locations.

Table 2: WIV Procurement Projects in 2019

Project Name / Location / Date / Budget (USD)

Maintenance Project of P3 Laboratory and Laboratory Animal Center in Zhengdian Park [37] [“Announcement of Competitive Consultation on Maintenance Project of P3 Laboratory and Laboratory Animal Center in Zhengdian Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 1 March 2019, https://archive.is/7eCPU#selection-229.0-229.185] / WNBL / March 1, 2019 / $401,284.10

Procurement of Positive Pressure Protective Clothing [38] [“Announcement of a single source for the purchase of positive pressure protective clothing project by Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 21 March 2019, https://archive.is/VUcNA#selection-229.0- 229.157] / WNBL / March 21, 2019 / $177,161.40

Hazardous Waste Treatment System Renovation Project [39] [ “Announcement on the transaction of the hazardous waste treatment system renovation project in Zhengdian Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 31 July 2019, https://archive.is/3CW03#selection- 229.0-229.166] / WNBL / July 31, 2019 / $1,521,279.28

Procurement Project of The Environmental Air Disinfection System and The Scalable Automated Sample Storage Management System [40] [“Announcement of winning the bid for the procurement project of the environmental air disinfection system and the scalable automated sample storage management system of the Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 14 Aug. 2019, https://archive.is/1nXLD#selection-229.0-229.228] / Unclear / August 14, 2019 / $132,200,025.47

Security Service Procurement Project [41] [“Competitive consultation on the procurement project of security services in Zhengdian Science Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 12 Sept. 2019,https://archive.is/tUi75#selection-229.0- 229.156] / WNBL / September 12, 2019 / $1,281,022.33

Central Air Conditioning Renovation Project [42] [“Competitive Consultation on Central Air Conditioning Renovation Project of Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 16 Sept. 2019, https://archive.is/bfoTD#selection-229.0-229.131] / Unclear / September 16, 2019 / $606,382,986.11

Procurement of Air Incinerator and Testing Service [43] [“The Wuhan Institute of Virology of the Chinese Academy of Sciences plans to use a single-source procurement method to publicize the procurement of air incineration devices and test service projects.” China Government Procurement Network, 3 Dec. 2019, https://archive.is/Jifqr#selection-229.0-229.197] / Unclear / December 3, 2019 / $49,388.81

The references to maintenance at the BSL-3 and animal center at the WNBL, the procurement of an environmental air disinfection system, and renovations to the hazardous waste treatment system and central air conditioning system all raise questions about how well these systems were functioning in the months prior to the outbreak of COVID-19.

The Disappearing Database

On September 12, 2019 the WIV’s online, public database of samples and virus sequences was taken offline in the middle of the night between 2:00AM and 3:00AM local time. [44] [“Status breakdown of the database of characteristic wild animals carrying virus pathogens (September 2019).” Scientific Database Service Monitoring & Statistics System. https://archive.is/AGtFv#selection-1553.0-1567.2] The database contained more than 22,000 entries consisting of sample and pathogen data collected from bats and mice. The database contained key information about each sample, including what type of animal it was collected from, where it was collected, whether the virus was successfully isolated, the type of virus collected, and its similarity to other known viruses.


Fig. 6: Example Database Entry [45] [“Database of pathogens of bat and murine viruses.” Wikisource, https://zh.wikisource.org/zhhant/% E8%9D%99%E8%9D%A0%E6%BA%90%E5%92%8C%E9%BC%A0%E6%BA%90%E7%97%85%E6%AF%92%E7 %97%85%E5%8E%9F%E6%95%B0%E6%8D%AE%E5%BA%93]

Table 1: Virus data display of bat samples

Data element name / Example

Sample ID / 162387A
Sample tissue type / Anal
Animal type / bat
Source species / Rousettus leschenaultil
Species molecular identificatno / Rousettus sp.
Collection date / 2016-08-21
country / China
province / Yunnan
city / Miaoxin village, Mengna county, Sipsongpanna
GPS information: 101.51944.21.78127
Whether high-throughput sequencing / No
Whether the virus is isolated / No
publishing / Luo Y, Yi B. Jiang RD, et al. Virol. Sin. 2018;33(1):87-95. doi:10.1007/s12250-018-0017-2
Remarks / --
Detection Method / PCR-based
Virus name / Coronaviridae
Test results / Positive
blast result / btcov HKU9
Virus classification / HKU9
Virus sequence / See references for details
Similarity / 9436
Sequence length / 398bp
Sequence-encoded gene / Partial RdRp

To date, there has been no consistent answer provided as to why the database was removed or when or if it will be put back online.

Shi is listed as the data correspondence author for the project. When questioned about the database being taken offline, Shi has given several conflicting answers. During a December 2020 interview with BBC, Shi said the database was taken offline for “security reasons” after cyberattacks against the work and personal emails of WIV staff. She also insisted that WIV virus sequences were saved in the GenBank database, run by the National Center for Biotechnology Information. Shi stated, “It's completely transparent. We have nothing to hide." [46] [Sudworth, John. “Covid: Wuhan Scientist Would 'Welcome' Visit Probing Lab Leak Theory.” BBC News, 21 Dec. 2020, http://www.bbc.com/news/world-asia-china-55364445.]

In a January 26, 2021 email to someone inquiring about the database, however, Shi stated the database was taken down due to cyberattacks “during [the] COVID-19 pandemic.” [47] [Cleary, Tommy. “Prof Zheng-Li Shi Replied to Me, to CNRI,中⽂DOI运维 I Can Only Conclude @PeterDaszak & the Rest of the @WHO Organisation Were given the Same Information Access Ultimatum:No Trust, No Conversation.@SciDiplomacyUSA Has Its Work Cut Out.Data Hostage? Pic.twitter.com/KhiFs42U7j.” Twitter, 10 Mar. 2021, https://twitter.com/tommy_cleary/status ... 25602?s=20.] She also claimed that researchers had “only entered a limit[ed] data in this database” despite it having more than 22,000 entries.

In an apparent contradiction of her BBC interview, Shi admitted that “access to the visitors is limited,” [48] [Sudworth.] but maintains:

…all our work regarding the different type of bat coronavirus (partial sequences or full-length genome sequences) have been published and the sequence and sample information have been submitted to GenBank. [49] [Ibid.]

At the end of her email, Shi writes, “I’ll not answer any of your questions if your curiosity is based on the conspiracy of ‘man made or lab leak of SARS-CoV-2’ or some non-sense questions based on your suspicion. No trust, no conversation” [50] [Ibid.] (emphasis added).

[admin]

Part 2 of 4

New Leadership and PLA Involvement

The WIV’s website indicates that Yuan Zhiming serves as the Dean of the Wuhan Branch of the Chinese Academy of Sciences and director of the WNBL BSL-4 lab. [51] [“Yuan Zhiming.” Wuhan Institute of Virology, http://www.whiov.cas.cn/sourcedb_whiov_ ... 00080.html] However, news posted on Weibo Douban, a PRC website, on February 7th, 2020 stated that PLA officials were dispatched to assume control of the response. The report says PLA Major General Chen Wei, an expert in biology and chemical weapon defenses, was deployed to Wuhan in January 2020 and took control of the WNBL BSL-4 lab. The posting of this information to Douban is significant given the website’s history of censoring posts critical of the CCP, including censoring words related to the Tiananmen Square Massacre. [52] [Gertz, Bill. “Chinese Maj. Gen. Chen Wei TAKES Leading Role in Coronavirus Fight.” The Washington Times, 16 Feb. 2020, http://www.washingtontimes.com/news/202 ... le-in-cor/.] [53] [Guli. “Major General Chen Wei, China's Chief Biochemical Weapons Expert, Takes Over Wuhan P4 Virus Laboratory.” Radio France Internationale, https://www.rfi.fr/cn/%E4%B8%AD%E5%9B%BD/20200208- %E4%B8%AD%E5%9B%BD%E9%A6%96%E5%B8%AD%E7%94%9F%E5%8C%96%E6%AD%A6%E5%99%A8%E 4%B8%93%E5%AE%B6%E9%99%88%E8%96%87%E5%B0%91%E5%B0%86%E6%8E%A5%E7%AE%A1%E6%AD %A6%E6%B1%89p4%E7%97%85%E6%AF%92%E5%AE%9E%E9%AA%8C%E5%AE%A4] [54] [Honorof, Marshall. “China Marks Tiananmen Massacre with 'Internet Maintenance Day.'” NBC News, 4 June 2013, https://www.nbcnews.com/id/wbna52096871] The post’s survival on a heavily CCP censored site confirms its legitimacy.



Committee Minority Staff have also received testimony from a former senior U.S. official that Gen. Chen actually took control of the WNBL BSL-4 lab in late 2019, not January 2020 as was publicly reported. Gen. Chen taking over part of the WIV demonstrates the CCP was concerned about the activity happening there as news of the virus was spreading. If she took control in 2019, it would mean the CCP knew about the virus earlier, and that the outbreak began earlier – a topic discussed further in this section.

Gen. Chen is a researcher at the Academy of Military Medical Sciences in Beijing, and served as a delegate to the 12th National People’s Congress. [55] ["List of Deputies to the Twelfth National People’s Congress of the People’s Republic of China.” Sohu, http://news.sohu.com/20130227/n367313787.shtml] In January 2018, Gen. Chen was made a member of the 13th National Committee of the Chinese People’s Political Consultative Conference (CPPCC). According to the U.S.-China Economic Security Review Commission, the CPPCC is a “critical coordinating body that brings together representatives of China’s other interest groups and is led by a member of China’s highest-level decision-making authority, the CCP’s Politburo Standing Committee.” [56] [Bowe, Alexander. “China’s Overseas United Front Work: Background and Implications for the United States.” U.S.-China Economic and Security Review Commission, 24 Aug. 2018, https://www.uscc.gov/sites/default/file ... inal_0.pdf]

According to a January 15, 2021 fact sheet published by the State Department, in the years leading up to the pandemic, researchers at the WIV were engaged in classified research, including experiments on animals, on behalf of the PLA. [57] [United States, Department of State. “Fact Sheet: Activity at the Wuhan Institute of Virology.” 15 Jan. 2021, https://2017-2021.state.gov/fact-sheet- ... index.html] Dr. Shi has repeatedly denied any involvement of the PLA at the WIV. During a lecture hosted only by Rutgers Medical School, Shi stated:

We—our work, our research is open, and we have a lot of international collaboration. And from my knowledge, all our research work is open, is transparency. So, at the beginning of COVID-19, we heard the rumors that it’s claimed in our laboratory we have some project, blah blah, with army, blah blah, these kinds of rumors. But this is not correct because I am the lab’s director and responsible for research activity. I don’t know any kind of research work performed in this lab. This is incorrect information. [58] [Eban, Katherine. “The Lab-Leak Theory: Inside the Fight to Uncover COVID-19's Origins.” Vanity Fair, 3 June 2021, http://www.vanityfair.com/news/2021/06/ ... 9s-origins.]

This statement is demonstrably false. The WIV had multiple connections to PLA researchers prior to the COVID-19 pandemic; several were listed on the WIV’s English language website. The Academic Committee of State Key Laboratory of Virology at the WIV included a Deputy Director from the Second Military Medical University and a member from the 302 Military Hospital of China. The Scientific Advisory Committee for the Center for Emerging Infectious Diseases had among its members a researcher from the Institute of Military Veterinary at the Academy of Military Medical Sciences. [59] [“Committees.” Wuhan Institute of Virology, https://web.archive.org/web/20200527045 ... ommittees/] This website was scrubbed on May 28, 2020, and the lists of committee members removed. However, archived copies of the website are available online.

Fig. 3: Archived Versions of the WIV Committees Page

Academic Committee of State key laboratory of virology, WIV, CAS

Director:
Zihe RAO, Tsinghua University, China.
Deputy Directors:
Hongyang WANG, The Second Military Medical University, China.
Hongbin SHU, Wuhan University, China.
Members
Jianfang GUI, Institute of Hydrobiology, Chinese Academy of Sciences, China.
Fusheng WANG, 302 Military Hospital of China, China.
Hualan CHEN, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China.
Zhenghong YUAN, Fudan University, China.
Ningshao XIA, Xiamen University, China.
Linqi ZHANG, Tsinghua University, China.
Musheng ZENG, Sun Yat-sen University, China.
Jianguo WU, Wuhan University, China.
Xinwen CHEN, Wuhan Institute of Virology, Chinese Academy of Sciences, China.
Ke LAN, Wuhan University, China.

This raises the obvious question of why Shi, who served on one of the committees, would lie about military researchers working with the WIV. Her denial and the scrubbing of the website appear to be obvious attempts to obfuscate the PLA’s involvement with the WIV.

Geospatial Analysis of Traffic Patterns at Wuhan Hospitals Near the WIV

Around the time the WIV’s virus database went offline, car traffic at hospitals in downtown Wuhan began to increase. Researchers from Boston University School of Public Health, Boston Children’s Hospital, and Harvard Medical School used satellite imagery to examine parking lot volume of hospitals in Wuhan for the two and a half years prior to December 2019. They found that five of six hospitals analyzed had the highest relative daily volume of cars in the parking lot in September and October 2019, before the first reported cases of COVID-19.


Fig. 7: Time-series of Different Influenza-like Illnesses, Symptoms and Surveillance signals [62] [Nsoesie]

This peak corresponded with an increase in searches for “cough” and “diarrhea” in Wuhan on Baidu, a Chinese search engine. [60] [Nsoesie, Elaine Okanyene, et. al. “Analysis of hospital traffic and search engine data in Wuhan China indicates early disease activity in the Fall of 2019 (2020).” Digital Access to Scholarship at Harvard, 2020. http://nrs.harvard.edu/urn-3:HUL.InstRepos:42669767] According to the CDC, both cough and diarrhea are symptoms of COVID- 19. [61] [“Symptoms of COVID-19.” Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-nc ... mstesting/ symptoms.html] This study suggests a virus with similar symptoms as COVID-19 was circulating in Wuhan in September and October.

The Initial Outbreak’s Proximity to the WIV

When people get sick, they are likely to seek healthcare near their home or work. Each of the hospitals that saw a rise in traffic with patients complaining of COVID-19 symptoms are located within 6.5 miles of the WIV Headquarters and are connected by public transit lines. The below map shows the location of the WIV Headquarters (in red) and the six hospitals (in blue) which experienced increase vehicle traffic in September and October 2019. When plotted on a map, these six hospitals are clustered around the WIV Headquarters in Wuchang, Wuhan, and are connected to that facility via the Wuhan Metro – various lines are shown in black, yellow, pink, and green on the map. The pink line represents Line 2, whose daily passenger volume exceeded one million trips in 2017. [63] [“Wuhan Metro is bursting with passengers, breaking records for two consecutive days.” 5 April 2017, https://web.archive.org/web/20170825184 ... 89625.html]


Map 1: Harvard Study Hospitals in Relation to the WIV Headquarters

It is also important to note, according to an Australian scientist who worked in the BSL-4 lab, a daily shuttle bus transfers WIV researchers from the Wuhan Branch of the Chinese Academy of Sciences to the WNBL facility and back again. [64] [Cortez, Michelle Fay. “The Last—And Only—Foreign Scientist in the Wuhan Lab Speaks Out.” Bloomberg, 27 June 2021, http://www.bloomberg.com/news/features/ ... speaks-out.] According to public mapping data, the shuttle pick up and drop off point is less than 500 meters from the WIV Headquarters. As such, it is likely that researchers from both the WIV Headquarters, as well as the WNBL, used the Wuhan metro and/or the WNBL shuttle bus, as part of their daily work commute.

Therefore, it is reasonable to conclude, based on the WIV’s extensive sample library and history of genetically manipulating coronaviruses, that in early September, one or more researchers became infected with SARS-CoV-2 in the lab and carried it out into the city. Based on the WIV’s publications, researchers could have been exposed while experimenting with a natural virus collected from the wild or infected with a virus they genetically manipulated. Those researchers likely traveled to and from the WIV via the Wuhan metro or via the shuttle service, providing a vector for the virus to spread. This corresponds with the first signs of a growing wave of ill people in Wuhan centered around the WIV’s Wuchang facility.

The 2019 Military World Games and Sick Athletes

The 7th International Military Sports Council Military World Games (MWGs) opened in Wuhan on October 18, 2019. The games are similar to the Olympic games but consist of military athletes with some added military disciplines. The MWGs in Wuhan drew 9,308 athletes, representing 109 countries, to compete in 329 events across 27 sports. Twenty-five countries sent delegations of more than 100 athletes, including Russia, Brazil, France, Germany, and Poland. [65] ["Military Games to Open Friday in China.” China Daily, 17 Oct. 2019, http://www.china.org.cn/sports/2019- 10/17/content_75311946.htm.]

The PRC government recruited 236,000 volunteers for the games, which required 90 hotels, three railroad stations, and more than 2,000 drivers. [66] [“2019 Military World Games Kicks off in Central China's Wuhan.” CISION, 17 Oct. 2019, http://www.prnewswire.com/news-releases ... orldgames- kicks-off-in-central-chinas-wuhan-300940464.html.] An archived version of the competition’s website from October 20, 2019, lists the more than thirty venues that hosted events for the MWGs across Wuhan and the broader Hubei province. [67] [“Competition Venues.” Wuhan 2019 Military World Games, https://web.archive.org/web/20191020154 ... on_venues/.] The live website is no longer accessible – it is unclear why it was removed.

During the games, many of the international athletes became sick with what now appear to be symptoms of COVID-19. In one interview, an athlete from Luxembourg described Wuhan as a “ghost town,”[68] [Houston, Michael. “More athletes claim they contracted COVID-19 at Military World Games in Wuhan.” Inside the Games, 17 May 2020, https://www.insidethegames.biz/articles ... s-covid-19] and recalls having his temperature taken upon arriving at the city’s airport. In an interview with The Financial Post, a Canadian newspaper, one member of the Canadian Armed Forces who participated in the games said (emphasis added):

This was a city of 15 million people that was in lockdown. It was strange, but we were told this was to make it easy for the Games’ participants to get around. [I got] very sick 12 days after we arrived, with fever, chills, vomiting, insomnia.… On our flight to come home, 60 Canadian athletes on the flight were put in isolation [at the back of the plane] for the 12-hour flight. We were sick with symptoms ranging from coughs to diarrhea and in between. [69] [Francis, Diane. “Diane Francis: Canadian Forces Have Right to Know If They Got COVID at the 2019 Military World Games in Wuhan.” Financial Post, 25 June 2021, https://financialpost.com/diane-francis ... taryworld- games-in-wuhan.]

The service member also revealed his family members became ill as his symptoms increased, [70] [Ibid.] a development that is consistent with both human-to-human transmission of a viral infection and COVID-19. Similar claims about COVID-19 like symptoms have been made by athletes from Germany, France, Italy, [71] [Houston.] and Sweden. [72] [Liao, George. “Coronavirus May Have Been Spreading since Wuhan Military Games Last October.” Taiwan News, 13 May 2020, http://www.taiwannews.com.tw/en/news/3932712.]

By cross referencing the listed MWG venues with publicly available mapping data, it is possible to visualize the venues (in black) in relation to the WIV Headquarters (in red) and the abovementioned hospitals (in blue). The green figures represent athletes who have publicly expressed their belief they contracted COVID-19 while in Wuhan and are mapped at the venues which hosted the events in which they competed. Some of these athletes resided in the military athletes’ village.

[I got] very sick 12 days after we arrived, with fever, chills, vomiting, insomnia.… On our flight to come home, 60 Canadian athletes on the flight were put in isolation [at the back of the plane] for the 12-hour flight. We were sick with symptoms ranging from coughs to diarrhea and in between.

-- Canadian Athlete

Map 2: WIV Headquarters, Hospitals, MWG Venues, and Sick Athletes

At least four countries who sent delegations to the MWGs have now confirmed the presence of SARS-CoV-2 or COVID-19 cases within their borders in November and December 2019, before the news of an outbreak first became public.

1. Italy. In February 2021, researchers from Italy published a research letter in the CDC’s Emerging Infectious Diseases journal describing a case involving a 4-year-old boy from Milan. A retrospective analysis of samples taken in 2019 identified the boy, who developed a cough on November 21, 2019, as having been infected with SARS-CoV-2 three months before Italy’s first reported case. The boy had no reported travel history. [73] [Amendola, Antonella¸ et. al. “Evidence of SARS-CoV-2 RNA in an Oropharyngeal Swab Specimen, Milan, Italy, Early December 2019.” Emerging Infectious Diseases, Feb. 2021, 27(2). https://doi.org/10.3201/eid2702.204632]

2. Brazil. A March 2021 article by researchers in Brazil examined wastewater samples from October to December 2019. Previous studies have confirmed that humans infected with the virus can experience prolonged viral shedding via their gastrointestinal tract. A sample from November 27th tested positive for SARS-CoV-2 RNA, confirming the virus was circulating in Santa Catarina, Brazil months before January 21, 2020, when the first case in the Americas was reported. [74] [Fongaro, Gislaine et al. “The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil, November 2019.” The Science of the Total Environment, 8 March 2021, 778: 146198. https://dx.doi.org/10.1016%2Fj.scitotenv.2021.146198]

3. Sweden. Sweden’s Public Health Agency said it is likely that individuals in the country were infected with SARS-CoV-2 as early as November 2019. [75] [“Coronavirus May Have Arrived in Sweden in November: Public Health Agency.” The Local, 5 May 2020, http://www.thelocal.se/20200505/the-cor ... -november/.]

4. France. Researchers in France also re-tested samples from late 2019 in an effort to identify early COVID-19 cases. They identified a 42-year-old male who presented to the emergency room on December 27th with an influenza-like illness. He had no connection to the PRC and no recent travel history. Upon re-testing, the patient’s samples were positive for SARS-CoV-2. It should be noted that one of his children also had similar symptoms before the man became sick, suggesting that the first case in France was likely earlier than December 27th. [76] [Deslandes, A et al. “SARS-CoV-2 was already spreading in France in late December 2019.” International Journal of Antimicrobial Agents, 3 May 2020, 55(6): 106006. https://dx.doi.org/10.1016%2Fj.ijantimicag.2020.106006]

As stated above, athletes from France, Italy, and Sweden also complained of illnesses with symptoms similar to COVID-19 while at the MWGs in Wuhan. The presence of SARS-CoV-2 in four countries, on two separate continents, suggests a common source. If, as presumed, SARS-CoV-2 first infected humans in Wuhan before spreading to the rest of the world, the 2019 Military World Games in Wuhan appears to be a key vector in the global spread – in other words, potentially one of the first “super spreader” events.

Conclusion

While much of the public debate was initially focused on the Huanan seafood market in Wuhan as the origin of the pandemic, the preponderance of evidence now suggests that the virus leaked from the Wuhan Institute of Virology. Given the WIV’s demonstrated history of conducting gain-of-function experiments on coronaviruses, including genetically manipulating viruses specifically to make them infectious to humans in BSL-2 labs, as well as their possession of one of the world’s largest collections of coronaviruses, it is completely plausible that one or more researcher(s) was accidentally infected and carried the virus out of the lab. The evidence outlined above, combined the cover-up conducted CCP authorities, strongly suggest the Wuhan Institute of Virology as the source of the current pandemic. [77] [Stahl, Lesley. “What Happened In WUHAN? Why Questions Still Linger on the Origin of the Coronavirus.” CBS News, 28 Mar. 2021, http://www.cbsnews.com/news/covid-19-wu ... 021-03-28/.]

III. EVIDENCE OF GENETIC MODIFICATION

The other topic of debate is whether the virus could have been genetically modified. The WIV was conducting gain-of-function research on coronaviruses and testing them against human immune systems in the months leading up to the emergence of SARS-CoV-2, however the scientific community has claimed it is not possible it was anything but a naturally occurring virus. But, as this report lays out, we believe it is a viable hypothesis that the virus could have been modified.

“You can engineer a virus without leaving any trace. The answers you are looking for, however, can only be found in the archives of the Wuhan laboratory.”

– Dr. Ralph Baric

Research Regarding SARS Like Coronaviruses from 2004-2017

The WIV’s work on bat coronaviruses dates back to the aftermath of SARS in the early 2000s. Shi met Peter Daszak, an American citizen, in 2004 during an effort to find the origins of the 2002 SARS pandemic. Daszak is the CEO of EcoHealth Alliance, a New York-based NGO that funds scientific research around the world. [78] [Zaugg, Julie. “In Wuhan with Bat Woman, at the origins of the Covid-19.” L’Illustre, 22 Jan. 2021, https://www.illustre.ch/magazine/a-wuhanavec- bat-woman-aux-origines-du-covid-19] For the last year and a half, questions have been raised about how and why EcoHealth Alliance provided the WIV with U.S. taxpayer dollars. Those funds were provided to EcoHealth Alliance in the form of grants from the Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Science Foundation (NSF), and the United States Agency for International Development (USAID).



Beginning in 2005, and continuing over the next 16 years, Shi and Daszak have collaborated on coronavirus research. Together, they “led dozens of expeditions to caves full of bats, to collect samples and analyze them.” [79] [Ibid.] They have identified more than 500 novel coronaviruses, including roughly 50 related to SARS or MERS, and they have repeatedly engaged in gain-of-function research on coronaviruses designed to make them more infectious in humans. [80] [Ibid.] As discussed below, the vast majority of the most relevant scientific publications that have emerged from the WIV regarding coronaviruses was conducted with funding provided by Peter Daszak through EcoHealth Alliance.

Article and Publication: “Bats Are Natural Reservoirs of SARS-Like Coronaviruses,” in Science (2005).

Participants: Li Wendog, primary author; Shi, second author and one of three corresponding authors; Peter Daszag; additional scientists from Australia and China.

Funding: The paper was supported in part by funding from the PRC government, who provided a special grant for Animal Reservoirs of SARS-CoV from the State Key Program for Basic Research (grant no. 2005CB523004) and the State High Technology Development Program (grant no. 2005AA219070) from the Ministry of Science and Technology.

It was also funded by the U.S. government, through the NIH and NSF, who provided funding in the form of an ‘Ecology of Infectious Diseases’’ award (no. R01-TW05869) from the John E. Fogarty International Center and the V. Kann Rasmussen Foundation.

Purpose: The scientists hoped to identify the origins of SARS by identifying species of bats which are a natural host for SARS-like coronaviruses.

Conclusion: “These findings on coronaviruses, together with data on henipaviruses (23–25, 28), suggest that genetic diversity exists among zoonotic viruses in bats, increasing the possibility of variants crossing the species barrier and causing outbreaks of disease in human populations. It is therefore essential that we enhance our knowledge and understanding of reservoir host distribution, animal-animal and human-animal interaction (particularly within the wet-market system), and the genetic diversity of bat-borne viruses to prevent future outbreaks.” [81] [Ibid.]

Relevance: This conclusion would drive the next fifteen years of collaboration between the WIV and Peter Daszak, with Shi directing the laboratory work.

In 2006, Shi and Daszak collaborated with a researcher in Australia to publish “Review of bats and SARS” in Emerging Infectious Diseases, a peer-reviewed journal published monthly by the U.S. Centers for Disease Control and Prevention. Shi was again listed as the second author, and the work was funded by the same PRC and NIH/NSF grants referenced above. [82] [Wang L-F, Shi Z, Zhang S, Field H, Daszak P, Eaton BT. “Review of bats and SARS.” Emerg Infect Dis, Dec. 2006; 12(12): 1834-1840., http://dx.doi.org/10.3201/eid1212.060401] The following year, these grants supported the publication of “Evolutionary Relationships between Bat Coronaviruses and Their Hosts” in Emerging Infectious Diseases. Shi is listed as the sixth author, followed by another WIV researcher, and Peter Daszak is listed as one of two corresponding authors. [83] [Cui J, et. al. “Evolutionary relationships between bat coronaviruses and their hosts.” Emerg Infect Dis., Oct. 2007; 13(10):1526-32. https://wwwnc.cdc.gov/eid/article/13/10/07-0448_article]

In 2007, Shi and several other WIV researchers joined additional scientists in publishing another paper on coronaviruses.

Article and Publication: “Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin” in Journal of Virology.

Participants: WIV researchers and Linfa Wang. Shi is listed as the corresponding author.

Funding: This work was funded by the PRC government and grants from Australia and the European Commission.

Purpose: This study focused on the receptors used by the spike protein of SARS-like coronaviruses, which are the major surface structures that enable coronaviruses to bind to receptors on cells. To test this, researchers created multiple chimeric viruses by inserting different sequences of the SARS-CoV spike protein into the spike protein of the SARS-like virus being examined, and tested them against bat, civet, and human ACE2 expressing cells.

Conclusion:

One of these chimeric viruses was able to enter cells through the human ACE2 receptor. ACE2 is an abbreviation for angiotensin converting enzyme-2, which is a protein found on the surface of cells and tissues throughout the human body, including the nose, mouth, and lungs. “In the lungs, ACE2 is highly abundant on type 2 pneumocytes, an important cell type present in chambers within the lung called alveoli, where oxygen is absorbed and waste carbon dioxide is released.” [84] [Sriram, Krishna, et al. “What Is the ACE2 Receptor, How Is It Connected to Coronavirus and Why Might It Be Key to Treating COVID-19? The Experts Explain.” The Conversation, 25 May 2021, https://theconversation.com/what-is-the ... ing-covid- 19-the-experts-explain-136928.] ACE2 is also the location where SARS-CoV-2’s spike protein binds to human cells. Researchers concluded that “a minimal insert region” is “sufficient to convert the SL-COV S [SARS-like coronavirus spike protein] from non- ACE2 binding to human ACE2 binding.” [85] [Ren.]

Relevance: In other words, WIV researchers were able to take a SARS-like coronavirus that does not infect humans and modify it so it was able to do so. Also importantly, this work was done under BSL-2 conditions.

Shi and Daszak do not appear as coauthors on a paper again until 2013.

Article and Publication: “Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor” in Nature. [86] [Ge, Xing-Yi et al. “Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.” Nature, 30 Oct. 2013, 503(7477): 535-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389864/]

Participants: WIV and EcoHealth researchers, including Hu,. Shi, Daszak, and Wang who are credited for designing the experiments. Shi and Daszak listed as corresponding authors.

Funding: The study was funded by grants from the PRC government (including grant no. 2013FY113500), as well as the National Institute of Allergy and Infectious Diseases (NIAID) (no. R01AI079231), a NIH/NSF “Ecology and Evolution of Infectious Diseases” award (no. R01TW005869), an award from the NIH Fogarty International Center supported by International Influenza Funds from the Office of the Secretary of the Department of Health and Human Services (no. R56TW009502), and USAID’s Emerging Pandemic Threats PREDICT program. [87] [Ibid.]

Purpose: This work marked “the first recorded isolation of a live SL-CoV” [88] [Ibid.] [SARS-live coronavirus], which researchers isolated from bat fecal samples and named WIV1. Additionally, they identified two novel bat coronaviruses (SCH014 and Rs3367) and reported “the first identification of a wild-type bat SL-CoV capable of using ACE2 as an entry receptor.” [89] [Ibid.]

Conclusion: “Finally, this study demonstrates the public health importance of pathogen discovery programs targeting wildlife that aim to identify the ‘known unknowns’—previously unknown viral strains closely related to known pathogens. These programs, focused on specific high-risk wildlife groups and hotspots of disease emergence, may be a critical part of future global strategies to predict, prepare for, and prevent pandemic emergence.” [90] [Ibid.]

Relevance: By isolating a wild-type (common strain in nature) SARS-like coronavirus that binds to ACE2, and testing it in human lung tissue, the authors proved that bat coronaviruses are capable of infecting humans directly, without having to pass through an intermediate host.

In 2014, Shi and Daszak coauthored two more joint WIV-EcoHealth Alliance papers. The lead author for one of the papers, entitled “Detection of diverse novel astroviruses from small mammals in China,” was Ben Hu, a WIV researcher who was a coauthor of earlier Shi/Daszak papers. Shi is listed as the corresponding author, and the paper was again jointly funded by the PRC government (including grant no. 2013FY113500) and USAID’s PREDICT program. [91] [Hu, Ben, et. al. “Detection of diverse novel astroviruses from small mammals in China.” J Gen Virol. Nov 2014, 95(Pt 11): 2442-2449. https://pubmed.ncbi.nlm.nih.gov/25034867/]

The next year, in 2015, Shi provided Ralph Baric and other researchers at the University of North Carolina at Chapel Hill with spike protein sequences and plasmids of SCH014, one of the viruses Shi, Daszak, and WIV researchers identified in bat feces samples in 2013. American researchers used those samples to create “a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.” [92] [Menachery, Vineet, et. al. “A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.” Nat Med, 9 Nov. 2015, 21:1508–1513. https://doi.org/10.1038/nm.3985] In other words, they removed the spike protein from SHC014 and inserted it into a SARS coronavirus that was genetically manipulated to better infect mice. This work was done under BSL-3 conditions. The newly created virus was then shown to bind to ACE2 in humans, replicate “efficiently” [93] [Menachery.] in primary human airways cells, and withstand antibodies and vaccines. Researchers concluded that the work “suggests a potential risk of SARSCoV re-emergence from viruses currently circulating in bat populations.” [94] [Ibid.] This research was funded by NIAID and the NIH under multiple awards (nos. U19AI109761, U19AI107810, AI085524, F32AI102561, K99AG049092, DK065988), USAID’s PREDICT program via EcoHealth Alliance, and the PRC government. Baric was the corresponding author. [95] [Ibid.]

2015 also saw the publication of another Shi/Hu/Wang/Daszak paper. Entitled “Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus,” it was published in the Journal of Virology. Nine of the twelve authors were WIV researchers, including Hu and Shi, who was the corresponding author. Here the WIV reported the successful isolation of a second novel coronavirus, WIV16. The SARS-like coronavirus was isolated from a single sample of bat fecal matter collected in Kunming, Yunnan Province of the PRC in July 2013. Like previous papers, this work was supported by a NIAID grant (no. R01AI110964) and by grants from the PRC government (including grant no. 2013FY113500). [96] [Yang, Xing-Lou et al. “Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus.” Journal of Virology, 30 Dec. 2015, 90(6): 3253-6. https://dx.doi.org/10.1128%2FJVI.02582-15]

In addition to her aforementioned work with researchers at UNC Chapel Hill, Shi also provided them with additional bat coronavirus sequences and plasmid of WIV1’s spike protein. The resulting paper, “SARS-like WIV1-CoV poised for human emergence,” was published in the Proceedings of the National Academy of Sciences of the United States of America in March 2016. While neither Shi nor Daszak (nor any WIV researcher) are listed as coauthors, Baric was the corresponding author.

This paper is significant because the authors discuss moving from disease surveillance to creating chimeric viruses as a means of pandemic preparedness; “this manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential.” [97] [Menachery, Vineet, et al. “SARS-like WIV1-CoV poised for human emergence.” Proceedings of the National Academy of Sciences of the United States of America, 14 March 2016, 113(11): 3048-53. https://dx.doi.org/10.1073%2Fpnas.1517719113]

During this work, researchers produced chimeric viruses created by inserting the spike protein from WIV1 into a strain of SARS-CoV adapted to infecting mice. They subsequently tested this chimeric virus in human airway epithelial cells as well as in mice. [98] [Ibid.] In addition to standard BALB/c mice (a strain of albino, lab-breed house mice used in experimentation [99] [“Inbred Strains: BALB.” MGI, http://www.informatics.jax.org/inbred_s ... BALB.shtml.]), researchers genetically manipulated the mice to create a strain of mice expressing the human ACE2 (hACE2) receptor. While hACE2 was found primarily in the lungs of the mice, it was also present in the brain, liver, kidneys, and gastrointestinal tract. The WIV1 chimeric virus was then tested in these hACE2 expressing mice, proving that the chimeric virus could infect humans. This work was funded by NIAID and NIH awards (nos. U19AI109761, U19AI107810, AI1085524, F32AI102561, K99AG049092, DK065988, AI076159, and AI079521). [100] [Menachery 2016.]

In 2016, Shi and Daszak also coauthored two additional papers focused on infectious diseases that year. One, entitled “Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response,” was coauthored by Wang and represents a major step forward in the WIV’s work. While working on this project, WIV researchers created a reverse genetics system and used it to genetically modify WIV1, the live coronavirus that was successfully isolated in 2013 and that UNC researchers manipulated months earlier. WIV researchers created multiple versions of this virus by deleting or adding genetic information to the virus’ RNA. According to the paper, all experiments with live virus for this paper were done under BSL-2 conditions, which does not require respirators or biological safety cabinets. Nine of the eleven authors are WIV researchers, and Shi is the corresponding author. The experimentation for the paper was supported by a grant from NIAID (no. R01AI110964) and funding from the PRC government. [101] [Zeng, Lei-Ping et al. “Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response.” Journal of Virology, 24 June 2016, 90(14): 6573-6582. https://dx.doi.org/10.1128%2FJVI.03079-15]

The following year, Ben Hu was the lead author of a paper entitled “Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.” As with previous papers, the overwhelming majority (14 out of 17) of the authors worked at the WIV. Daszak, Shi, and Wang are all listed as coauthors. Hu is the lead author and Shi is one of two corresponding authors. Daszak is credited for “funding acquisition.” [102] [Hu, Ben et al. “Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.” PLOS Pathogens, 30 Nov. 2017, 13(11). https://dx.doi.org/10.1371%2Fjournal.ppat.1006698]

Additionally, using the reverse genetics system they debuted the previous year, WIV researchers created eight separate chimeric viruses by inserting the spike protein of various SARS-like coronaviruses into WIV1. Two of these chimeric viruses (WIV1-Rs4231S and WIV1-Rs7327S), and one natural virus, Rs4874, all replicated within hACE2 expressing cells. [103] [Hu, 2017.]

To reiterate, WIV researchers created chimeric coronaviruses able to infect humans in 2017, before the WNBL BSL-4 lab became operational. This work was jointly funded by NIAID (no. R01AI110964), USAID’s PREDICT program, and the PRC government (including grant no. 2013FY113500).

Research Regarding SARS-Like Coronaviruses at the WIV or in Conjunction with WIV Scientists from 2018-2019

While Shi and Daszak coauthored several additional papers in 2018 and 2019 regarding coronaviruses, none include gain-of-function research on SARS-like coronaviruses designed to make them more infectious to humans. This is especially odd given that in 2018 the Chinese Academy of Science launched a new special project titled “Pathogen Host Adaption and Immune Intervention.” [104] [“Guidelines for the application of the ‘Pathogen Host Adaptation and Immune Intervention’ project of the Chinese Academy of Sciences Strategic Leading Technology.” Chinese Academy of Sciences, 6 Sept. 2018, https://archive.is/spmNg#selection-3389.0-3389.160] One of the five subprojects was titled “Research on Virus Traceability, Cross-Species Transmission, and Pathogenic Mechanism,” – Shi is listed as one of the two scientists in charge. [105] [Ibid.] This subproject had three areas of focus: 1) the traceability, evolution and transmission mechanism of new pathogens; 2) molecular mechanisms of viral cross-species infection and pathogenicity, and 3) the interaction mechanism between virus and host.

A second WIV scientist, Cui Zongqiang, was one of two researchers in charge of another subproject entitled, “New methods and new technologies for infection and immune research.” [106] [Ibid.] This project focused on, among other things, evaluating new vaccines and establishing “humanized small animal models” [107] [Ibid.] for in vitro pathogen testing. [108] [Ibid.]

In January 2018, Shi was appointed Principal Investigator for a new Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XBD29010101, $1.35 million USD), investigating “genetic evolution and transmission mechanism of important bat-borne viruses.” [109] [Shi, Zheng-li. “Curriculum Vitae.” https://www.ws-virology.org/wp-content/ ... li-Shi.pdf “Study on the evolutionary mechanism of bat SARS-like coronavirus adapted to host receptor molecules and the risk of cross-species infection.”] This project, especially with its focus on transmission mechanisms, aligns with the first focus area mentioned above. That same month, Shi began work on a project titled “Study on the evolutionary mechanism of bat SARS-like coronavirus adapted to host receptor molecules and the risk of crossspecies infection.” [110] [MedSci, https://archive.is/g35C6#selection-1425.0-1425.139] The project was funded at a value of roughly $850,000 USD (grant no. 31770175) and is slated to run until December 2021. [111] [Ibid.] This grant aligns with the second focus area, the description of which specifically mentions replicating and modifying coronaviruses (emphasis added):

For important emerging emergencies and virulent viruses (influenza virus, Ebola virus, coronavirus, Marburg virus, arenavirus, etc.), by studying their ability to invade different host cells and their ability to replicate in different host cells, analyze the key molecules affecting their cross-species infections and their pathogenic mechanisms. Including: virus invasion, virus replication and assembly, and infection model. [112] [“Guidelines for the application of the ‘Pathogen Host Adaptation and Immune Intervention’ project of the Chinese Academy of Sciences Strategic Leading Technology.” Chinese Academy of Sciences, 6 Sept. 2018, https://archive.is/spmNg#selection-3389.0-3389.160]

Shi did not publish any papers funded by this grant before the start of the pandemic. As such, it is impossible to know what experiments she was conducting in the months prior to the pandemic.

Further evidence expands on Shi’s work in 2018 and 2019. In January 2019, Shi and several other scientists were awarded a National Natural Science Award Second Prize for a project entitled, “Research on Important Viruses Carried by Chinese Bats.” [113] [“Catalogue and introduction of the 2018 National Natural Science Award winning projects.” Ministry of Science and Technology, 8 Jan. 2019, https://archive.is/jKq7B#selection-187.0-187.86] Five out of the six researchers on the award were coauthors of the previously discussed 2013 paper entitled, “Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.”

In January 2019, Ben Hu, was awarded $385,850 in grant money (grant no. 31800142) by the Youth Science Fund Project (YSFP) of the National Natural Science Foundation of China. [114] [“Pathogenicity of two new bat SARS-related coronaviruses to transgenic mice expressing human ACE2.” MedSci, https://archive.is/shrM2#selection- 1545.0-1558.0] The YSFP “supports the young researchers to independently select topics within the scope of the scientific funding and carry out basic research.” [115] [“[Good News] 100% winning bid! All applications of the National Natural Science Foundation of China(NSFC) were approved.” Faculty of Economics and Management, ECNU Academy of Statistics and Interdisciplinary Sciences, 11 May 2020, http://asis.ecnu.edu.cn/asisenglish/64/ ... 0/page.htm] This project, selected by Ben Hu, was titled, “Pathogenicity of two new bat SARS-related coronaviruses to transgenic mice expressing human ACE2.” [116] [“Pathogenicity of two new bat SARS-related coronaviruses to transgenic mice expressing human ACE2.” MedSci, https://archive.is/shrM2#selection- 1545.0-1558.0] To date, the two novel SARS-related coronaviruses have not been identified, and the grant money has only been cited in papers published about SARS-CoV-2.

WIV researchers confirmed to the WHO investigative team that they were conducting experimentations testing chimeric coronaviruses in 2018 and 2019. [117] [Joint Report – ANNEXES.] According to an interview with Shi published by Science, all coronavirus experimentation, including infecting hACE2 mice and civets, was done at the BSL-2 and BSL-3 levels – “the coronavirus research in our laboratory is conducted in BSL-2 or BSL-3 laboratories.” [118] [Shi, Zheng-li. “Reply to Science Magazine.” Science Magazine, https://www.sciencemag.org/sites/defaul ... 0Q%26A.pdf]

This ongoing work appears to coincide with Peter Daszak’s stated goal of developing a broadspectrum coronavirus vaccine. In a May 19, 2020, interview with “This Week in Virology,” Daszak discussed the goal of the gain-of-function work he funded on coronaviruses with the WIV (emphasis added):

Coronaviruses are pretty good – I mean you’re a virologist, you know all this stuff – but the… you can... um manipulate them in the lab pretty easily. The spike protein drives a lot of what happens with the coronavirus – zoonotic risk. So, you can get the sequence, you can build the protein, and we work with Ralph Baric at UNC to do this, insert it into a backbone of another virus, and do some work in the lab. So, you can get more predictive when you find a sequence – you’ve got this diversity. Now, the logical progression for vaccines is, if you’re going to develop a vaccine for SARS, people are going to use pandemic SARS, but let’s try to insert some of these other related [viruses] and get a better vaccine. [119] [Racaniello, Vincent. “TWiV 615: Peter Daszak of EcoHealth Alliance.” YouTube, interview by Vincent Racaniello,19 May 2020, https://www.youtube.com/watch?v=IdYDL_RK--w]

Shi, Hu, and others at the WIV were the ones collecting, identifying, genetically modifying, and testing these novel coronaviruses against human immune systems for Peter Daszak.

In sum, in the years leading up to the emergence of SARS-CoV-2, there was:

• Research by Shi and others at the WIV on how to alter the spike protein of non-infectious
SARS-like coronaviruses so that they can bind to human ACE2 receptors;
• Repeated collaboration between Shi, Hu, Daszak, Wang, and other researchers on
genetically manipulating coronaviruses to increase their infectiousness in humans;
• A new PRC Strategic Priority Research Program, run by Shi, that was actively
manufacturing chimeric viruses in BSL-2 and BSL-3 conditions and seeking out novel
viruses;
• Evidence of ongoing collaboration between Shi and the other scientists who first isolated
a live coronavirus in 2013;
• A second grant awarded to Hu to test novel coronaviruses against human immune
systems in BSL-2 and BSL-3 conditions;
• A stated effort to develop a broad-spectrum coronavirus vaccine.

Given the above, it is self-evident that Shi and her colleagues, with funding and support from Daszak, were actively genetically manipulating coronaviruses and testing them against human immune systems in 2018 and 2019, before the beginning of the pandemic.

Unusual Features of SARS-CoV-2

Committee Minority Staff interviews with scientists and current and former U.S. government officials raised several questions about the natural origins of SARS-CoV-2, including:

1. The highly infectious nature of SARS-CoV-2, which they consider as infectious as measles;

2. The lack of an identified intermediate host (found 4 months after the outbreak of SARS and 9 months after MERS); and

3. The highly efficient binding to human ACE2.

The highly contagious nature of SARS-CoV-2 has been a hot topic of conversation since the virus began to spread around the world. Some scientists and other experts point to the incredibly high case numbers as evidence that SARS-CoV-2 is inherently different from known natural betacoronaviruses. For example, MERS first appeared in 2012 and has infected less than 4,000 people. SARS first appeared in 2002 and infected less than 10,000. At the time of writing, less than two years from when it has first appeared, SARS-CoV-2 has infected more than 196.4 million people.

SARS-CoV-2 also has a highly unusual affinity for binding to human ACE2 receptors over other hosts. In February 2020, American researchers examined this issue closely. They found that SARSCoV- 2’s spike protein “binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor.” [120] [Wrapp, Daniel et al. “Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.” Science, 13 March 2020, 367(6483): 1260-1263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164637/] In other words, SARS-CoV-2 binds more than 10 times more tightly to human ACE2 than the virus that causes SARS. The researchers found this likely explains why the virus is so contagious. [121] [Ibid.]

Australian and British researchers also examined how SARS-CoV-2 binds to the ACE2 of various animals, publishing their research in Scientific Reports on June 24, 2021. The scientists found that SARS-CoV-2’s spike protein binds the strongest to human ACE2. They reported (emphasis added):

This finding was surprising as a zoonotic virus typically exhibits the highest affinity initially for its original host species, with lower initial affinity to receptors of new host species until it adapts. As the virus adapts to its new host, mutations are acquired that increase the binding affinity for the new host receptor. Since our binding calculations were based on SARS-CoV-2 samples isolated in China from December 2019, at the very onset of the outbreak, the extremely high affinity of S protein for human ACE2 was unexpected. [122] [Piplani, S., et. al. “In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin.” Scientific Reports, 24 June 2021, 11(13063) https://www.nature.com/articles/s41598-021-92388-5]

The first preprint version of this paper went further, concluding, “the data indicates that SARS-CoV- 2 is uniquely adapted to infect humans, raising important questions as to whether it arose in nature by a rare chance event or whether its origins might lie elsewhere” emphasis added. [123] [Piplani, S., et. al. Preprint of “In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin.” ArXiv, 13 May 2020, https://arxiv.org/abs/2005.06199v1] This research provides evidence that SARS-CoV-2 is uniquely well adapted to humans, suggesting a non-zoonotic source of the outbreak.

The Furin Cleavage Site

One of the most discussed questions centers around the furin cleavage site (FCS) of SARS-CoV-2. The FCS is part of the virus’ spike protein, which enables it to bind to and enter human cells. In February 2020, French and Canadian scientists reported SARS-CoV-2 contains an FCS that is absent in other coronaviruses of the same clade, or branch of viruses believed to have a similar common ancestor. The scientists also reported that when a bronchitis virus was modified by inserting a similar cleavage site, the virus’ pathogenicity was increased. [124] [Coutard, B et al. “The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.” Antiviral Research, Feb. 2020, 176: 104742 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114094/] While some scientists have noted that other coronaviruses contain furin cleavage sites, phylogenetic analysis shows that SARS-CoV-2 is the only identified sarbecovirus (a subsection of betacoronaviruses) with this feature. [125] [Wu, Yiran, and Suwen Zhao. “Furin cleavage sites naturally occur in coronaviruses.” Stem Cell Research, 9 Dec. 2020, 50:102115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836551/]

In January 2021 a group of American researchers published “Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis” in Nature. In the article, researchers reported the FCS “may have facilitated the emergence of SARS-CoV-2 in humans.” [126] [Johnson, B.A., et. al. “Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis.” Nature, 25 Jan. 2021, 591: 293-299. https://www.nature.com/articles/s41586-021-03237-4] Using a reverse genetic system, they created a mutant strain of SARS-CoV-2 which lacked the FCS. The result was a virus that was weakened in human respiratory cells and that exhibited reduced development in hACE2 expressing mice. This demonstrates the importance of the FCS in the rapid spread of COVID-19.

In other words, did the FCS develop naturally, or was it added in via genetic manipulation? Part of the genetic sequence for the FCS includes a CGG double codon (CGG-CGG). This group of six nucleotides (a group of three nucleotides is also known as a codon) is half of the 12 nucleotides that create the FCS. SARS-CoV-2 is the only identified coronavirus within its class to feature this combination. Some believe this is evidence of genetic manipulation, arguing this double codon is a telltale sign of the FCS being artificially inserted into the virus. [127] [Quay, Steven, and Richard Muller. “The Science Suggests a Wuhan Lab Leak.” The Wall Street Journal, 6 June 2021, http://www.wsj.com/articles/the-science ... 1622995184.]

The “No-See-Um” Method

Critics of the theory that the virus was genetically modified or man-made have repeatedly pointed to the apparent lack of telltale signs of genetic manipulation in the SARS-CoV-2 genome. They claim this is “proof” the virus was not only naturally occurring, but that the COVID-19 pandemic could only be the result of a zoonotic spillover event. Such arguments ignore key pieces of evidence to the contrary.

Molecularly cloned viruses were indistinguishable from wild type.

– Dr. Ralph Baric

In 2005, Ralph Baric, one of the researchers at UNC Chapel Hill with whom Shi would later collaborate with between 2014 and 2016, published a paper entitled, “Development of mouse hepatitis virus and SARS-CoV infectious cDNA constructs.” [128] [Baric R.S., Sims A.C. “Development of Mouse Hepatitis Virus and SARS-CoV Infectious cDNA Constructs.” Curr Top Microbiol Immunol, 2005; 287:229-52. https://doi.org/10.1007/3-540-26765-4_8] In this paper, Baric references using a novel genetic engineering system he developed with other UNC colleagues to engineer full-length SARSCoV genomes via a “no-see-um” method. This method allows for the assembly of various partial genomic sequences into a full-length genome, creating a new and infectious coronavirus. [129] [Ibid.] The publication includes the below figure, which is titled, “Systemic Assembly Strategy for the SARS-CoV infectious clone.” It clearly shows the various SARS fragments and how they were used to create a full-length, custom genomic sequence.


Fig. 5: Baric’s “No-See-Um” System

The paper stated these viruses were “indistinguishable from wild type,” [130] [Ibid.] meaning that it is impossible to tell they were synthetically created.

Baric himself confirmed this interpretation in a September 2020 interview, where he stated, “You can engineer a virus without leaving any trace. The answers you are looking for, however, can only be found in the archives of the Wuhan laboratory.” [131] [Renda, Silvia. “Possibile Creare Un Virus in Laboratorio Senza Lasciare Traccia? La Risposta Dell'autore Della Chimera Del 2015 Di Cui Parlò Tg Leonardo.” L'HuffPost, 14 Sept. 2020, http://www.huffingtonpost.it/entry/e-po ... alasciare- traccia-la-risposta-dellesperto_it_5f5f3993c5b62874bc1f7339.] Referring to chimeric viruses he generated in 2015 with WIV researchers, Baric said his team intentionally left signature mutations to show that it was genetically engineered. “Otherwise there is no way to distinguish a natural virus from one made in the laboratory.” [132] [Ibid.]

Shi and Baric have collaborated on multiple papers regarding coronaviruses. The most recent of which was in May 2020, when they joined other researchers in publishing “Pathogenesis of SARSCoV- 2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2.” [133] [Jiang, Ren-Di et al. “Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2.” Cell, 21 May 202, 182(1): 50-58.e8. https://dx.doi.org/10.1016%2Fj.cell.2020.05.027] One year later, Baric signed onto a May 14, 2021, letter published in Science which argued that the lab leak theory must be taken seriously and should be fully evaluated. [134] [Bloom, Jesse D., et. al. “Investigate the origins of COVID-19.” Science, 14 May 2021; 372(6543): 694. https://science.sciencemag.org/content/372/6543/694.1]

In 2017, a dissertation was submitted to the University of Chinese Academy of Sciences by Zeng Leiping, a doctoral student working at the WIV, entitled “Reverse Genetic System of Bat SARS-like Coronaviruses and Function of ORFX.” [135] [Leiping, Zeng. Reverse Genetic System of Bat SARS-like Coronaviruses and Function of ORFX. 2017. The University of Chinese Academy of Sciences, PhD dissertation. English translation first made available by @TheSeeker268 on Twitter, https://twitter.com/TheSeeker268/status ... 07776?s=20] The referenced reverse genetic system is the same that was used by the WIV in 2016 to create genetically modified viruses and conduct experiments with live viruses under BSL-2 conditions. In his dissertation, Zeng stated the he and other WIV researchers used this system to "construct an S gene chimeric recombinant viral infectious BAC clone with WIV1 as the backbone and without leaving any trace sequences (e.g. incorporated enzymatic sites) in the recombinant viral genome” (emphasis added).

In an end-of-chapter discussion in the dissertation, Zeng reiterates this lack of evidence of genetic manipulation, stating:

We established a reverse genetics system for coronaviruses, and based on the genomic backbone of WIV1, we established a scheme to replace the S gene without traces, constructed infectious BAC clones of 12 S-gene chimeric recombinant viruses, and successfully rescued. Four of these recombinant viral strains (including Rs4231, Rs4874, Rs7327, and SHC014) were tested for ACE2 utilization by these strains in humans, civets, and bats.

Zeng was employed at the WIV when he submitted his dissertation, and Shi was his advisor. As such, it is clear that Shi and others at the WIV not only possessed the capability to genetically modify coronaviruses “without traces,” but were actively doing so in the years leading up to the current pandemic. It appears Zeng Leiping is currently a postdoctoral research fellow in bioengineering at Stanford University.

[admin]

Part 3 of 4

IV. EVIDENCE OF A LAB LEAK COVER-UP

In addition to the events previously discussed (sequence database taken offline, road closures during the MWG, etc.), there are several additional incidents that suggest the PRC, WIV researchers, and others were actively working to suppress and discredit early conversations that the virus could have been man-made or that it could have leaked from a WIV facility.

In April 2012, six miners working in a copper mine located in Yunnan province of the PRC fell ill. Between the ages of 30 and 63, the workers presented to a hospital in Kunming with “persistent coughs, fevers, head and chest pains and breathing difficulties.” [139] [Stanway, David. “Explainer: China's Mojiang Mine and Its Role in the Origins of COVID-19.” Reuters, 9 June 2021, http://www.reuters.com/business/healthc ... 021-06-09/.] Three of the six eventually died. Researchers from the WIV were asked to investigate and test samples from the sick miners. They also began collecting samples from bats in the cave that housed the mine, which led to the discovery of several new coronaviruses. As a result, the WIV began a long-term study of the mine, collecting samples each year. Despite this, Shi maintains the miners were killed by a fungus growing on bat feces not from a virus. [140] [Qiu, Jane. “How China's 'Bat Woman' Hunted Down Viruses from SARS to the New Coronavirus.” Scientific American, 1 June 2020, http://www.scientificamerican.com/artic ... onavirus1/]

ID4991 vs. RaTG13: SARS-CoV-2’s “Closest Relative”

A 2016 paper published by PRC researchers (most of whom are affiliated with the WIV) describes these efforts as researchers conducting “surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013.” [141] [Ge, Xing-Yi et al. “Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft.” Virologica Sinica, 3 Feb. 2016; 31(1): 31-40. https://dx.doi.org/10.1007%2Fs12250-016-3713-9] Shi and Hu are listed as coauthors. WIV researchers identified two new betacoronaviruses – HiBtCoV/3740-2 and RaBtCoV/4991. The study concluded, “RaBtCoV/4991 showed more divergence from human SARSCoV than other bat SL-CoVs and could be considered as a new strain of this virus lineage.” [142] [Ibid.] Shi designed and coordinated the study, drafted the manuscript, and is listed as the corresponding author.

Four years later and after the initial reports of an unknown SARS-like coronavirus in Wuhan, Shi and 28 other PRC scientists submitted an article to Nature for publication entitled, “A pneumonia outbreak associated with a new coronavirus of probably bat origin,” [143] [Zhou, P., et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature, 3 Feb 2020, 579: 270–273. https://doi.org/10.1038/s41586-020-2012-7] on January 20, 2020. It was published in early February. It should be noted that this manuscript was submitted on the same day the PRC’s National Health Commission first issued a statement confirming human-to-human transmission – one month after local health officials warned the CCP human-to-human transmissions were occurring. [144] [Wang, Yanan. “Human-to-Human Transmission Confirmed in China Coronavirus.” AP NEWS, 20 Jan. 2020. https://apnews.com/14d7dcffa205d9022fa9ea593bb2a8c5] It is highly unlikely Shi and her coauthors would have written this paper the same day they submitted it, meaning they were aware for days or perhaps weeks that the virus was spreading via from human-to-human transmission and did not alert the world. According to a study by researchers at the University of Southampton, implementing appropriate restrictions based on human-to-human transmission just one week before this paper was published would have reduced the number of cases in Wuhan by 66%. [145] [Lai, Shengjie, et al. “Effect of Non-Pharmaceutical Interventions for Containing the COVID-19 Outbreak in China.” MedRxiv, 2020, https://www.medrxiv.org/content/10.1101 ... 20029843v3.] This would have made a significant difference in the spread of the virus, especially in conjunction with the significant travel that occurred during the Spring Festival, which ran from January 10 to January 23, 2020, when the city of Wuhan was locked down.

Shi is listed as the corresponding author for the article, which states that COVID-19 “has now progressed to be transmitted by human-to-human contact.” [146] [Zhou (2020).] The researchers conclude that RaTG13, an allegedly naturally occurring bat coronavirus, is the closest relative to SARS-CoV-2 (emphasis added):

We then found that a short region of RNA-dependent RNA polymerase (RdRp) from a bat coronavirus (BatCoV RaTG13)—which was previously detected in Rhinolophus affinis from Yunnan province—showed high sequence identity to 2019- nCoV. We carried out full-length sequencing on this RNA sample (GISAID accession number EPI_ISL_402131). Simplot analysis showed that 2019-nCoV was highly similar throughout the genome to RaTG13 (Fig. 1c), with an overall genome sequence identity of 96.2%. Using the aligned genome sequences of 2019-nCoV, RaTG13, SARS-CoV and previously reported bat SARSr-CoVs, no evidence for recombination events was detected in the genome of 2019-nCoV. Phylogenetic analysis of the full-length genome and the gene sequences of RdRp and spike (S) showed that—for all sequences—RaTG13 is the closest relative of 2019-nCoV and they form a distinct lineage from other SARSr- CoVs (Fig. 1d and Extended Data Fig. 2)…The close phylogenetic relationship to RaTG13 provides evidence that 2019-nCoV may have originated in bats. [147] [Ibid.]

A close examination of the paper, and the corrections published months later, reveal inconsistences in the researchers’ claims. Several of the statements made in the above quotation are simply false. After months of criticism and questioning about RaTG13, Shi and the other researchers were forced to publish an addendum on November 17, 2020. That addendum reveals that RaTG13 was actually ID4991, the sample collected years prior in 2012 or 2013, and that the full-length genomic sequence was obtained in 2018, not in January 2020 as the paper originally stated. [148] [Zhou, P., et. al. “Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature, 17 Nov. 2020, 588: E6. https://doi.org/10.1038/s41586-020-2951-z]

Unfortunately, no other labs can confirm the genomic sequence of RaTG13 – Shi said in an interview published in Science Magazine that the entire sample was used up after genomic sequencing. [149] [Shi, Zheng-li. “Reply to Science Magazine.” Science Magazine, https://www.sciencemag.org/sites/defaul ... 0Q%26A.pdf] The inability of outside researchers to verify the genome of RaTG13, and the above efforts to obfuscate when the WIV collected and sequenced RaTG13, raises multiple questions:

• Why leave out of the February 2020 article that the virus sequence was renamed?

• Why lie about when the full-length sequence was obtained?

• Why only issue a correction almost ten months later?

• Why was this sample destroyed via testing when others weren’t?

In December 2020, reporters from BBC News attempted to visit the cave in Yunnan where RaTG13 was collected. They found themselves followed by plain-clothes police officers and stopped at checkpoints where they were told to stay out of the area. [150] [Sudworth, John. “Covid: Wuhan Scientist Would 'Welcome' Visit Probing Lab Leak Theory.” BBC News, 21 Dec. 2020, http://www.bbc.com/news/world-asia-china-55364445.] A French publication, Envoye Special, produced a video in which they reported conversations with villagers who lived near the mine. According to one of those villagers, the mine was closed and monitored via surveillance cameras. That villager also alleged several people were arrested for venturing too close to the mine. [151] [Asis, Francisco de. “Quite Important the Conversation with Danaoshan Inhabitant.- He Pointed towards the Location We Already Knew for the Mine.- The Roadblocks Are Probably the Diverted Traffic We Already Observed Too.Rest of the Story Is Just Incredible! Pic.twitter.com/kzHz7v5rSg.” Twitter, Twitter, 12 Mar. 2021, https://twitter.com/franciscodeasis/sta ... 88641?s=20.]

It is important to note that in March 2020, American, British, and Australian researchers published “The proximal origin of SARS-CoV-2” in Nature Magazine. [152] [Andersen, Kristian G et al. “The proximal origin of SARS-CoV-2.” Nature Medicine, 17 March 2002, 26(4):450-452. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095063/] Regarding RaTG13, they found, “Although RaTG13, sampled from a Rhinolophus affinis bat, is ~96% identical overall to SARSCoV- 2, its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE2.” [153] [Ibid.] “RBD” is an abbreviation for receptor-binding domain, part of the virus’ spike protein. This is the same part of the virus’ genome that Shi, Hu, and other WIV researchers were genetically modifying and replacing as far back as 2015.

If SARS-CoV-2 was genetically modified, this could represent a viable model for how. RaTG13’s RBD, or full spike protein, could be replaced using the WIV’s reverse genetic system. If one of the many unpublished coronaviruses in the WIV’s possession was modified, and the resulting chimeric virus was then exposed to hACE2 expressing mice or civets, the resulting virus could become better adapted to infecting humans – just like SARS-CoV-2.

According to scientists – including those working at the WIV – ID4991/RaTG13 is more closely related to SARS-CoV-2 than any other publicly identified virus. It’s now clear WIV researchers had this virus as early as 2013, several years before the WIV began genetically modifying other coronaviruses found in the wild. Given the largest difference between RaTG13 and SARS-CoV-2 is at the spike protein – precisely where the WIV modified various coronaviruses for years – and that WIV researchers renamed the virus and lied about when they sequenced, ID4991/RaTG13 could be a source of genetic material if SARS-CoV-2 was indeed genetically modified.

According to emails obtained by Buzzfeed News, it appears Kristian G. Andersen, the lead and corresponding author of the abovementioned article, initially considered this a viable theory. In a January 31, 2020 email to Dr. Anthony Fauci, the director of NIAID, Andersen stated that parts of the virus were possibly engineered and inconsistent with evolutionary theory:


Fig. 8: Andersen Email Suggesting SARS-CoV-2 was Genetically Modified [154] [Andersen, Kristian G. Email to Anthony Facui and Jeremy Farrar. 31 Jan. 2020. https://s3.documentcloud.org/documents/ ... emails.pdf]

From: Kristian G. Andersen [DELETE]
Sent: Friday, January 31, 2020 10:32 PM
To: Fauci, Anthony (NIH/NIAID) [E] [DELETE]
Cc: Jeremy Farrar [DELETE]
Subject: Re: FW: Science: Mining coronavirus genomes for clues to the outbreak's origins

Hi Tony,

Thanks for sharing. Yes, I saw this earlier today and both Eddie and myself are actually quoted in it. It's a great article, but the problem is that our phylogenetic analyses aren't able to answer whether the sequences are unusual at individual residues, except if they are completely off. On a phylogenetic tree the virus looks totally normal and the close clustering with bats suggest that bats serve as the reservoir. The unusual features of the virus make up a really small part of the genome (<9,1%) so one has to look really closely at all the sequences to see that some of the features (potentially) look engineered.

We have a good team lined up to look very critically at this, so we should know much more at the end of the weekend. I should mention that after discussions earlier today, Eddie, Bob, Mike, and myself all find the genome inconsistent with expectations from evolutionary theory. But we have to look at this much more closely and there are still further analyses to be done, so those opinions could still change.

Best,
Kristian

The WIV’s intentionally misleading February 2020 paper regarding RaTG13 was uploaded as a preprint on January 23rd. [155] [Zhou, Peng, et. al. Preprint of “Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin.” 23 Jan. 2020, bioRxiv, https://www.biorxiv.org/content/10.1101 ... 2.914952v2] Given that Andersen and his coauthors cited it in their March 2020 paper, it is all but certain that Andersen, Dr. Fauci, and the others would have seen it before Andersen sent this email. The day after Anderson emailed Dr. Fauci on February 1, 2020, Dr. Fauci, Andersen, and others debated this issue via teleconference. Previously, they had agreed to keep the debate confidential. Following this discussion, Andersen abandoned his claims that the virus was genetically modified. [156] [Young, Alison. “'I Remember It Very Well': Dr. Fauci Describes a Secret 2020 Meeting to Talk about COVID Origins.” USA Today, 18 June 2021, http://www.usatoday.com/story/opinion/2 ... 737494002/.] It is unclear what was said on this call that led to Anderson doing so.

Additional Cover-Up Activities by Scientists at the WIV

As more investigative work continues on the type of research being conducted at the WIV, CCP censors and WIV researchers have been deleting or scrubbing references to coronavirus research that could be related to the origins of the COVID-19 pandemic. As previously discussed, Ben Hu received a Youth Science Fund Project award to test the pathogenicity of two novel SARS-related coronaviruses beginning in 2019. In some publicly facing PRC websites, Hu’s name has now been struck from the grant.


Fig. 9: Ben Hu’s Name Removed From 2019 Grant [157] [2019 Natural Science Foundation Query and Analysis System. https://journal.medsci.cn/m/nsfc.do? u=%E4%B8%AD%E5%9B%BD%E7%A7%91%E5%AD%A6%E9%99%A2%E6%AD%A6%E6%B1%89%E7%97%85%E6%AF%9 2%E7%A0%94%E7%A9%B6%E6%89%80]

CO10802 / To study the mechanism of baculovirus Ac34 protein inhibiting the nuclear pathway of mammalian CRM1 / Mu Jingfang / Wuhand Institute of Virology, Chinese Academy of Sciences

C010802 / Pathogenicity of two new bat SARS-related coronaviruses to transgenic mic expressing human ACE2 / -- / Wuhan Institute of Virology, Chinese Academy of Sciences

H1904 / Study on the mechanism of enterovirus 71 type 3A protein antagonizing RNAI antiviral immunity / Qiu Yang / Wuhan Institute of Virology, Chinese Academy of Sciences

Of the almost 80 WIV grants listed in the database, the one awarded to Ben Hu is the only one that does not identify the principal investigator.

A December 12, 2017, interview with Hu was pulled offline after it began circulating on Twitter. In the article, Hu discusses monitoring and collecting samples from the bat cave in Yunnan and his work using the reverse genetic system to insert spike proteins into live coronaviruses. Interestingly, he discusses how Shi Zheng-li “often personally leads the team to take samples.” [158] [“Hunting bat viruses, tracking the origin of SARS, an interview with Dr. Hu Ben, Wuhan Institute of Virology, Chinese Academy of Sciences.” First Author, 12 Dec. 2017, https://archive.vn/sVHmq#selection-45.79-45.215] It is likely that this article was pulled down for drawing attention to the cave where RaTG13 was collected.

Similarly, a 2018 article written by Hu and published on the website for the Wuhan Branch of the Chinese Academy of Sciences has also been removed. [159] [Hu, Ben. “The Wuhan Institute of Virology's "Research on Chinese Bats Carrying Important Viruses" won the first prize of the 2018 Hubei Provincial Natural Science Award.” Wuhan Branch, Chinese Academy of Sciences, 13 April 2018, archived: https://web.archive.org/web/20210107222 ... 91050.html] While the article broadly discusses the work of Shi and other researchers at the WIV, it does not offer any unique insight or evidence of dangerous research. So why was it removed?

Perhaps most incriminating are Shi’s repeated lies about activities taking place at the WIV. In August 2020, after the publication of the Committee Minority Staff’s interim report, the China Global Television Network interviewed Shi about our work. In the resulting article, Shi denied that Major General Chen Wei took over the BSL-4 lab:

Liu Xin: The report actually went further and said that the lab has been taken over by the Chinese military. It says that Major General Chen Wei has succeeded Yuan Zhiming as the Director of the WIV and Chen Wei is a Chinese military medical sciences expert.

Shi Zhengli: This is a rumor; there is no such thing.

Liu Xin: You absolutely deny that the Chinese military has taken over the WIV.

Shi Zhengli: Yes, it is a rumor. [160] [Xin, Liu. “Exclusive Interview: CGTN's Liu Xin Talks to China's 'Bat Woman'.” CGTN, 26 Aug. 2020, https://news.cgtn.com/news/2020-08-22/C ... index.html.]

This is demonstrably false. As previously discussed, posts made on CCP-controlled forums announcing Chen’s arrival acknowledged her takeover of the lab. The report stated, “PLA Maj. Gen. Chen Wei has been in Wuhan for more than 10 days. She took over the P4 lab as if it were a ‘reassurance pill.’” [161] [Guli.]

During the same interview, and in response to Committee Minority Staff raising questions about a possible lab leak, Shi again lied, claiming that all of the WIV’s research has been published and their samples available for review:

Another piece of evidence that I can give you is that our lab has been doing research for 15 years, and all our work has been published. We also have a library of our own genetic sequences, and we have experimental records of all our work related to the virus, which are accessible for people to check. [162] [Xin.]

This, again, is demonstrably false. The WIV’s sequence library was taken offline in September 2019 and is not “accessible for people to check.” Given the previously discussed undisclosed coronavirus research and military activities at the WIV, it is obvious that not “all” of the WIV’s work has been published. Daszak confirmed this in an interview with Nature: “we have data that we’ve gathered over 15 years of working in China — 5 years under a previous grant from the NIH — which haven’t been published yet.” [163] [Subbaraman, Nidhi. “'Heinous!': Coronavirus Researcher Shut down for Wuhan-Lab Link Slams New Funding Restrictions.” Nature News, 21 Aug. 2020, http://www.nature.com/articles/d41586-020-02473-4.]

In a June 2021 interview, Shi told the New York Times, “my lab has never conducted or cooperated in conducting GOF experiments that enhance the virulence of viruses.” [164] [Qin, Amy, and Chris Buckley. “A Top Virologist in China, at Center of a Pandemic Storm, Speaks Out.” The New York Times, 14 June 2021, http://www.nytimes.com/2021/06/14/world ... -leak.html] This is a bizarre claim given the years of published research, often designed and led by Shi, that explicitly sought to make coronaviruses more infectious to humans. In the same interview, Shi lied about WIV researchers falling ill in the fall of 2019 – “The Wuhan Institute of Virology has not come across such cases.” This is despite the State Department’s January 15th 2021 fact sheet and confirmation from a Dutch virologist on the WHO’s investigative team that several researchers were sick. [165] [Gordon, Michael R., et al. “WSJ News Exclusive | Intelligence on Sick Staff at Wuhan Lab Fuels Debate on Covid-19 Origin.” The Wall Street Journal, 23 May 2021, http://www.wsj.com/articles/intelligenc ... 19-origin- 11621796228.]

Cover-Up Activities by the Chinese Communist Party

According to a WHO internal document from August 2020, the PRC put little effort into determining the source of the SARS-CoV-2 after January 2020:

Following extensive discussions with and presentation from Chinese counterparts, it appears that little had been done in terms of epidemiological investigations around Wuhan since January 2020. The data presented orally gave a few more details than what was presented at the emergency committee meetings in January 2020. No PowerPoint presentations were made and no documents were shared. [166] [Kirchgaessner, Stephanie. “China Did 'Little' to Hunt for Covid Origins in Early Months, Says WHO Document.” The Guardian, 23 Feb. 2021, http://www.theguardian.com/world/2021/f ... o-document]

Given the large amount of financial resources devoted by the PRC in the years prior for locating, sampling, identifying, and experimenting with coronaviruses, it is odd that little effort would be put into determining the source of the virus, if the source was unknown. In mid-February 2020, the PRC’s Ministry of Science and Technology issued new guidelines for laboratory research in the PRC. Official PRC sources stressed:

The mention of biosafety at labs by the ministry has nothing to do with some saying that the coronavirus leaked from the Wuhan Institute of Virology of the Chinese Academy of Sciences. [167] [Caiyu, Liu, and Leng Shumei. “Biosafety Guideline Issued to Fix Chronic Management Loopholes at Virus Labs.” Global Times, 16 Feb. 2020, http://www.globaltimes.cn/content/1179747.shtml.]

Experts interviewed in February 2020 by The Global Times stated that PRC labs paid “insufficient attention to biological disposal.” [168] [Ibid.] This included disposing of lab materials into sewage systems. [169] [Ibid.] Given that these new guidelines were issued after the PRC stopped searching for the source of the outbreak, it raises questions as to what prompted the PRC to stop its search.
Shortly thereafter, on February 25, 2020, the Chinese Center for Disease Control and Prevention issued supplementary regulations affecting how PRC scientists work on research related to COVID- 19. The guidelines prohibit researchers from sharing data or samples and requires them to receive permission prior to conducting research or publishing the results.


Fig. 10: Excerpt from China CDC Regulations Issued on February 25th [170] [Chinese Center for Disease Control and Prevention. “On the Supplementary Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus.” 25 Feb. 2020. https://www.documentcloud.org/documents ... -Regs.html]

3. No one can, under their own name or in the name of their research team, provide other institutions and individuals with information related to the COVID-19 epidemic on their own, including data, biological specimens, pathogens, culture, etc.

4. Before publishing papers and research results related to the COVID-19 epidemic, you must first report them to the Science and Technology Group/Department for preliminary review, and if necessary, submit it to the Emergency Leading Group or the Department of Science and Education of the National Health Commission for approval.

Papers that have been submitted but not yet reviewed by the Science and Technology Group/Department should be withdrawn as soon as possible and redone according to these regulations.

A full copy of the regulations is included in the Appendix.

On February 27, 2020, Health Times, published remarks from an interview with Yu Chuanhua, who referenced health data from February 25th. Yu is the Vice President of the Hubei Health Statistics and Information Society and Professor of Epidemiology and Health Statistics at Wuhan University, and was running a database of confirmed COVID-19 cases in early 2020. In the interview, Yu stated he had evidence of COVID-19 cases as early as September 2019:

Professor Yu Chuanhua said, “For example, there is data on a patient who became ill on September 29. The data shows that the patient has not undergone nucleic acid testing. The clinical diagnosis (CT diagnosis) is a suspected case. The patient has died. This data has not been confirmed and there is no time to death. It may also be wrong data." With the research of the database, Professor Yu Chuanhua found more and more case data before December 8. There were two cases in November, and the onset time was November 14 and November 21, 2019. Before December 8, there were also five or six cases. Among them, one patient who became ill at the end of November was hospitalized on December 2 and was clinically diagnosed with pneumonia. [171] [Wang, Zhenya. “Experts Judge the Source of the New Crown: December 8 Last Year May Not Be the Earliest Time of Onset.” Health Times, 27 Feb. 2020, http://www.jksb.com.cn/index.php?m=wap& ... &id=160018.]

Before the interview was published on February 27th, Yu called the reporter and tried to retract the information regarding the two sick patients in November. [172] [Ibid.] It is likely that this was done to comply with the China CDC gag order that was issued two days prior.

Nine days later, on March 5, 2020, the Joint Prevention and Control Mechanism (JPCM) of the State Council Novel Coronavirus Pneumonia Scientific Research Group issued a confidential memo, obtained by the Associated Press, entitled, “Notice on the Standardization of the Management and Publication of Novel Coronavirus Scientific Research.” [173] [Joint Prevention and Control Mechanism of the State Council Novel Coronavirus Pneumonia Scientific Research Group. “Notice on the Standardization of the Management and Publication of Novel Coronavirus Scientific Research.” 3 Mar. 2020. https://www.documentcloud.org/documents ... tions.html] The notice announced the research group was taking control of all publication work related to the pandemic for “coordinated deployment.” [174] [Ibid.] It also required units publishing research to notify the JPCM’s propaganda team, which was tasked to work with a special public opinion team to coordinate publication of research with public opinion and “social concerns.” [175] [Ibid.]


Fig. 11: Excerpt from JPCM Memo

Each member work unit of the scientific research team will gather scientific research information within their own unit and systems, review and check the content and form of its publication, and report it to the scientific research team for approval in a timely manner. The scientific research group's dedicated teams of professionals and various experts are responsible for reviewing the publication's content and format and giving expert opinions, and when necessary, arranging expert assessment. Aft the scientific research group approves, the publishing work unit should, according to work requirements, arrange publication via press conferences, official websites, state social media, news media and other platforms, and notify the propaganda and scientific research teams of the Joint Prevention and Control Mechanism of the State Council. In principle, COVID-19 scientific research should be published first in the form of an official authoritative publication. The special group on public opinion should strengthen communication with the propaganda team, take into account the trend of public opinion and social concerns, and strengthen guidance of the publication of scientific research and information.

The memo concludes with a warning: “Those who fail to apply for approval in accordance with the prescribed procedures and publish unconfirmed false information on scientific research, thereby causing serious adverse social impacts, shall be held accountable.” [176] [Ibid.] A full copy of the memo is included in the Appendix. These documents are clear evidence of the CCP’s effort to restrict research on SARS-CoV-2, so that the only research published supports the Party’s official story on the origins and emergence of COVID-19.

After the release of the Committee Minority Staff’s interim report on the origins of COVID-19, China Global Television Network, a PRC state-owned media outlet, released a propaganda video aimed at undermining this investigation. Entitled, “Clearing up confusion in McCaul report on COVID-19,” the approximately 45-minute video labels the report “misinformation.” [177] [“The Point: Clearing up Confusion in the McCaul Report On Covid-19.” CCTV News, 25 July 2020, https://www.youtube.com/watch? v=n5qYogMTZOw.] It also discusses what they call the “tired old theory that the virus could have leaked from a lab” [178] [Ibid.] and reveals that Shi Zheng-li was interviewed about our report. [179] [Ibid.] The piece also claims the BSL-4 lab space at the WIV was never taken over by Maj. Gen. Chen Wei. [180] [Ibid.] As discussed earlier, this statement is demonstrably untrue.

In June 2021, Jesse Bloom published a preprint entitled, “Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic.” Bloom is a Principal Investigator and Associate Professor for Basic Sciences and the Herbold Computational Biology Program at Fred Hutch, a cancer research center. Bloom was able to recover multiple deleted viral sequences collected from patients in Wuhan in early December 2020. These sequences were originally uploaded to the NIH’s Sequence Read Archive by researchers in Wuhan, but later deleted at their request.

Oddly, these samples more greatly diverge from SARS-CoV-2’s bat coronavirus ancestor – “the earliest SARSCoV-2 sequences were collected in Wuhan in December, but these sequences are more distant from RaTG13 than sequences collected in January from other locations in China or even other countries.” [181] [Bloom, Jesse D. Preprint: “Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic.” bioRxiv, 29 June 2021, https://www.biorxiv.org/content/10.1101 ... 8.449051v2] Bloom concludes (emphasis added):

The fact that this informative data set was deleted suggests implications beyond those gleaned directly from the recovered sequences. Samples from early outpatients in Wuhan are a gold mine for anyone seeking to understand spread of the virus. Even my analysis of 13 partial sequences is revealing, and it clearly would have been more scientifically informative to fully sequence all 34 samples rather than delete the partial sequence data. There is no obvious scientific reason for the deletion: the sequences are concordant with the samples described in Wang et al. (2020a,b), there are no corrections to the paper, the paper states human subjects approval was obtained, and the sequencing shows no evidence of plasmid or sample-to-sample contamination…. Even though the sequencing data were on the Google Cloud (as described above) and the mutations were listed in a table in the Small paper by Wang et al. (2020b), the practical consequence of removing the data from the SRA was that nobody was aware these sequences existed. Particularly in light of the directive that labs destroy early samples (Pingui 2020) and multiple orders requiring approval of publications on COVID-19 (China CDC 2020; Kang et al. 2020a), this suggests a less than wholehearted effort to maximize information about viral sequences from early in the Wuhan epidemic. [182] [Ibid.]

 
The PRC’s efforts to obfuscate the origins of COVID-19 were not limited to destroying samples and silencing doctors, but featured a sustained disinformation campaign as well. As discussed in our previous report, Lijian Zhao, an official within the PRC’s Foreign Ministry, shared an article on Twitter that claimed the virus was brought to the PRC by the U.S. military. [183] [Zhao, Lijian. “This Article Is Very Much Important to Each and Every One of Us. Please Read and Retweet It. COVID-19: Further Evidence That the Virus Originated in the US. Https://T.co/LPanIo40MR.” Twitter, 13 Mar. 2020, http://www.twitter.com/zlj517/status/12 ... 3427906560] The article was from the Global Times research.ca, a website that pushes pro-Putin propaganda and has reported ties to Russian state media. [184] [Thomas, Elise, and Aspi. “Chinese Diplomats and Western Fringe Media Outlets Push the Same Coronavirus Conspiracies.” The Strategist, 30 Mar. 2020, http://www.aspistrategist.org.au/chines ... spiracies/.] His tweet was amplified by the Chinese Embassy in South Africa. [185] [Chinese Embassy in South Africa. “More Evidence Suggests That the Virus Was Not Originated at the Seafood Market in Wuhan at All, Not to Mention the so Called ‘Made in China’. Https://T.co/8cRxkSZB3z.” Twitter, 16 Mar. 2020, http://www.twitter.com/ChineseEmbSA/sta ... 3689587712]


Fig. 12: PRC Spokesman Tweet Suggesting COVID-19 Arrived in Wuhan via the Military World Games

Lijian Zhao @zlj517 Mar 12, 2020
China government official
2/2 CDC was caught on the spot. When did patient zero being in US? How many people are infected? What are the names of the hospitals? It might be US army who brought the epidemic to Wuhan. Be transparent! Make public your data! US owe us an explanation!
1:03
From Global Times
Get the facts about COVID-19

To further drive this narrative, CCP-controlled media outlets accused Maatje Benassi, a member of the U.S. Army Reserve, as being “patient zero.” Benassi competed at the Military World Games without becoming ill, yet has been repeatedly targeted for harassment. Videos pushing the theory have been uploaded to WeChat, Weibo, and Xigua – PRC based sites. Two weeks after Zhao tweeted that the U.S. army brought the virus to Wuhan, the Global Times amplified the narrative, urging the U.S. government to release athletes’ health info and repeated the claim about Benassi. [186] [Shumei, Leng, and Wan Lin. “US Urged to Release Health Info of Military Athletes Who Came to Wuhan in October 2019.” Global Times, 25 Mar. 2020, http://www.globaltimes.cn/content/1183658.shtml.]

Another tweet by Zhao actually suggests the pandemic did start in September, as is suggested in this addendum, but that it began in the United States. [187] [Zhao, Lijian. US CDC Admitted Some #COVID19 Patients Were Misdiagnosed as Flu during 2019 Flu Season. 34 Million Infected & 20000 Died. If #COVID19 Began Last September, & US Has Been Lack of Testing Ability, How Many Would Have Been Infected? US Should Find out When Patient Zero Appeared. Twitter, 22 Mar. 2020, https://twitter.com/zlj517/status/12417 ... 39168?s=20.]


Fig. 13: PRC Spokesman Tweet Suggesting the COVID-19 Pandemic Started in September 2019.

Lijian Zhao @zlj517 Mar 22, 2020
China government official
US CDC admitted some #COVID19 patients were misdiagnosed as flu during 2019 flu season. 34 million infected & 20000 died. If #COVID19 began last September, & US has been lack of testing ability, how many would have been infected? US should find out when patient zero appeared.

It is important to note that this tweet was sent in March 2020. The previously discussed Harvard study suggesting the pandemic began in September was not published until the second half of 2020. This accusation came ten days after Zhao repeated his theory that the U.S. military brought COVID- 19 to Wuhan. If the CCP realized an investigation would show an uptick in visits of patients with symptoms similar to COVID-19 in September, October, and November of 2019, this would likely be the actions they would take to coverup the source of those illnesses.

WIV Disinformation Campaign Involving Peter Daszak

As we have previously explained, Peter Daszak was heavily involved in the gain-of-function research taking place at the WIV, including research that was done at BSL-2 levels and that was done while the United States had a moratorium in place on funding gain-of-function research. In addition, we have uncovered strong evidence that suggests Peter Daszak is the public face of a CCP disinformation campaign designed to suppress public discussion about a potential lab leak. Emails obtained by a third-party organization show that Daszak organized a February 19, 2020, statement in the Lancet “condemn[ing] conspiracy theories suggesting that COVID-19 does not have a natural origin.” [188] [Calisher, Charles et al. “Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19.” Lancet, 7 Mar. 2020, 395(10226): e42-e43. https://pubmed.ncbi.nlm.nih.gov/32087122/] The statement continued, “Conspiracy theories do nothing but create fear, rumours, and prejudice that jeopardise our global collaboration in the fight against this virus.” [189] [Ibid.] The emails show Daszak’s effort to organize a large group of scientists to sign onto a statement that he personally drafted. One email concludes with Daszak stating, “Please note that this statement will not have EcoHealth Alliance logo on it and will not be identifiable as coming from any one organization or person, the idea is to have this as a community supporting our colleagues.” [190] [Daszak, Peter. Email to Linda Saif, Hume Field, JM Hughe, Rita Colweel, Alison Andrew, Aleksei Chmura, Hongying Li, William B. Karesh, and Robert Kessler. 6 Feb. 2020. https://usrtk.org/wp-content/uploads/20 ... 2.6.20.pdf]

The emails, sent from Daszak’s EcoHealth Alliance email account, also reveal the statement was drafted in response to a request by WIV researchers with whom Daszak had worked (emphasis added):

You should know that the conspiracy theorists have been very active, targeting our collaborators with some extremely unpleasant web pages in China, and some have now received death threats to themselves and their families. They have asked for any show of support we can give them. [191] [Daszak, Peter. Email to Rita Colwell. 8 Feb. 2020. https://usrtk.org/wp-content/uploads/20 ... ls_Daszak- 2.8.20.pdf]

In a separate email, Daszak states that Linfa Wang (who did not sign the statement) pushed for Daszak and Baric to not sign the statement, effectively hiding their involvement. As previously discussed, Linfa Wang, who is copied on several other emails about the statement, was a coauthor of multiple Daszak/Shi/Hu papers. Wang is currently the Director and Professor of the Program in Emerging Infectious Diseases at the Duke-NUS Graduate Medical School in Singapore. He is a PRC national who received his B.S. in biochemistry from the East China Normal University in Shanghai, PRC [192] [Wang, Linfa. “Curicullum Vitae.” https://globalhealth.duke.edu/sites/def ... an2017.pdf] before completing a Ph.D. in molecular biology at the University of California, Davis in the United States.

In January 2020, Wang was at the WIV in Wuhan, visiting researchers he worked with. Given his previous publications, this likely included a vsiit with Hu and Shi, with whom he has authored dozens of papers. He departed the city on January 18th, [192] [Kupferschmidt, Kai. “This Biologist Helped Trace SARS to Bats. Now, He's Working to Uncover the Origins of COVID-19.” Science, 9 Sept. 2020, http://www.sciencemag.org/news/2020/09/ ... s-covid-19.] less than three weeks before Daszak externally circulated his draft Lancet statement. Wang is included on the email soliciting cosigners. [193] [Daszak (6 Feb.)]

In the email, Daszak states, (emphasis added):

I spoke with Linfa last night about the statement we sent round. He thinks, and I agree with him, that you, me and him should not sign this statement, so it has some distance from us and therefore doesn't work in a counterproductive way... We'll then put it out in a way that doesn't link it back to our collaboration so we maximize an independent voice. [194] [Daszak, Peter. Email to Ralph Baric, Toni Baric, Alison Andre, and Aleksei Chmura. 6 Feb. 2020. https://usrtk.org/wpcontent/ uploads/2021/02/Baric_Daszak_email.pdf]

Copies of these emails are included in the Appendix.

While pushing for Daszak and Baric, the WIV’s most prominent American collaborators, to hide their efforts to organize this statement, Wang was serving as the Chair of the Scientific Advisory Board for the Center for Emerging Diseases at the Wuhan Institute of Virology, of which Shi Zheng-li is the Director. [195] [Wang.]

Baric agreed and chose not to sign. It is unclear why Daszak ultimately changed his mind and signed the statement. Despite Daszak’s role as the organizer of the Lancet statement, Charles Calisher is listed as the corresponding author. Oddly, the email address listed for Calisher is a generic one ([email protected] [196] [Calisher.]) that appears to have been created specifically for this statement, an unusual practice for scientific publications.

The February 2021 Lancet statement declared the authors had “no competing interest,” despite Daszak organizing the letter on behalf of WIV researchers who he funded and with whom he collaborated. In June 2020, after public concerns regarding Daszak’s connection to the WIV, “the Lancet invited the 27 authors of the letter to re-evaluate their competing interests.” [197] [Editors of The Lancet. “Addendum: competing interests and the origins of SARS-CoV-2.” The Lancet, 26 June 2021, 397: 2449-50. https://www.thelancet.com/action/showPd ... %2901377-5] Daszak submitted a revised disclosure statement which, while transparent about his prior work with PRC researchers, fails to reference the WIV or disclose that he drafted the statement at the request of PRC researchers. [198] [Ibid.]

The emails also reveal that Daszak helped edit a letter sent on February 6, 2020 by the Presidents of the U.S. National Academies of Sciences, Engineering, and Medicine to the White House Office of Science and Technology Policy regarding the origins of COVID-19.

While not included in the final version, the last draft edited by Daszak and the other experts who were consulted included a line stating, “The initial views of the experts is that the available genomic data are consistent with natural evolution and that there is currently no evidence that the virus was engineered to spread more quickly among humans.” Daszak actually pushed for broader language, as he believed “this is a bit too specific, because there are other conspiracy theories out there.” It is unclear why the sentence was removed by the Presidents of the U.S. National Academies before the letter was sent to the White House. Daszak specifically sought to time the publication of his statement in The Lancet for after this letter was released. And the statement references the letter as proof of the virus’ natural origin, without disclosing that Daszak helped edit it. It is highly likely that senior government officials, including Dr. Fauci, would have seen both the letter from the U.S. National Academies of Sciences, Engineering, and Medicine and the statement published in The Lancet, shaping their opinion and stifling debate within the U.S. federal government regarding the origins of COVID-19.

Sixteen months after sending this initial letter, the Presidents of the U.S. National Academies of Sciences, Engineering, and Medicine released an updated statement on June 15, 2021, titled, “Let Scientific Evidence Determine Origin of SARS-CoV-2, Urge Presidents of the National Academies.” [199] [McNutt, Marcia, et al. “NASEM Response to OSTP Re Coronavirus_February 6, 2020.” Received by Kelvin Droegemeier , National Academies of Science, Engineering, and Medicine, 6 Feb. 2020, Washington, District of Columbia. https://www.nationalacademies.org/docum ... 5521A660F4 0FD8D752FFB82A8E21FA8D3C29976D/NASEM%20Response%20to%20OSTP%20re%20Coronavirus_February%206%2C%202020.pdf? hide=thumbs+breadcrumbs+favs+props+nextprev+sidebar+pin+actions&scheme=light&fitwidth] This updated statement acknowledges there are scenarios that the origin of the pandemic could have resulted from a lab leak, stating (emphasis added):

However, misinformation, unsubstantiated claims, and personal attacks on scientists surrounding the different theories of how the virus emerged are unacceptable, and are sowing public confusion and risk undermining the public’s trust in science and scientists, including those still leading efforts to bring the pandemic under control… In the case of SARS-CoV-2, there are multiple scenarios that could, in principle, explain its origin with varying degrees of plausibility based on our current understanding. These scenarios range from natural zoonotic spillover (when a virus spreads from non-human animals to humans) to those that are associated with laboratory work. [200] [Ibid.]

Unlike the letter to the White House, this statement does not state which, if any, outside experts were consulted when drafting the statement.

Interestingly, three weeks later, in July 2021, Daszak and his colleagues released an update to their February 2020 statement with a very similar title: “Science, not speculation, is essential to determine how SARS-CoV-2 reached humans.” The second statement was signed by 24 of the original 27 authors and reflects a major step back from those authors’ original position (emphasis added):

The second intent of our original Correspondence was to express our working view that SARS-CoV-2 most likely originated in nature and not in a laboratory, on the basis of early genetic analysis of the new virus and well-established evidence from previous emerging infectious diseases, including the coronaviruses that cause the common cold as well as the original SARS-CoV and MERS-CoV. Opinions, however, are neither data nor conclusions. Evidence obtained using the scientific method must inform our understanding and be the basis for interpretation of the available information. [201] [Calisher, Charles H et al. “Science, not speculation, is essential to determine how SARS-CoV-2 reached humans.” Lancet, 5 July 2021, 398:209-211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257054/]

This is quite different from Daszak’s words in the first border-line propaganda statement “condemn[ing] conspiracy theories suggesting that COVID-19 does not have a natural origin.” [202] [Calisher (Feb.)] Despite this softening, the authors continue to accuse those who seek to investigate the lab leak hypothesis of being the source of the PRC’s unwillingness to cooperate with an international investigation:

Allegations and conjecture are of no help, as they do not facilitate access to information and objective assessment of the pathway from a bat virus to a human pathogen that might help to prevent a future pandemic. Recrimination has not, and will not, encourage international cooperation and collaboration. [203] [Calisher (July)]

Whereas the first statement cited the letter from the Presidents of the U.S. National Academies of Sciences, Engineering, and Medicine (which Daszak helped edit), the second cites the Presidents’ statement released just weeks prior. This raises the question of whether Daszak, or any of the authors, assisted in drafting or editing the June 15th statement issues by the National Academies.

It should also be noted that Daszak was the only representative of the United States on the WHO-China Joint Study team in early 2021. The United States put forth a list of experts to be considered, none of whom were chosen. Daszak was not on that list but was nevertheless selected and approved by the CCP. [204] [Testimony from former senior U.S. official received by Committee Minority Staff.] The annexes of the WHO’s report on the origins of COVID-19, issued in March 2021, include multiple examples of CCP disinformation that have been repeated by Daszak. This include a discussion of “conspiracy theories,” [205] [Joint Report - ANNEXES.] which include the lab leak hypothesis and questions regarding the possible genetically modified nature of SARS-CoV-2. It also refers to the WIV’s sequence database that was taken offline as a “rumour about missing data.” [206] [Ibid.] This is similar language to that which Daszak used during his Chatham House interview – despite the database remaining offline. [207] [Ibid.] Committee Minority Staff was unable to determine whether Daszak assisted in the drafting or editing of the WHO report.

Peter Daszak has taken several additional concerning actions in regard to the origins of COVID-19, including inexplicably lying about the work conducted by EcoHealth Alliance in the months following the emergence of SARS-CoV-2. In an August 21, 2020, interview with Nature, after the NIH suspended the grants he was using to fund research at the WIV, Daszak claimed “The grant isn’t used to fund work on SARS-CoV-2. Our organization has not actually published any data on SARSCoV- 2.” [208] [Subbaraman.] This is despite the fact that four days later Nature Communications published “Origin and cross-species transmission of bat coronaviruses in China.” [209] [Latinne, Alice et al. “Origin and cross-species transmission of bat coronaviruses in China.” Nature Communications, 25 Aug. 2020, 11(1):4235, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447761/] Daszak, Shi, Hu, and Wang are all listed as authors, with Shi and Daszak both being listed as corresponding authors. The preprint for the article was uploaded on May 31, 2020, almost three months before Daszak’s interview with Nature. The paper includes a phylogenetic analysis “suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.” [210] [Ibid.] Daszak, Shi, three EcoHealth Alliance affiliated researchers, and Linfa Wang are credited with designing the study, conducting fieldwork, and establishing collection and testing protocols.

The research was funded by the NIH (grant no. R01AI110964) and USAID’s PREDICT project (cooperative agreement number GHN-A-OO-09-00010-00), as well as the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB29010101) that Shi was directing. It also received support from the National Natural Science Foundation of China (grants no. 31770175 and 31830096). The paper notes:

All work conducted by EcoHealth Alliance staff after April 24th 2020 was supported by generous funding from The Samuel Freeman Charitable Trust, Pamela Thye, The Wallace Fund, & an Anonymous Donor c/o Schwab Charitable. [211] [Ibid.]

April 24th was the day the NIH terminated the project Understanding the Risk of Bat Coronavirus Emergence, which was funded under grant R01AI110964, [212] [Lauer, Michael. Email to Peter Daszak. 24 April 2020. https://www.sciencemag.org/sites/defaul ... 202020.pdf] which is cited in the paper as funding this work. [213] [Latinne.] The grant Daszak told Nature was not being used to fund work on SARS-CoV-2 is cited in a paper presenting research on SARS-CoV-2.

Earlier, in March 2020, Peter Daszak and two other EcoHealth Alliance affiliated researchers published “A strategy to prevent future epidemics similar to the 2019-nCoV outbreak.” [214] [Daszak, Peter et al. “A strategy to prevent future epidemics similar to the 2019-nCoV outbreak.” Biosafety and Health, March 2020, 2(1): 6-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144510/] While the paper lacked lab experimentation, it discussed SARS-CoV-2 and claimed that “wildlife trade has clearly played a role in the emergence of” [215] [Ibid.] the virus. This work was also funded by the same NIH grant (grant no. R01AI110964), as well as the same cooperative agreement with USAID’s PREDICT Project.

In December 2020, Daszak stated in a tweet that the suspension of the aforementioned NIH grant directly prevented him from accessing samples at the WIV. If the grant did not support EcoHealth Alliance’s work on SARS-CoV-2, how could it be related to their inability to access SARS-CoV-2 samples?

Why did Daszak claim the NIH grant “isn’t used to fund work on SARS-CoV-2” [216] [Subbaraman.] when his own published research and statements show that it was?

Another concerning example of Daszak’s behavior comes from a March 10, 2021 discussion with Chatham House. In response to a question about the WIV taking down its viral sequence and sample database in September 2019 and whether the WHO investigative team requested to see the data, Peter Daszak stated (emphasis added):

I asked the question in front of the whole team, both sides, while we were at the Wuhan Institute of Virology, about the so-called missing database. And what we were told, by Shi Zheng-li, was that there had been hacking attempts on it, about 3,000 hacking attempts, and they took down this excel spreadsheet-based database. Absolutely reasonable. We did not ask to see the data, and as you know, a lot of this work is work that has been conducted with EcoHealth Alliance, and I’m also part of those data, and we do basically know what’s in those databanks. And I shared, I gave a talk to both sides about the work we’ve done with the Wuhan Institute of Virology and explained what’s there. There is no evidence of viruses closer to SARS-CoV-2 than RaTG13 in those databases. It’s as simple as that. [217] [“Sustaining the Response: Inside the WHO-China Mission.” Chatham House, 10 March 2021, https://www.youtube.com/watch? v=GMllEF58944&t=3249s.]

This is a stunning claim given the database contained more than 22,000 samples and was inaccessible by anyone outside of the WIV after September 2019. It was physically impossible for Daszak to remotely access the database after the SARS-CoV-2 genome was released in January 2020 in order to compare the genome to samples in the database. If not, given that no one outside of the WIV knew RaTG13 was closely related to SARS-CoV-2 prior to publication in February 2020, how could Daszak claim to know there is not a closer match in one of the 22,000 plus samples when he could not access the data? This raises the question of whether he has copy of the database.

Daszak has also been, at best, incorrect about how the WIV handed RaTG13. In an April 21, 2020 interview with the New York Times, he stated (emphasis added):

We found the closest relative to the current SARS-CoV-2 in a bat in China in 2013. We sequenced a bit of the genome, and then it went in the freezer; because it didn’t look like SARS, we thought it was at a lower risk of emerging. With the Virome project, we could have sequenced the whole genome, discovered that it binds to human cells and upgraded the risk. And maybe then when we were designing vaccines for SARS, those could have targeted this one too, and we would have had something in the freezer ready to go if it emerged. [218] [Kahn, Jennifer. “How Scientists Could Stop the Next Pandemic Before It Starts.” The New York Times, 21 Apr. 2020, http://www.nytimes.com/2020/04/21/magaz ... ccine.html.]

This is, of course, untrue. Researchers at the WIV fully sequenced RaTG13’s genome in 2018. [219] [Zhou, (Nov. 2020).] Either Daszak knew this was untrue, and lied to the New York Times, or he was being kept in the dark about the work being conducted at the WIV. If the later is true, it raises more questions about Daszak’s March 2021 claim to know everything in the WIV’s database that was taken offline.

[admin]

Part 4 of 4

V. HYPOTHESIS: A LAB LEAK THAT CAUSED A PANDEMIC

Having examined the evidenced discussed in this addendum, Committee Minority Staff has put together the following hypothesis that could reasonably represent what could have occurred in the early months of the COVID-19 pandemic.

In the months leading up to an accidental release of SARS-CoV-2, the hazardous waste treatment system at the WNBL was undergoing renovation. The central air conditioning system at one of the facilities needed to be renovated, which likely resulted in lower than ideal air circulation and enabling viral particles to remain suspended in the air longer. After the July 4, 2019 notice from the Ministry of Science and Technology, and prior to the September 30th deadline, researchers at the WIV were reviewing samples collected under grant 2013FY113500, held by Yuan Zhiming, the Director of the WNBL BSL-4. [220] [“Notice of the Resource Allocation and Management Department of the Basic Research Department of the Ministry of Science and Technology on the Comprehensive Performance Evaluation of Special Projects of Basic Science and Technology Work.” Ministry of Science and Technology, 4 July 2019. https://archive.is/pIwh4#selection-703.7-711.34]

This is the same grant which funded:

• The 2013 paper reporting the first isolation of a live SARS-like coronavirus after sampling at the cave in Kunming. [221] [Ge.]

• The 2014 paper, which was the result of collecting 986 samples from 39 species of small mammals in Guangxi and Yunnan provinces.

• The 2016 paper, where a second live coronavirus was successfully isolated.

• The 2017 paper, where a third live SARS-like coronavirus was isolated and WIV researchers created eight chimeric coronaviruses with altered spike proteins.

Hu, Shi, and others at the WIV were actively testing novel and genetically manipulated coronaviruses against hACE2 expressing mice and civets at BSL-2 and BSL-3 conditions, including viruses collected from the cave in Yunnan where the miners fell ill. A defective hazardous waste treatment system and central air conditioning system would increase the likelihood of a lab employee (or several) becoming infected with SARS-CoV-2, as viral particles would be more likely to remain in the air for longer periods of time. As previously discussed, the WIV provides a shuttle for employees, transporting individuals from near the old WIV facility in Wuchang to the WNBL and back. The infected employees (whether from the WNBL or the WIV Headquarters) then traveled throughout central Wuhan, likely by the metro, spreading the virus.

In early September, it became known that an accidental release occurred. Initially, not knowing SARS-CoV-2 spreads via human-to-human transmission or that asymptotic people are responsible for a large number of new cases, concern was low. Concern was additionally tempered by the knowledge that previous accidental releases from labs resulted in only a small number of infections. Still, measures are ordered in response. At midnight local time on the morning of September 12th, the Wuhan University, which sits less than a mile from the WIV Headquarters and whose medical school houses a BSL-3 lab accredited to experiment on animals, [222] [“About Wuhan University School of Medicine (WUSM).” Wuhan University School of Medicine, 23 Apr. 2013, https://wsm70.whu.edu.cn/English_Site/About.htm] issues a notice for laboratory inspections in late September. [223] [“Notice on the implementation of laboratory safety inspections in 2019.” Wuhan University, http://simlab.whu.edu.cn/info/1107/1018.htm] It is likely that officials issued similar orders to other labs in the area. Between two and three hours later, the WIV’s viral sequence database is taken offline in the middle of the night. [224] [“Status breakdown of the database of characteristic wild animals carrying virus pathogens (September 2019).” Scientific Database Service Monitoring & Statistics System.
https://archive.is/AGtFv#selection-1553.0-1567.2] Roughly 17 hours later, at 7:09 p.m. local time, the WIV publishes a procurement announcement for “security services” at the WNBL, to include gatekeepers, guards, video surveillance, security patrols, and people to handle the “registration and reception of foreign personnel.” [225] [“Competitive consultation on the procurement project of security services in Zhengdian Science Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 12 Sept. 2019, https://web.archive.org/web/20210716170 ... 900712.htm] The budget provided was in excess of $1.2 million. [226] [Ibid.]

In order to prevent national embarrassment, the decision was made to allow the 2019 Military World Games to continue. No spectators were allowed to attend the games, but international athletes and some of the 236,000 volunteers still become infected, spreading the virus in the city. Dozens of athletes fall ill with symptoms. Since COVID-19 can infect humans without causing symptoms, an untold number of athletes and volunteers become infected, but are asymptomatic and unaware they are infectious.

The athletes return to their home countries in late October, carrying SARS-CoV-2 across the world. Just as was the case in 2002 with SARS, [227] [Epstein, Gady A. “Chinese Admit to SARS Mistakes.” Baltimoresun.com, Baltimore Sun, 1 Apr. 2003, http://www.baltimoresun.com/balte. sars21apr21-story.html.] the CCP sought to hide the outbreak, wasting precious time that could have been used to prevent the global pandemic. By the time the world was alerted to the virus spreading in Wuhan, it had already begun to spread around the world.

In December, as cases begin to overload local hospitals, it became impossible to hide the outbreak. At some point in late 2019, Major General Chen Wei is brought in to take over the BSL-4 lab at the WNBL and lead the response efforts. The Wuhan Branch of the China CDC set a case definition for COVID-19 that only included those who have visited the Huanan Seafood Market, meaning that only people who had a link to the market were identified as having COVID-19. This further obscured the true origins of the virus.

Linfa Wang, a scientist with ties to the WIV and who has worked with Shi, Hu, and Daszak on the genetic modification of coronaviruses, was in Wuhan in early January 2020. While there he visited the WIV and likely met with Shi, Hu, and others. Sometime after his departure on January 18th and before February 6th, WIV researchers asked Peter Daszak to organize a public statement suppressing debate regarding the lab as the origin of SARS-CoV-2. On January 20th, WIV researchers submitted the February 2020 article where ID4991 was renamed as RaTG13 and which contained false information about when the genomic sequence for the virus was obtained.

At 12:43am on February 6th, Daszak sent the draft statement to Wang, Baric, and others asking them to join as cosigners. Sometime before Daszak went to bed that night, Wang called him and requested that he, Daszak, and Baric not sign the statement in order to obfuscate their connections to the WIV. Baric agreed, and neither him nor Wang signed the statement. The statement was published on February 19th, declaring discussion of a lab leak a conspiracy theory, and suppressing public debate on the origins of COVID-19.

VI. RECOMMENDATIONS

In the previously issued report, Committee Minority Staff provided several recommendations for actions to be taken by the United States in response to COVID-19, including seeking new leadership at the WHO, pursuing Taiwan’s re-admittance to the WHO as an observer, engaging in an international investigation with likeminded WHO Member States regarding the early stages of COVID-19, and supporting concrete reforms to the International Health Regulations. These recommendations remain relevant.

In response to the new information laid out in this addendum, there are additional steps that can be taken by the Committee, Congress more broadly, and the Executive Branch on this issue. Given the previously detailed inconsistencies and CCP disinformation campaign regarding a possible lab leak, Peter Daszak must be subpoenaed to appear before the House Foreign Affairs Committee and Senate Foreign Relations Committee as material witness to this investigation. Committee Minority Staff attempted, on multiple occasions, to contact Daszak with a list of questions relevant to this report. He never responded. In contrast, Ralph Baric provided answers to a list of questions from Committee Minority Staff. His assistance was appreciated, and we believe his testimony would also be useful. Daszak and Baric should provide expert testimony, including but not limited to the following questions:

• What was the extent of genetic manipulation of coronaviruses and their testing against human immune systems at the WIV in 2018 and 2019?

• Who requested the statement of support published in the Lancet?

• Did this request include labeling discussion of a possible lab leak as a conspiracy theory?

• What was the nature and content of Wang’s call to Daszak in the early hours of February 6th, 2020?

• Why did Daszak make conflicting, and apparently false, statements regarding the NIH grant terminated in 2020?

• How could Daszak confirm RaTG13 is the closet match to SARS-CoV-2 in the WIV’s database if it was taken offline in September 2019?

• Does Daszak have a copy of the WIV’s database that was taken offline?

• Who put forth Daszak’s name to join the joint WHO-China investigative team?

• Was Daszak aware the funding he was providing directly supported gain-of-function research by paying for the collection of viruses the WIV later experimented with, even though the federal government had a moratorium on such research from 2014 through 2017?

• Do they believe SARS-CoV-2 could possibly be a genetically modified virus created via a system similar to Baric’s “no-see-um” method and the system used by WIV researchers in 2016, thus leaving no evidence of manipulation?

Committee Minority Staff also recommends Congress pursue legislation to implement the following restrictions and sanctions in response to the pandemic:

• Institute a ban on conducting and funding any work that includes gain-of-function research until an international and legally binding standard is set, and only where that standard is verifiably being followed.

• Authorize and fund a public-private partnership for pandemic prevention, warning, and early detection.

• Sanction the Chinese Academy of Sciences and affiliated entities.

• List the Wuhan Institute of Virology and its leadership on the Specially Designated Nationals and Blocked Persons List and apply additional, appropriate secondary sanctions.

• Expand statutory and administrative sanctions regimes to curb the abuse of dual-use technology.

• Authorize new sanctions for academic, governmental, and military bioresearch facilities that fail to ensure the appropriate levels of safety and information sharing.

• Review all H-2B visas of Chinese nationals engaged in biological, chemical, or related research in the United States for possible revocation.

• Review all student visas of Chinese nationals studying at U.S. academic institutions for possible revocation.

Additionally, the Executive Branch should engage in international negotiations to establish a legally binding international standard for laboratory biosafety, to include certification and inspections by an international organization similar to the International Atomic Energy Agency.

Foreign governments facing economic contraction that have entered into agreements under the PRC’s Belt and Road Initiative are encouraged to examine bilateral agreement terms. In particular, agreements or memoranda of understanding that promote joint scientific and academic research wherein the Chinese government has access to natural resources, minerals, plant life, and animals unique to the nation state. Agreements that promote adaptation of governing structures that centralize control over all local, municipal, or provincial levels increase the risk of creating national governing structures that manipulate, misinform, misdirect and gaslight their own citizens to protect centralized governing structures.

Foreign governments considering entering into bilateral agreements with the PRC are advised to be aware that based on the information presented within this report, the PRC conducts scientific research without regard for adequate safety protocols in place, in a manner that does not comport with international safety standards, and without adequate assessment of the risks scientific research may pose to the environment, test subjects, or humanity. It is the recommendation of the Committee Minority Staff that such agreements be avoided.

VII. CONCLUSION

The Intelligence Community 90-day review report on the origins of COVID-19, ordered by President Biden, is due no later than August 24, 2021. While based on open source information, it is the hope of Committee Minority Staff that the collection and analysis contained within this addendum, produced at the direction of Ranking Member Michael T. McCaul, will help inform the public debate about the viability of a laboratory accident being the source of SARS-CoV-2. It is vital the public discourse surround the Wuhan Institute of Virology is transparent, honest, and detailed.

It is the opinion of Committee Minority Staff, based on the preponderance of available information; the documented efforts to obfuscate, hide, and destroy evidence; and the lack of physical evidence to the contrary; that SARS-CoV-2 was accidentally released from a Wuhan Institute of Virology laboratory sometime prior to September 12, 2019. The virus, which may be natural in origin or the result of genetic manipulation, was likely collected in the identified cave in Yunnan province, PRC, sometime between 2012 and 2015. Its release was due to poor lab safety standards and practices, exacerbated by dangerous gain-of-function research being conducted at inadequate biosafety levels, including BSL-2. The virus was then spread throughout central Wuhan, likely via the Wuhan Metro, in the weeks prior to the Military World Games. Those games became an international vector, spreading the virus to multiple continents around the world.

It is incumbent on the parties identified in this report to respond to the issues raised herein and provide clarity and any new or additional evidence as soon as possible. As always, Committee Minority Staff stands ready to receive such evidence or testimony that supports or contradicts this report. Until such time as the Chinese Communist Party lifts its self-imposed veil of secrecy, explains its lies regarding the early stages of the pandemic, and provides access to the WIV’s archives and sample database, questions will remain as to the origins of SARS-CoV-2 and the COVID-19 pandemic. Until that day, it is incumbent upon the United States and likeminded countries around the world to ensure accountability, and implement the reforms necessary to prevent the CCP’s malfeasance from giving rise to a third pandemic during the 21st century.

VII. APPENDIX

Timeline of the WIV Lab Leak and the Start of the COVID-19 Pandemic

April 2012: Six miners working in a copper mine located in a cave in Yunnan province of the PRC fall ill. Between the ages of 30 and 63, the workers presented to a hospital in Kunming with persistent coughs, fevers, head and chest pains, and breathing difficulties.” Three of the six died.

Late 2012 – 2015: Researchers from the WIV collect samples from bats in the cave.

2015 - 2017: Shi Zheng-li, Ben Hu, Peter Daszak, and Linfa Wang jointly publish research on the isolation of novel coronaviruses. They conduct gain-on-function research, testing novel and genetically manipulated coronaviruses against mice and other animals expressing human immune systems. At times they collaborate with Ralph Baric.

2018 – 2019: Shi, Hu, and other researchers at the WIV infect transgenic mice and civets expressing human immune systems with unpublished novel and genetically modified coronaviruses.

July 4, 2019: The PRC’s Ministry of Science and Technology orders a review of several grants, including grant no. 2013FY113500. This is the grant which funded the collection of hundreds of coronaviruses and bat samples from the cave in Yunnan province.

July 16, 2019: The WIV publishes a tender requesting bids to conduct renovation on the hazardous waste treatment system at the Wuhan National Biosafety Lab (WNBL). The closing date was July 31st.

Late August/Early September 2019: One or more researchers become accidently infected with SARS-CoV-2, which was either collected in the Yunnan cave, or the result of gain-of-function research at the WIV. They travel by metro in central Wuhan, spreading the virus.

September 12, 2019: At 12:00am local time, the Wuhan University issues a statement announcing lab inspections. Between 2:00am and 3:00am, the WIV’s viral sequence and sample database is taken offline. At 7:09pm, the WIV publishes a tender requesting bids to provide security services at the WNBL.

September – October 2019: Car traffic at hospitals surrounding the WIV Headquarters, as well as the shuttle stop for the WNBL, show a stead increase before hitting its highest levels in 2.5 years. Baidu search terms for COVID-19 related symptoms increase in a corresponding manner.

Late October – Early November 2019: The international athletes return home, carrying SARS-CoV-2 around the world.

November 21, 2019: A 4-year-old boy from Milan, Italy develops a cough. His samples will later test positive for COVID-19.

November 27, 2019: Samples of wastewater are collected in Brazil that will later test positive for the presence of SARS-CoV-2 RNA.

December 1, 2019: The CCP’s first “official” case of COVID-19 become infected.

Late 2019: Major General Chen Wei arrives in Wuhan, taking over the WNBL BSL-4 lab.

Dec. 27, 2019: A Chinese genomic company reportedly sequenced most of the virus in Wuhan and results showed a similarity to SARS. Zhang Jixian, a doctor from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, tells PRC health authorities that a novel disease affecting some 180 patients was caused by a new coronavirus.

Dec. 29, 2019: Wuhan Municipal CDC organized an expert team to investigate after the Hubei Provincial Hospital of Integrated Chinese and Western Medicine and other hospitals find additional cases.

Dec. 30, 2019: Doctors in Wuhan report positive tests for “SARS Coronavirus” to local health officials. Under the 2005 International Health Regulations, the PRC is required to report these results to the WHO within 24 hours. They do not.

Dec. 31, 2019: WHO officials in Geneva become aware of media reports regarding an outbreak in Wuhan and direct the WHO China Country Office to investigate.

Jan. 2020: Linfa Wang meets with collaborators at the WIV, likely including Shi and Hu.

Jan. 1, 2020: Hubei Provincial Health Commission official orders gene sequencing companies and labs who had already determined the novel virus was similar to SARS to stop testing and to destroy existing samples. Dr. Li Wenliang is detained for “rumor mongering.”

Jan. 2, 2020: The Wuhan Institute of Virology (WIV) completes gene sequencing of the virus, but the CCP does not share the sequence or inform the WHO. PRC aggressively highlights the detentions of the Wuhan doctors.

Jan. 3, 2020: China’s National Health Commission ordered institutions not to publish any information related to the “unknown disease” and ordered labs to transfer samples to CCP controlled national institutions or destroy them.

Jan. 11-12, 2020: After a researcher in Shanghai leaks the gene sequence online, the CCP transmits the WIV’s gene sequencing information to the WHO that was completed 10 days earlier. The Shanghai lab where the researcher works is ordered to close.

Jan. 14, 2020: Xi Jinping is warned by a top Chinese health official that a pandemic is occurring.

Jan. 18, 2020: Linfa Wang departs Wuhan.

Jan. 20, 2020: WIV researchers submitted an article claiming that SARS-CoV-2 is natural in origin. The article renames ID4991 as RaTG13 and contained false information about when the genomic sequence for the virus was obtained.

Jan. 23, 2020: The CCP institutes a city-wide lockdown of Wuhan. However, before the lockdown goes into effect, an estimated 5 million people leave the city.

Last Week of January 2020: Daszak and other outside experts edit a letter to be sent by the Presidents of the National Academies of Sciences, Engineering, and Medicine to the White House Office of Science and Technology Policy. Daszak pushes for language to address “conspiracy theories.”

Jan. 30, 2020: One week after declining to do so, Tedros declares a Public Health Emergency of International Concern.

Late Jan. – Early Feb. 2020: PRC researchers, likely those at the WIV, request Peter Daszak’s assistance in responding to suggestions of a lab leak or genetic manipulation of SARS-CoV-2. Daszak helps edit the National Academies of Sciences, Engineering, and Medicine’s response to the White House Office of Science and Technology Policy on the origins of COVID-19.

Feb. 3, 2020: The WIV researchers’ paper submitted on January 20th is published by Nature online.

Feb. 6, 2020 at 12:43:40 am: Daszak sends the draft Lancet statement, which cites the Feb. 3 WIV paper, to Wang, Baric, and others asking them to join as cosigners. Within hours, Wang calls him, informs Daszak that he will not sign, and requests that neither Daszak or Baric sign.

Feb. 6, 2020 (Afternoon): At 3:16pm, Daszak send a High Important email to Baric, forwarding Wang’s request, and informing Baric the statement will be “put out in a way that doesn’t link it back to our collaboration.” At 4:01:22 pm, Baric agrees to not sign the statement.

Feb. 7, 2020: Dr. Li, who first shared the positive SARS test results with his classmates via WeChat, dies from COVID-19.

Feb. 9, 2020: The death toll for COVID-19 surpasses that of SARS.

Feb. 15, 2020: First death from COVID-19 outside of Asia occurs, in France.

Feb. 16, 2020: WHO and PRC officials begin a nine-day “WHO-China Joint Mission on Coronavirus Disease 2019” and travel to the PRC to examine the outbreak and origin of COVID-19. Many team members, including at least one American, were not allowed to visit Wuhan.

Feb. 18, 2020: Daszak statement is published by the Lancet online, which references the letter from the U.S. National Academies of Sciences, Engineering, and Medicine he helped write and the WIV’s February 3rd paper on the origins of COVID-19. Despite drafting the letter, Daszak is not listed as the corresponding author.

Feb. 25, 2020: For the first time, more new cases are reported outside of PRC than within.

Feb. 26, 2020: The WHO-China Joint Mission issues its findings, praising the PRC for its handling of the outbreak.

Feb. 29, 2020: The first reported COVID-19 death in the United States occurs.

March 11, 2020: The WHO officially declares the COVID-19 outbreak a pandemic after 114 countries had already reported 118,000 cases including more than 1,000 in the United States.

Nov. 17, 2020: As a result of public pressure, Shi, Hu, and other WIV researchers publish an addendum to their February 3rd paper, confirming that RaTG13 was ID4991 collected from the cave in Yunnan, and revealing they collected 293 coronaviruses from the cave between 2012 and 2015.

June 15, 2021: The Presidents of the U.S. National Academies of Sciences, Engineering, and Medicine release a statement saying, “let scientific evidence determine origin of SARS-CoV-2.”

June 21, 2021: After public pressure, Daszak updates his public disclosure form for the Lancet statement. He does not mention the WIV or that the statement was drafted at the request of PRC researchers.

July 5, 2021: Daszak and 23 of the original 27 authors release an update to their February 2021 statement, walking back their labeling of public debate around the source of the virus as “conspiracy theories.”

**********









Memo to the Offices of the Chinese Center for Disease Control and Prevention

Memo (2020) No. 16 of the Science and Technology Department

On the Supplementary Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus Pneumonia

All units and offices directly under the center:

In order to further strengthen scientific research management in our center during the emergency response to the novel coronavirus pneumonia, and in accordance with the spirit of relevant documents issued by the higher authorities, the "Supplementary Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus Pneumonia" has been formulated. Every unit and office, please attach great importance to it and spread it through all levels -- everyone must be notified. In case of any violation of relevant regulations, the offender and their unit will be held accountable.

Attachment: Supplementary Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus Pneumonia

Chinese Center for Disease Control and Prevention
February 25, 2020

cc: Gao Fu, Li Xinhua, Liu Jianjun, Feng Zijian.



Annex: Supplementary Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus Pneumonia

According to the spirit of the "Notice of the General Office of the National Health Commission on Strengthening the Management of Biological Sample Resources and Related Scientific Research Activities during the Prevention and Control of Major Infectious Diseases" (National Health Commission Science and Technology Memo [2020] No. 3), the "Notice of the General Office of the Ministry of Science and Technology on Strengthening the Management of New Coronavirus Pneumonia Science and Technology Research Projects" and other documents, and in order to effectively combat the new coronavirus pneumonia ("COVID-19") epidemic, to strictly standardize scientific research management, and to further strengthen the implementation of scientific research management systems, these supplementary "Regulations on Strengthening the Management of Science and Technology During the Emergency Response to the Novel Coronavirus Pneumonia" (Chinese Center for Disease Control Science and Technology Memo [2020] No. 128) have been formulated.

1. Prioritize the interests of the country and the people and take the prevention and control of the COVID-19 epidemic as the primary task. During the emergency response against the epidemic, we must concentrate our forces, distinguish our priorities, focus our main energies on controlling the epidemic, write papers "on the land of the motherland", apply research results to the fight against the epidemic, and not focus on publishing papers until the epidemic is under control.

2. The launch of scientific research projects related to the COVID-19 epidemic must undergo preliminary review by the Science and Technology Group/Department. According to the research subject, experts should be organized to conduct scientific and ethical reviews, and, if necessary, the project must be submitted to the emergency leading group or the Department of Science and Education of the National Health Commission for approval. The research projects authorized by higher authorities must be examined and approved by the emergency leading group via the Science and Technology Group/Department and be kept on record.



3. No one can, under their own name or in the name of their research team, provide other institutions and individuals with information related to the COVID-19 epidemic on their own, including data, biological specimens, pathogens, culture, etc.

4. Before publishing papers and research results related to the COVID-19 epidemic, you must first report them to the Science and Technology Group/Department for preliminary review, and if necessary, submit it to the Emergency Leading Group or the Department of Science and Education of the National Health Commission for approval.

Papers that have been submitted but not yet reviewed by the Science and Technology Group/Department should be withdrawn as soon as possible and redone according to these regulations.

5. In principle, progress reports on scientific research projects should be reported to the Science and Technology Group/Department on a monthly basis, or according to the time period stipulated by higher authorities.

6. Strictly follow relevant regulations on medical ethics, scientific research integrity and academic spirit.

7. Anyone who violates the above regulations shall be dealt with severely in accordance with discipline, laws and regulations.

8. The date of the implementation of this regulation will be explained by the Science and Technology Group/Department.

Chinese Center for Disease Control and Prevention
February 25, 2020

**********









Joint Prevention and Control Mechanism of the State Council in Response to the Novel Coronavirus Pneumonia Scientific Research Group

Notice on the Standardization of the Management of Publication of Novel Coronavirus Pneumonia Scientific Research

To the Joint Prevention and Control Mechanism of the State Council in Response to the Novel Coronavirus Pneumonia member work units and offices, and other relevant work units:

In order to thoroughly implement relevant requirements from the meeting of the Joint Prevention and Control Mechanism of the State Council in Response to the Novel Coronavirus Pneumonia (hereinafter referred to as the "Joint Prevention and Control Mechanism of the State Council"), and to effectively standardize the management of the publication of scientific research, the following is issued below.

1. Comprehensively strengthen the management of publication of scientific research

In accordance with the principles of "following laws and regulations, being scientific and objective, centralized management, and precise publications", all publication work on epidemic prevention research and information related to COVID-19, including medication, vaccines, virus origins, virus transmission routes, testing reagents, etc. will be taken over by the Joint Prevention and Control Mechanism of the State Council's scientific research group (hereinafter referred to as "the scientific research group") for coordinated deployment. The scientific research group will coordinate the publication of information on emergency scientific research by all work units in all locations.



2. Establish a standardized publication mechanism for scientific research

Each member work unit of the scientific research team will gather scientific research information within their own unit and systems, review and check the content and form of its publication, and report it to the scientific research team for approval in a timely manner. The scientific research group's dedicated teams of professionals and various experts are responsible for reviewing the publication's content and format and giving expert opinions, and when necessary, arranging expert assessment. Aft the scientific research group approves, the publishing work unit should, according to work requirements, arrange publication via press conferences, official websites, state social media, news media and other platforms, and notify the propaganda and scientific research teams of the Joint Prevention and Control Mechanism of the State Council. In principle, COVID-19 scientific research should be published first in the form of an official authoritative publication. The special group on public opinion should strengthen communication with the propaganda team, take into account the trend of public opinion and social concerns, and strengthen guidance of the publication of scientific research and information.

3. Strictly require all scientific research units to do a good job on the publication of scientific research

The member work units of the scientific research team of the Joint Prevention and Control Mechanism shall follow the principle of centralized management, strictly enforce their own system's publication approval procedures for relevant scientific research, strengthen the management of universities, research institutions, and enterprises under the centralized management of their work unit systems, and communicate the requirements of this notice to all relevant units engaged in research on COVID-19. The publishing work unit is the one primarily responsible for the research content they publish, and they must consider, in a comprehensive manner, the research progress, the epidemic prevention and control situation, societal concerns, the consequences of publication, and various other issues. They must ensure the accuracy of the published content and guide societal expectations in a reasonable manner. During the period of epidemic prevention and control, all universities, research institutions, medical institutions, enterprises and their staff shall not publish information on scientific research related to epidemic prevention and control without approval. Papers exchanged on the Chinese Medical Association ...

**********



http://rapeutation.com/acovidsarslableak2z6.jpg

February 6, 2020, Email at 12:43 am from Peter Daszak to Ralph Baric, Linfa Wang, and Others Inviting Them to Sign the Statement

A Statement in support of the scientists, public health and medical professionals of China

Feb. 6, 2020 12:43:40 AM EST

A Statement in support of the scientists, public health and medical professionals of China

Subject: A Statement in support of the scientists, public health and medical professionals of China
From: Peter Daszak [DELETE]
To: Ralph Baric [DELETE]
Cc: [DELETE]
Sent: February 6, 2020 12:43:40 AM EST
Attachments: Statement of support, 2019nCoV China Final.docx

**********



A Statement in support of the scientists, public health and medical professionals of China

Feb. 6, 2020 12:43:40 AM EST

Dear Ralph, Linda, Jim, Rita, Linfa and Hume,

I’ve been following the events around the novel coronavirus emergence in China very closely and have been dismayed by the recent spreading of rumors, misinformation and conspiracy theories on its origins. These are now specifically targeting scientists with whom we’ve collaborated for many years, and who have been working heroically to fight this outbreak and share data with unprecedented speed, openness and transparency. These conspiracy theories threaten to undermine the very global collaborations that we need to deal with a disease that has already spread across continents.

We have drafted a simple statement of solidarity and support for scientists, public health and medical professionals of China, and would like to invite you to join us as the first signatories. If you agree, we will send this letter to a group of around half-a-dozen other leaders in the field and then disseminate this widely with a sign-up webpage for others to show their support by signing up to its language. I will then personally present this at my plenary during the ICID 2020 conference in Malaysia in two weeks, with the goal of also getting widespread attention in SE Asia to our support for the work that our colleagues in China are undertaking.

I sincerely hope you can join us. Please review the letter, and let me know if you are willing to join Billy Karesh and myself as co-signatories. Also, please confirm your title and affiliation that will be shown in the letter. We plan to make circulate this widely to coincide with a letter from the Presidents of the US National Academies of Science, Engineering, and Medicine, which will likely be released tomorrow or Friday.

Thank you for your consideration and support of the scientific and public health community around the world!

Cheers,

Peter

Peter Daszak
President
EcoHealth Alliance
460 West 34th Street – 17th Floor
New York, NY 10001
Tel. +1 212-380-4474
Website: http://www.ecohealthalliance.org
Twitter: @PeterDaszak

EcoHealth Alliance leads cutting-edge research into the critical connections between human and wildlife health and delicate ecosystems. With this science we develop solutions that prevent pandemics and promote conservation.

**********



A Statement in support of the scientists, public health and medical professionals of China

Feb 6, 2020 12:43:40 AM EST

Statement in Support of the Scientists, Public Health, and Medical Professionals of China Combating the Novel Coronavirus Outbreak

We, the undersigned, are scientists who have followed the emergence of 2019-nCoV, and are deeply concerned about its global impact on people’s health and well-being. We have watched as the scientists, public health and medical professionals of China have worked heroically to rapidly identify the pathogen behind this outbreak, put in place significant measures to reduce its impact, and share their results transparently with the global health community. We sign this statement in solidarity with all scientists, public health, and medical professionals in China who continue to save lives and protect global health during the challenge of this novel coronavirus outbreak. We want you to know that we are all in this together, with you in front of us on the battlefield against the novel coronavirus.

The rapid, open and transparent sharing of data on 2019-nCoV is now being threatened by rumors and misinformation around the origins of this outbreak. We stand together to strongly condemn conspiracy theories suggesting that 2019-nCoV does not have a natural origin. Scientific evidence overwhelmingly suggests that this virus originated in wildlife, as have so many other emerging diseases (1-4). This is further supported by a letter from the Presidents of the US National Academies of Science, Engineering, and Medicine, and by the scientific communities they represent (INSERT REF). Conspiracy theories will do nothing but create fear, rumors, and prejudice that jeopardize our global collaboration in the fight against this virus. We need to prioritize scientific evidence and unity over misinformation and conjecture now. We want you all to know that we stand with you, the science and health professionals of China, in your fight against this virus.

We invite others to join us in supporting the scientists, public health, and medical professionals of Wuhan and across China. Stand with our colleagues on the front-line!

Please add your name in an act of support by going to [INSERT LINK HERE].



A Statement in support of the scientists, public health and medical professionals of China

Feb 6, 2020 12:43:40 AM EST

Signatories

Dr. Peter Daszak, President, EcoHealth Alliance
Dr. Jim Hughes, Professor Emeritus, Emory University
Dr. Rita Colwell, former Director of National Science Foundation
Dr. Ralph Baric, Professor, The University of North Carolina, Chapel Hill
Dr. Linda Saif, Distinguished University Professor, The Ohio State University
Dr. Billy Karesh, Executive Vice President, EcoHealth Alliance
Dr. Linfa Wang, Professor, Duke-NUS Medical School
Dr. Hume Field, Honorary Professor, The University of Queensland

References

1. P. Zhou et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, (2020).

2. R. Lu et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, (2020).

3. N. Zhu et al., A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, (2020).

4. L. Ren et al., Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J. Epub ahead of print, (2020).

**********



February 6, 2020, Email at 3:16pm from Peter Daszak to Ralph Baric Relaying Wang's Request Not to Sign the Statement

To: Peter Daszak [DELETE]
Cc: [DELETE]
From: Baric, Ralph [DELETE]
Sent: Thur 2/6/2020 4:01:22 PM (UTC-05:00)
Subject: RE: No need for you to sign the "Statement" Ralph!

I also think this is a good decision. Otherwise it looks self-serving and we lost impact. ralph

From: Peter Daszak [DELETE]
Sent: Thursday, February 6, 2020 3:16 PM
To: Baric, Ralph S. [DELETE]
Cc: [DELETE]
Subject: No need for you to sign the "Statement" Ralph!!
Importance: High

I spoke with Linfa last night about the statement we sent round. He thinks, and I agree with him, that you, me and him should not sign this statement, so it has some distance from us and therefore doesn't work in a counterproductive way.

Jim Hughes, Linda Saif, Hume Field, and I believe Rita Colwell will sign it, then I'll send it round some other key people tonight. We'll then put it out in a way that doesn't link it back to our collaboration so we maximize an independent voice.

Cheers,

Peter

Peter Daszak
President
EcoHealth Alliance
460 West 34th Street – 17th Floor
New York, NY 10001
Tel. +1 212-380-4474
Website: http://www.ecohealthalliance.org
Twitter: @PeterDaszak

EcoHealth Alliance leads cutting-edge research into the critical connections between human and wildlife health and delicate ecosystems. With this science we develop solutions that prevent pandemics and promote conservation.

**********



February 8, 2020, Email at 8:52pm from Peter Daszak to Rita Colwell Alleging WIV Researchers Requested the Statement

From: Peter Daszak [DELETE]
Sent: Saturday, February 08, 2020 8:52 PM
To: Rita Colwell [DELETE]
Cc: Rita Colwell [DELETE]
Subject: RE: coronavirus statement
Importance: High

Hi Rita,

I appreciate your comments and I think at this point, that work has already been done, with >50 genomes published from 12 countries, and phylogenetic analyses published by authors from multiple countries. I’ve tried to make this a bit more clear, and have edited the letter as follows, so it hopefully addresses your comments:

1) I’ve inserted a reference to the GISAID webpage where 57 (to date) full genome sequences of 2019-nCoV from 12 countries are published and analyzed

2) I’ve inserted a reference to the CDC webpage on 2019-nCoV which makes the following statement, completely in concurrence with our letter:

"2019-nCoV is a betacoronavirus, like MERS and SARs, both of which have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir."

In addition, please note that we will not be referring to this as a ‘petition’ but as a ‘statement in support of’ – This is in the title and will be in all materials we send out. This is to avoid the appearance of a political statement – this is simply a letter from leading scientists in support of other scientists and health professionals who are under serious pressure right now.

I hope you are willing to sign on to this -- your voice will be very influential, particularly in keeping these critical bridges open between the USA and China. You should know that the conspiracy theorists have been very active, targeting our collaborators with some extremely unpleasant web pages in China, and some have now received death threats to themselves and their families. They have asked for any show of support we can give them. As soon as we hear back from you we’ll get ready to send this to our larger list (attached), but of course if you don’t feel comfortable, I’ll make sure your name is not associated with this.

Cheers,

Peter

Peter Daszak
President
EcoHealth Alliance
460 West 34th Street – 17th Floor
New York, NY 10001

[admin]

Genetic susceptibility for COVID-19–associated sudden cardiac death in African Americans
by John R. Giudicessi, MD, PhD,∗† Dan M. Roden, MD,‡§‖ Arthur A.M. Wilde, MD, PhD,¶# and Michael J. Ackerman, MD, PhD†∗∗††∗
ncbi.hlm.nih.gov
Heart Rhythm. 2020 Sep; 17(9): 1487–1492.
Published online 2020 May 5. doi: 10.1016/j.hrthm.2020.04.045
PMCID: PMC7198426

John R. Giudicessi
∗Clinician-Investigator Training Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
†Division of Heart Rhythm Services, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota

Dan M. Roden
‡Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
§Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee
‖Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee

Arthur A.M. Wilde
¶Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
#European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart)

Michael J. Ackerman
†Division of Heart Rhythm Services, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
∗∗Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
††Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota

"In 2000 Dutch researchers, for instance, earned the gratitude of rodents everywhere by genetically engineering the spike protein of a mouse coronavirus so that it would attack only cats."

-- The origin of COVID: Did people or nature open Pandora’s box at Wuhan?, by Nicholas Wade

HIGHLIGHTS:

African Americans account for 26% of confirmed COVID-19 cases but 43% of COVID-19 deaths....COVID-19 mortality rates in predominantly black counties are 6-fold higher than that in predominantly white counties....

Current evidence supports the notion that the common ion channel variants p.Asp85Asn-KCNE1 and p.Ser1103Tyr-SCN5A confer an increased risk of DI-LQTS and DI-SCD (Table 1 ).13 Importantly, p.Ser1103Tyr-SCN5A is seen almost exclusively in individuals of African descent and its frequency in that population (∼8%) is higher than that of p.Asp85Asn-KCNE1 (0.2%–2.5% depending on ancestry; 0.2% in individuals of African origin)...

Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death.

-- SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr, by Stacy AS Killen, Jennifer Kunic, Lily Wang, Adele Lewis, Bruce P Levy, Michael J Ackerman & Alfred L George Jr.

In individuals of African descent, the common SCN5A-encoded Nav1.5 sodium channel variant p.Ser1103Tyr-SCN5A has been associated with an increased risk of VA/SCD.14 , 15 , 17 Of note, this proarrhythmic potential has been reported to be enhanced by nongenetic risk factors known to reduce cardiac repolarization reserve (eg, hypokalemia and QTc-prolonging medication exposure....p.Ser1103Tyr-SCN5A is overrepresented in African American sudden infant death syndrome decedents...p.Ser1103Tyr-SCN5A confers an increased risk of sudden death in African Americans regardless of age....

Direct and/or indirect myocardial injury/stress, as assessed by cardiac biomarkers such as troponin I and brain-type natriuretic peptide, has emerged as both a prominent and a prognostic feature in COVID-19. Of note, in an adjusted Cox regression model, the mortality risk associated with elevated cardiac biomarkers/acute cardiac injury was more significant than age and high-risk comorbid conditions such as chronic obstructive/fibrotic pulmonary disease, diabetes, and a history of cardiovascular disease....

p.Ser1103Tyr-SCN5A could produce a similar African American–specific susceptibility to hypoxia-induced VA/SCD in the setting of SARS-CoV-2 infection/COVID-19....

Unfortunately, the increased risk of VA/SCD linked to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant is likely not limited to the possibility of hypoxia-induced VA/SCD. As succinctly outlined in recent work by Lazzerini et al,27 the exaggerated immune response triggered by SARS-CoV-2 infection, specifically elevation of IL-6, likely increases arrhythmia risk via (1) modulation of cardiac ion channel expression/function leading to APD prolongation (eg, direct IL-6–mediated blockade of hERG/Kv11.1 potassium channels), (2) cardiac sympathetic nervous system hyperactivity, and (3) inhibition of cytochrome P450 enzymes involved in the metabolism of some QTc-prolonging drugs (eg, IL-6 and CYP3A4) (Figure 1). The latter effect of IL-6 is particularly important given that a number of COVID-19 pharmacotherapies (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir) under investigation and/or in use clinically are known to prolong the QTc interval and predispose to DI-TdP/DI-SCD ...

these data suggest that 1 in 13 African Americans may be at a substantially increased risk of potentially lethal VAs, most notably DI-TdP, during the COVID-19 pandemic because of the perfect storm of (1) intrinsic genetic susceptibility (i.e., p.Ser1103Tyr-SCN5A), (2) modifiable environmental risk factors (eg, electrolyte abnormalities and concurrent QTc-prolonging drug use), and (3) COVID-19–specific risk factors (eg, profound hypoxemia and cytokine storm) (Figure 1). Whether population-specific genetic risk factors such as p.Ser1103Tyr-SCN5A are contributing to the spike in sudden deaths and racial health disparities observed in COVID-19 epicenters remains to be proven, and given the lack of banked DNA in these epicenters, this speculation may not even be testable.

Nevertheless, given the potential for COVID-19 to exacerbate known gene-environment interactions pertaining to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant, it seems reasonable (1) to avoid using COVID-19–directed QTc-prolonging drugs (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir)...

A potentially pro-arrhythmic common variant, p.Ser1103Tyr-SCN5A, present in 1 out of 13 individuals of African descent has the potential to increase the risk of drug- and hypoxia-induced ventricular arrhythmias/sudden cardiac death and contribute to observed racial health disparities in the COVID-19 pandemic. As such, the use of unproven, QTc-prolonging COVID-19-directed therapies, most notably the combination of hydroxychloroquine and azithromycin, should be limited.

-- Genetic susceptibility for COVID-19–associated sudden cardiac death in African Americans
by John R. Giudicessi, MD, PhD, Dan M. Roden, MD, Arthur A.M. Wilde, MD, PhD, and Michael J. Ackerman, MD, PhD

Introduction

Since emerging from Wuhan, China, in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has infected >3.2 million individuals worldwide and ∼1 million in the United States (as of April 29, 2020).1 , 2 Despite the institution of measures designed to “flatten the curve,” COVID-19 has claimed the lives of >225,000 individuals worldwide and >60,000 individuals in the United States alone (as of April 29, 2020).2 Of note, mortality estimates in some of the hardest hit regions have already or may need to be revised to account for a spike in sudden deaths occurring at home.3 , 4

Although most of these deaths are likely directly attributable to COVID-19 (eg, pulseless electrical activity/respiratory arrests), many of the same regions within the United States have also seen the outpatient prescription volume of COVID-19–directed heart rate–corrected QT interval (QTc)–prolonging drug(s), specifically hydroxychloroquine, rise by as much as 22,700% compared to the same time period (March 15–31) in 2019.5 Importantly, recent studies have shown that between 11% and 25% of hospitalized patients with COVID-19 treated with chloroquine or hydroxychloroquine and azithromycin had QTc values rise above the critical 500 ms threshold.6 , 7

As a result, a substantial number of patients with COVID-19, prescribed these so-called corona cocktails, may be at an increased risk of developing drug-induced long QT syndrome (DI-LQTS), which could deteriorate into drug-induced torsades de pointes (DI-TdP) or worse drug-induced sudden cardiac death (DI-SCD).8 , 9 Therefore, it stands to reason that the same phenomenon (DI-LQTS/DI-TdP) that has already halted 1 chloroquine/hydroxychloroquine clinical trial7 and led the Food and Drug Administration to caution against the use of chloroquine/hydroxychloroquine outside the hospital setting/clinical trial10 could also be contributing, at least in small part, to the increase in sudden deaths observed in some COVID-19 epicenters.

In addition, the COVID-19 pandemic has already highlighted alarming health disparities in the United States. For example, in Illinois where age, sex, and racial demographic data are reported for all COVID-19 cases, African Americans account for 26% of confirmed COVID-19 cases but 43% of COVID-19 deaths.11 A similar trend has been observed across the United States where COVID-19 mortality rates in predominantly black counties are 6-fold higher than that in predominantly white counties.12 Although this phenomenon is likely explained by the convergence of multiple cultural and socioeconomic factors,12 an underlying genetic susceptibility to SARS-CoV-2 infection, its sequelae (such as hypoxia and inflammation), or the potentially lethal side effects of COVID-19–directed therapies (ie, DI-TdP and DI-SCD), assuming equal exposure to these medications, could also contribute.

Current evidence supports the notion that the common ion channel variants p.Asp85Asn-KCNE1 and p.Ser1103Tyr-SCN5A confer an increased risk of DI-LQTS and DI-SCD (Table 1 ).13 Importantly, p.Ser1103Tyr-SCN5A is seen almost exclusively in individuals of African descent and its frequency in that population (∼8%) is higher than that of p.Asp85Asn-KCNE1 (0.2%–2.5% depending on ancestry; 0.2% in individuals of African origin) (Table 1).13 Furthermore, unlike p.Asp85Asn-KCNE1 whose proarrhythmic potential is largely limited to DI-LQTS risk, the modest increase in late/persistent sodium current generated by p.Ser1103Tyr-SCN5A is accentuated markedly by hypoxia/acidosis and has been linked to an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in African Americans across the age spectrum.13, 14, 15, 16

Table 1

Epidemiological and functional data supporting a role for p.Ser1103Tyr-SCN5A and p.Asp85Asn-KCNE1 in DI-LQTS risk

Gene / dbSNP ID / Amino acid change / Overall MAF (gnomAD) / African MAF (gnomAD) / Asian MAF (gnomAD) / European MAF (gnomAD)∗ / Latino MAF (gnomAD) / Electrophysiological phenotype (in vitro) / Odds ratio (95% confidence interval) / References

SCN5A / rs7626962 / S1103Y† / 0.008 / 0.08 / 0.00003 / 0.0003 / 0.004 / Increased sustained/late INa secondary to altered inactivation gating that is accentuated by intracellular acidosis / 8.7 (3.2–23.9) / 16, 17

KCNE1 / rs1805128 / D85N / 0.009 / 0.002 / 0.003 / 0.01 / 0.003 / Decreased IKs and/or IKr secondary to altered activation/inactivation kinetics / 9.0 (3.5–22.9) / 33

dbSNP = Single Nucleotide Polymorphism Database; DI-LQTS = drug-induced long QT syndrome; gnomAD = Genome Aggregation Consortium; IKs = slowly activating delayed rectifier potassium current; IKr = rapidly activating delayed rectifier potassium current; INa = sodium current; MAF = minor allele frequency.

Adapted from Giudicessi et al,13 with permission. Copyright © Lippincott, Williams and Wilkins, 2018.

∗Includes individuals of both Finnish and non-Finnish European ancestry.

†Based on the reference transcript used. p.Ser1103Tyr-SCN5A is also occasionally listed as p.Ser1102Tyr-SCN5A.

Given the potential of p.Ser1103Tyr-SCN5A to exacerbate outcome-related health disparities in the COVID-19 pandemic, this review was assembled to raise awareness of the multiple mechanism(s) whereby the proarrhythmic p.Ser1103Tyr-SCN5A common variant may increase the risk of VA/SCD in those of African descent as well as the importance of identifying modifiable risk factors for mortality during the COVID-19 pandemic.

Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death.

-- SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr, by Stacy AS Killen, Jennifer Kunic, Lily Wang, Adele Lewis, Bruce P Levy, Michael J Ackerman & Alfred L George Jr.

p.Ser1103Tyr-SCN5A and VA/SCD susceptibility in individuals of African descent

In individuals of African descent, the common SCN5A-encoded Nav1.5 sodium channel variant p.Ser1103Tyr-SCN5A has been associated with an increased risk of VA/SCD.14 , 15 , 17 Of note, this proarrhythmic potential has been reported to be enhanced by nongenetic risk factors known to reduce cardiac repolarization reserve (eg, hypokalemia and QTc-prolonging medication exposure; odds ratio 8.7; 95% confidence interval 3.2–23.9; P = .00003)17 and/or structural heart disease (relative risk 8.4; 95% confidence interval 2.1–28.6; P = .001) (Table 1).14 , 15 Furthermore, p.Ser1103Tyr-SCN5A was associated with potentiation of the QT-prolonging effect of hypokalemia in the 4476 participants of the Jackson Heart Study, suggesting that p.Ser1103Tyr-SCN5A contributes to decreased cardiac repolarization reserve at a population-specific level.18 In addition, 2 population-based studies reported that p.Ser1103Tyr-SCN5A is overrepresented in African American sudden infant death syndrome decedents,16 , 19 providing additional epidemiological evidence that p.Ser1103Tyr-SCN5A confers an increased risk of sudden death in African Americans regardless of age.

Besides this epidemiological evidence, in vitro functional characterization by 2 independent groups demonstrated that p.Ser1103Tyr-SCN5A alters the inactivation gating of the Nav1.5 sodium channel (negative shift in the voltage dependence of steady-state inactivation [V1/2]) and accentuates the sustained/late sodium current that is also the signature of the electrophysiological phenotype displayed by the type 3 long QT syndrome (LQT3) pathogenic variants.16 , 17 , 20 That said, the experimental conditions—physiological pH vs low intracellular pH—under which p.Ser1103Tyr-SCN5A increased the late sodium current differed in the studies of Splawski et al17 and Plant et al,16 respectively. Furthermore, neither study demonstrated an in vitro or in silico ability of p.Ser1103Tyr-SCN5A to prolong the action potential duration (APD) in the absence of a “second hit” such as blockade of the rapid component of the delayed rectifier potassium current or intracellular acidosis. This appears to be consistent with (1) the exaggerated QTc response to hypokalemia observed in p.Ser1103Tyr-SCN5A–positive participants of the Jackson Heart Study18 and (2) a circumstance-dependent proarrhythmic state in infants (respiratory acidosis caused by hypoxia/apnea)16 , 19 and older (DI-LQTS in the setting of ≥1 QTc-prolonging drug and advanced structural heart disease) p.Ser1103Tyr-SCN5A–positive African Americans.14, 15, 16

Implications of p.Ser1103Tyr-SCN5A during the COVID-19 pandemic

Direct and/or indirect myocardial injury/stress, as assessed by cardiac biomarkers such as troponin I and brain-type natriuretic peptide, has emerged as both a prominent and a prognostic feature in COVID-19.21, 22, 23 Of note, in an adjusted Cox regression model, the mortality risk associated with elevated cardiac biomarkers/acute cardiac injury was more significant than age and high-risk comorbid conditions such as chronic obstructive/fibrotic pulmonary disease, diabetes, and a history of cardiovascular disease.23 , 24 In addition, life-threatening VAs (eg, ventricular tachycardia/ventricular fibrillation) have been documented in ∼6% of hospitalized patients with COVID-19 and appear to be driven by underlying myocardial injury.25

The proposed mechanisms of acute myocardial injury and resulting VA risk in patients with COVID-19 include (1) direct SARS-CoV-2 myocardial infection (eg, myocarditis), (2) myocardial stress induced by hypoxemic respiratory failure, and/or (3) an exaggerated immune response that results in high levels of circulating cytokines (ie, interleukin-6 [IL-6], tumor necrosis factor-α, etc) directly injuring cardiomyocytes (Figure 1 ).25, 26, 27 Notably, IL-6 may prolong the ventricular action potential via modulation of cardiac ion channel expression/function.27


Figure 1. Potential gene-environment interactions leading to an increased risk of ventricular arrhythmias and sudden cardiac death in p.Ser1103Tyr-SCN5A–positive patients with COVID-19. APD = action potential duration; CHF = congestive heart failure; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; COVID-19 = coronavirus disease 2019; IL-6 = interleukin-6; INa = sodium current; QTc = heart rate–corrected QT; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SCD = sudden cardiac death; SSRI = selective serotonin reuptake inhibitor; VA = ventricular arrhythmia.

Under normal physiological circumstances, Nav1.5 cardiac sodium channels conduct a tiny amount of persistent/late sodium current that contributes minimally to the maintenance of the action potential plateau (ie ≤0.5% of the peak sodium current [INa]).28 However, in the setting of hypoxia, myocardial ischemia, heart failure, and LQT3-causative SCN5A gain-of-function variants, the relative contribution of the late sodium current can increase up to 10-fold to 4%–5% of the peak INa.16 , 20 , 28 , 29 In turn, this “pathological” late sodium current can prolong ventricular APD and predispose to VA/SCD.

As discussed previously, p.Ser1103Tyr-SCN5A Nav1.5 sodium channels function normally under physiological conditions (eg, intracellular pH of 6.9–7.1).16 However, when intracellular pH is decreased in vitro to levels consistent with respiratory acidosis that occurs secondary to hypoxia/prolonged apnea (eg, intracellular pH of 6.6–6.8), p.Ser1103Tyr-SCN5A Nav1.5 sodium channels generate a proarrhythmic, LQT3-like increase in persistent/late sodium current (∼5% of the peak INa).16 This mechanism was put forward initially to explain the gene-environment interaction(s) responsible for the association between p.Ser1103Tyr-SCN5A and sudden infant death syndrome.16 However, the profound hypoxia observed in many COVID-19 cases raises reasonable concern that p.Ser1103Tyr-SCN5A could produce a similar African American–specific susceptibility to hypoxia-induced VA/SCD in the setting of SARS-CoV-2 infection/COVID-19 (Figure 1).

Unfortunately, the increased risk of VA/SCD linked to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant is likely not limited to the possibility of hypoxia-induced VA/SCD. As succinctly outlined in recent work by Lazzerini et al,27 the exaggerated immune response triggered by SARS-CoV-2 infection, specifically elevation of IL-6, likely increases arrhythmia risk via (1) modulation of cardiac ion channel expression/function leading to APD prolongation (eg, direct IL-6–mediated blockade of hERG/Kv11.1 potassium channels), (2) cardiac sympathetic nervous system hyperactivity, and (3) inhibition of cytochrome P450 enzymes involved in the metabolism of some QTc-prolonging drugs (eg, IL-6 and CYP3A4) (Figure 1). The latter effect of IL-6 is particularly important given that a number of COVID-19 pharmacotherapies (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir) under investigation and/or in use clinically are known to prolong the QTc interval and predispose to DI-TdP/DI-SCD (Table 2 ).8 , 30

Table 2

COVID-19–directed pharmacotherapies with DI-TdP/DI-SCD risk

Possible COVID-19 therapy / In vitro inhibition of SARS-CoV-2 / CredibleMeds classification / VT/VF/TdP/LQTS in FAERS∗ / Cardiac arrest in FAERS∗ / References

Repurposed antimalarial agents: Chloroquine / Yes / Known TdP risk / 72 / 54 / 34, 35, 36

Hydroxychloroquine / Yes / Known TdP risk / 222 / 105 / 37,38

Repurposed antiviral agents; Lopinavir/ritonavir / Unknown† / Possible TdP risk / 27 / 48 / 39, 40, 41

Adjunct agents: Azithromycin / Unknown / Known TdP risk / 396 / 251 / 42,43

COVID-19 = coronavirus disease 2019; DI-SCD = drug-induced sudden cardiac death; DI-TdP = drug-induced torsades de pointes; FAERS = Food and Drug Administration Adverse Event Reporting System; LQTS = long QT syndrome; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TdP = torsades de pointes; VF = ventricular fibrillation; VT = ventricular tachycardia.

Adapted from Giudicessi et al,8 with permission. Copyright © Elsevier, 2020.

∗Adverse event reporting from postmarketing surveillance does not account for prescription volume and is often subjected to significant bias from confounding variables, quality of reported data, duplication, and underreporting of events.

†Lopinavir/ritonavir inhibits other SARS viruses in vitro. However, a recent randomized trial demonstrated no benefit in COVID-19.

Taken together, these data suggest that 1 in 13 African Americans may be at a substantially increased risk of potentially lethal VAs, most notably DI-TdP, during the COVID-19 pandemic because of the perfect storm of (1) intrinsic genetic susceptibility (ie, p.Ser1103Tyr-SCN5A), (2) modifiable environmental risk factors (eg, electrolyte abnormalities and concurrent QTc-prolonging drug use), and (3) COVID-19–specific risk factors (eg, profound hypoxemia and cytokine storm) (Figure 1). Whether population-specific genetic risk factors such as p.Ser1103Tyr-SCN5A are contributing to the spike in sudden deaths and racial health disparities observed in COVID-19 epicenters remains to be proven, and given the lack of banked DNA in these epicenters, this speculation may not even be testable.

Nevertheless, given the potential for COVID-19 to exacerbate known gene-environment interactions pertaining to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant, it seems reasonable (1) to avoid using COVID-19–directed QTc-prolonging drugs (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir) unless careful, and preferably personal protective equipment–sparing, cardiac monitoring can be implemented (Figure 2 )8 , 31; (2) to explore the association between p.Ser1103Tyr-SCN5A and rates of sudden death and COVID-19–related mortality in areas with medical record–linked DNA biobanks (eg, UK Biobank); (3) to investigate further the feasibility of point-of-care p.Ser1103Tyr-SCN5A genetic testing; and (4) to determine the clinical utility of QTc-shortening agents such as late sodium current blockers (eg, mexiletine and lidocaine) and anti-IL-6–targeted therapies (eg, tocilizumab and sarilumab)27 , 32 to better protect at-risk individuals, especially African Americans in the context of the ongoing COVID-19 pandemic.


Figure 2. Proposed approach to mitigating the risk of DI-TdP/DI-SCD in patients with COVID-19 treated with ≥1 QTc-prolonging drug. The estimated 99th percentile QTc values, derived from otherwise healthy individuals, that place a patient in the “green light” category are <460 ms before puberty, <470 ms in men, and <480 ms in women. We estimate that the baseline QTc assessment will place 90% in the “green light,” 9% in the “yellow light,” and 1% in the “red light” category. No randomized controlled trial data are available to support the clinical efficacy of any of the COVID-19–directed QTc-prolonging drugs despite the Food and Drug Administration’s Emergency Use Approval of hydroxychloroquine. COVID-19 = coronavirus disease 19; CV = cardiovascular; DI-SCD = drug-induced sudden cardiac death; DI-TdP = drug-induced torsades de pointes; ECG = electrocardiogram; QTc = heart rate–corrected QT; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TdP = torsades de pointes. Adapted from Giudicessi et al,8 with permission. Copyright © Elsevier, 2020.

Conclusion

A potentially pro-arrhythmic common variant, p.Ser1103Tyr-SCN5A, present in 1 out of 13 individuals of African descent has the potential to increase the risk of drug- and hypoxia-induced ventricular arrhythmias/sudden cardiac death and contribute to observed racial health disparities in the COVID-19 pandemic. As such, the use of unproven, QTc-prolonging COVID-19-directed therapies, most notably the combination of hydroxychloroquine and azithromycin, should be limited to settings where careful cardiac monitoring can be implemented (e.g. hospital setting or clinical trial).

Footnotes

This work was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.

Dr Ackerman is a consultant for Abbott, Audentes Therapeutics, Boston Scientific, Invitae, LQT Therapeutics, Medtronic, MyoKardia, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor. However, AliveCor was not involved in this study. The rest of the authors report no conflicts of interest.

References

1. Huang C., Wang Y., Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. [PMC free article] [PubMed] [Google Scholar]
2. Dong E., Du H., Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20:533–534. [PMC free article] [PubMed] [Google Scholar]
3. Deaths from cardiac arrests have surged in New York City. The Economist. https://www.economist.com/graphic-detai ... -york-city Published April 13, 2020. Accessed April 29, 2020.
4. Katz J., Lu D., Sanger-Katz M.U.S. coronavirus death toll is far higher than reported, C.D.C. data suggests. The New York Times. https://www.nytimes.com/interactive/202 ... total.html Published April 28, 2020. Accessed April 29, 2020.
5. Williams M. Hydroxychloroquine prescription volume changes during COVID-19. Swoop Web site. https://www.swoop.com/news/hydroxychlor ... g-covid-19
6. Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin [published online ahead of print April 24, 2020]. Nat Med. 10.1016/j.hrthm.2020.05.014. [PubMed] [CrossRef]
7. Borba M.G.S., Val F.F.A., Sampaio V.S. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open. 2020;3 [PubMed] [Google Scholar]
8. Giudicessi J.R., Noseworthy P.A., Friedman P.A., Ackerman M.J. Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19) Mayo Clin Proc. 2020;95:1213–1221. [PMC free article] [PubMed] [Google Scholar]
9. Wu C.-I., Postema P.G., Arbelo E. SARS-CoV-2, COVID-19 and inherited arrhythmia syndromes. Heart Rhythm. 2020;17:1456–1462. [PMC free article] [PubMed] [Google Scholar]
10. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-safety-a ... setting-or. Accessed April 26, 2020.
11. COVID-19 statistics Illinois Department of Health Web site. https://www.dph.illinois.gov/covid19/covid19-statistics Accessed April 29, 2020.
12. Yancy C.W. COVID-19 and African Americans. JAMA. 2020;323:1891–1892. [Google Scholar]
13. Giudicessi J.R., Roden D.M., Wilde A.A.M., Ackerman M.J. Classification and reporting of potentially proarrhythmic common genetic variation in long QT syndrome genetic testing. Circulation. 2018;137:619–630. [PMC free article] [PubMed] [Google Scholar]
14. Burke A., Creighton W., Mont E. Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks. Circulation. 2005;112:798–802. [PubMed] [Google Scholar]
15. Sun A.Y., Koontz J.I., Shah S.H. The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction. Circ Cardiovasc Genet. 2011;4:163–168. [PMC free article] [PubMed] [Google Scholar]
16. Plant L.D., Bowers P.N., Liu Q. A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. J Clin Invest. 2006;116:430–435. [PMC free article] [PubMed] [Google Scholar]
17. Splawski I., Timothy K.W., Tateyama M. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002;297:1333–1336. [PubMed] [Google Scholar]
18. Akylbekova E.L., Payne J.P., Newton-Cheh C. Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: the Jackson Heart Study. Am Heart J. 2014;167:116–122.e111. [PMC free article] [PubMed] [Google Scholar]
19. Van Norstrand D.W., Tester D.J., Ackerman M.J. Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome. Heart Rhythm. 2008;5:712–715. [PMC free article] [PubMed] [Google Scholar]
20. Bennett P.B., Yazawa K., Makita N., George A.L., Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995;376:683–685. [PubMed] [Google Scholar]
21. Wang D., Hu B., Hu C. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. [PMC free article] [PubMed] [Google Scholar]
22. Zhou F., Yu T., Du R. Clinical course and risk factors for mortality of adult inpatients with COVID19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. [PMC free article] [PubMed] [Google Scholar]
23. Shi S., Qin M., Shen B. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5:802–810. [PMC free article] [PubMed] [Google Scholar]
24. Guo T., Fan Y., Chen M. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5:811–818. [PMC free article] [PubMed] [Google Scholar]
25. Driggin E., Madhavan M.V., Bikdeli B. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic. J Am Coll Cardiol. 2020;75:2352–2371. [PMC free article] [PubMed] [Google Scholar]
26. Akhmerov A., Marban E. COVID-19 and the heart. Circ Res. 2020;126:1443–1455. [PMC free article] [PubMed] [Google Scholar]
27. Lazzerini P.E., Boutjdir M., Capecchi P.L. COVID-19, arrhythmic risk and inflammation: mind the gap! Circulation. 2020;142:7–9. [PubMed] [Google Scholar]
28. Makielski J.C. Late sodium current: a mechanism for angina, heart failure, and arrhythmia. Trends Cardiovasc Med. 2016;26:115–122. [PMC free article] [PubMed] [Google Scholar]
29. Belardinelli L., Giles W.R., Rajamani S., Karagueuzian H.S., Shryock J.C. Cardiac late Na(+) current: proarrhythmic effects, roles in long QT syndromes, and pathological relationship to CaMKII and oxidative stress. Heart Rhythm. 2015;12:440–448. [PubMed] [Google Scholar]
30. Roden D.M., Harrington R.A., Poppas A., Russo A.M. Considerations for drug interactions on QTc in exploratory COVID-19 treatment. Circulation. 2020;141:e906–e907. [PubMed] [Google Scholar]
31. Giudicessi J.R., Noseworthy P.A., Ackerman M.J. The QT interval: an emerging vital sign for the precision medicine era? Circulation. 2019;139:2711–2713. [PubMed] [Google Scholar]
32. Mitra R.L., Greenstein S.A., Epstein L.M. An algorithm for managing QT prolongation in coronavirus disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin: possible benefits of intravenous lidocaine. HeartRhythm Case Rep. 2020;6:244–248. [PMC free article] [PubMed] [Google Scholar]
33. Kaab S., Crawford D.C., Sinner M.F. A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes. Circ Cardiovasc Genet. 2012;5:91–99. [PMC free article] [PubMed] [Google Scholar]
34. Wang M., Cao R., Zhang L. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30:269–271. [PMC free article] [PubMed] [Google Scholar]
35. Traebert M., Dumotier B., Meister L., Hoffmann P., Dominguez-Estevez M., Suter W. Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells. Eur J Pharmacol. 2004;484:41–48. [PubMed] [Google Scholar]
36. Stas P., Faes D., Noyens P. Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. Int J Cardiol. 2008;127:e80–e82. [PubMed] [Google Scholar]
37. Yao X., Ye F., Zhang M. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clin Infect Dis. 2020;71:732–739. [PMC free article] [PubMed] [Google Scholar]
38. Chen C.Y., Wang F.L., Lin C.C. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006;44:173–175. [PubMed] [Google Scholar]
39. Chen F., Chan K.H., Jiang Y. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31:69–75. [PMC free article] [PubMed] [Google Scholar]
40. Cao B., Wang Y., Wen D. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020;382:1787–1799. [PMC free article] [PubMed] [Google Scholar]
41. Soliman E.Z., Lundgren J.D., Roediger M.P., INSIGHT SMART Study Group Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations. AIDS. 2011;25:367–377. [PMC free article] [PubMed] [Google Scholar]
42. Giudicessi J.R., Ackerman M.J. Azithromycin and risk of sudden cardiac death: guilty as charged or falsely accused? Cleve Clin J Med. 2013;80:539–544. [PMC free article] [PubMed] [Google Scholar]
43. Arellano-Rodrigo E., Garcia A., Mont L., Roque M. Torsade de pointes and cardiorespiratory arrest induced by azithromycin in a patient with congenital long QT syndrome [in Spanish] Med Clin (Barc) 2001;117:118–119. [PubMed] [Google Scholar]

[admin]

Timeline: Tracking Trump alongside scientific developments on hydroxychloroquine
The president touts the drug, but it hasn't proven effective against COVID-19.
by Libby Cathey
ABC News
August 8, 2020, 5:12 AM

African Americans account for 26% of confirmed COVID-19 cases but 43% of COVID-19 deaths....COVID-19 mortality rates in predominantly black counties are 6-fold higher than that in predominantly white counties....

Current evidence supports the notion that the common ion channel variants p.Asp85Asn-KCNE1 and p.Ser1103Tyr-SCN5A confer an increased risk of DI-LQTS and DI-SCD (Table 1 ).13 Importantly, p.Ser1103Tyr-SCN5A is seen almost exclusively in individuals of African descent and its frequency in that population (∼8%) is higher than that of p.Asp85Asn-KCNE1 (0.2%–2.5% depending on ancestry; 0.2% in individuals of African origin)...

Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death.

-- SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr, by Stacy AS Killen, Jennifer Kunic, Lily Wang, Adele Lewis, Bruce P Levy, Michael J Ackerman & Alfred L George Jr.

In individuals of African descent, the common SCN5A-encoded Nav1.5 sodium channel variant p.Ser1103Tyr-SCN5A has been associated with an increased risk of VA/SCD.14 , 15 , 17 Of note, this proarrhythmic potential has been reported to be enhanced by nongenetic risk factors known to reduce cardiac repolarization reserve (eg, hypokalemia and QTc-prolonging medication exposure....p.Ser1103Tyr-SCN5A is overrepresented in African American sudden infant death syndrome decedents...p.Ser1103Tyr-SCN5A confers an increased risk of sudden death in African Americans regardless of age....

Direct and/or indirect myocardial injury/stress, as assessed by cardiac biomarkers such as troponin I and brain-type natriuretic peptide, has emerged as both a prominent and a prognostic feature in COVID-19. Of note, in an adjusted Cox regression model, the mortality risk associated with elevated cardiac biomarkers/acute cardiac injury was more significant than age and high-risk comorbid conditions such as chronic obstructive/fibrotic pulmonary disease, diabetes, and a history of cardiovascular disease....

p.Ser1103Tyr-SCN5A could produce a similar African American–specific susceptibility to hypoxia-induced VA/SCD in the setting of SARS-CoV-2 infection/COVID-19....

Unfortunately, the increased risk of VA/SCD linked to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant is likely not limited to the possibility of hypoxia-induced VA/SCD. As succinctly outlined in recent work by Lazzerini et al,27 the exaggerated immune response triggered by SARS-CoV-2 infection, specifically elevation of IL-6, likely increases arrhythmia risk via (1) modulation of cardiac ion channel expression/function leading to APD prolongation (eg, direct IL-6–mediated blockade of hERG/Kv11.1 potassium channels), (2) cardiac sympathetic nervous system hyperactivity, and (3) inhibition of cytochrome P450 enzymes involved in the metabolism of some QTc-prolonging drugs (eg, IL-6 and CYP3A4) (Figure 1). The latter effect of IL-6 is particularly important given that a number of COVID-19 pharmacotherapies (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir) under investigation and/or in use clinically are known to prolong the QTc interval and predispose to DI-TdP/DI-SCD ...

these data suggest that 1 in 13 African Americans may be at a substantially increased risk of potentially lethal VAs, most notably DI-TdP, during the COVID-19 pandemic because of the perfect storm of (1) intrinsic genetic susceptibility (ie, p.Ser1103Tyr-SCN5A), (2) modifiable environmental risk factors (eg, electrolyte abnormalities and concurrent QTc-prolonging drug use), and (3) COVID-19–specific risk factors (eg, profound hypoxemia and cytokine storm) (Figure 1). Whether population-specific genetic risk factors such as p.Ser1103Tyr-SCN5A are contributing to the spike in sudden deaths and racial health disparities observed in COVID-19 epicenters remains to be proven, and given the lack of banked DNA in these epicenters, this speculation may not even be testable.

Nevertheless, given the potential for COVID-19 to exacerbate known gene-environment interactions pertaining to the potentially proarrhythmic p.Ser1103Tyr-SCN5A common variant, it seems reasonable (1) to avoid using COVID-19–directed QTc-prolonging drugs (eg, hydroxychloroquine ± azithromycin and lopinavir/ritonavir)...

A potentially pro-arrhythmic common variant, p.Ser1103Tyr-SCN5A, present in 1 out of 13 individuals of African descent has the potential to increase the risk of drug- and hypoxia-induced ventricular arrhythmias/sudden cardiac death and contribute to observed racial health disparities in the COVID-19 pandemic. As such, the use of unproven, QTc-prolonging COVID-19-directed therapies, most notably the combination of hydroxychloroquine and azithromycin, should be limited.

-- Genetic susceptibility for COVID-19–associated sudden cardiac death in African Americans
by John R. Giudicessi, MD, PhD, Dan M. Roden, MD, Arthur A.M. Wilde, MD, PhD, and Michael J. Ackerman, MD, PhD

President Donald Trump's continued embrace of hydroxychloroquine, an anti-malaria drug with unproven efficacy against the novel coronavirus, directly contradicts guidance from the nation's top public health agencies and officials.

Approved decades ago to prevent and treat malaria, the prescription medicine hydroxychloroquine and a similar drug chloroquine are used to treat autoimmune diseases like lupus and rheumatoid arthritis.

But the drugs have not shown to benefit coronavirus patients or proved effective as a prophylactic, according to the Food and Drug Administration, National Institutes of Health and scientific community at-large -- despite the president's persistent push.

Here's a timeline illustrating Trump's longstanding battle with health experts alongside scientific developments on hydroxychloroquine during the pandemic:


The drug hydroxychloroquine, pushed by President Donald Trump and others in recent months as a possible treatment for people infected with the coronavirus disease (COVID-19), is displayed by a pharmacist at the Rock Canyon Pharmacy in Provo, Utah, May 27, 2020.

March 19: Trump declares drug a 'game changer'

As parts of the country start shutting down in an effort to curb virus spread, Trump announces the FDA will fast-track approval of unproven coronavirus treatments, including chloroquine and hydroxychloroquine.

"The nice part is, it's been around for a long time, so we know that if it -- if things don't go as planned, it's not going to kill anybody," Trump says at a task force briefing.

The drugs are already in short supply in the U.S., as word spreads of their potential benefit to COVID-19 patients. Manufacturers say they are ramping up production.

March 20: Trump banks on 'a feeling' as Fauci calls evidence 'anecdotal'

Director of the National Institutes of Allergy and Infectious Diseases Dr. Anthony Fauci says, "the answer is no" when asked at a task force briefing if hydroxychloroquine is an effective coronavirus treatment, explaining signs of the drug's promise were purely "anecdotal evidence."

"But I'm a big fan, and we'll see what happens," Trump steps forward to add. "I feel good about it. That's all it is, just a feeling, you know."


President Donald J. Trump listens as Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, speaks with members of the coronavirus task force, April 22, 2020 in Washington, DC.

March 21: Trump cites success of small French study, publisher later says data 'did not meet its standards'

Trump tweets to his roughly 84 million followers that hydroxychloroquine taken with the antibiotic azithromycin could be "one of the biggest game changers in the history of medicine" and should "be put in use immediately."

He cites a French study of three dozen patients published in the International Journal of Antimicrobial Agents on March 17. Twenty patients took hydroxychloroquine and just six received the combo.

The publisher issues a notice two weeks later saying the study "does not meet the Society's expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety."

....be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE! @US_FDA @SteveFDA @CDCgov @DHSgov

— Donald J. Trump (@realDonaldTrump) March 21, 2020

March 24: Arizona man dies after ingesting non-medication chloroquine

A man in Arizona dies after ingesting a form of chloroquine used to clean fish tanks in an apparent attempt to self-medicate for the coronavirus, according to hospital system Banner Health.

"I had it in the house because I used to have koi fish," she says. "I saw it sitting on the back shelf and thought, 'Hey, isn't that the stuff they're talking about on TV?'"

March 28: FDA approves emergency use of hydroxychloroquine

The FDA issues an emergency use authorization to allow "hydroxychloroquine sulfate and chloroquine phosphate products" donated to the Strategic National Stockpile to be distributed to hospitalized patients with COVID-19.

The agency says the drugs will be distributed to certain patients when clinical trials are not feasible.

April 5: Trump on hydroxychloroquine: 'What really do we have to lose?'

The president doubles down on his defense of hydroxychloroquine, acknowledging he's "not a doctor" but has seen "good signs."

"We don't have time to go and say, 'Gee, let's take a couple of years and test it out. And let's go and test with the test tubes and the laboratories,'" Trump says at a task force briefing.

"If it works, that would be great," he adds. "But it doesn't kill people."


President Donald Trump speaks to reporters following a meeting of his coronavirus task force in the Brady Press Briefing Room at the White House on April 6, 2020 in Washington, DC.

April 8: Medical societies warn of COVID-19 combo

The American Heart Association, the American College of Cardiology and the Heart Rhythm Society warn in a joint guidance that the combination of hydroxychloroquine and azithromycin may not be appropriate for patients with existing heart problems.

"We are united in our mission to achieve optimal, quality care for our patients, and we must continue to be vigilant in assessing the potential complications of all medications during this crisis," says Dr. Athena Poppas, president of the American College of Cardiology.

April 9: NIH begins clinical trials of hydroxychloroquine

The National Institutes of Health begins a clinical trial to test the effectiveness of hydroxychloroquine in treating coronavirus with patients enrolled in Tennessee.

The study, later dismantled, was not estimated to be completed until July 2021.

April 13: Study in Brazil linking hydroxychloroquine to fatal heart problems makes headlines
A small research trial in Brazil abruptly ends after coronavirus patients taking a higher dose of chloroquine in combination with azithromycin developed irregular heart rates.

Within three days of beginning treatment, researchers started noticing heart arrhythmias in patients taking the higher dose of chloroquine. By the sixth day, 11 had died.

While meeting with recovered coronavirus patients at the White House, some of whom had taken hydroxychloroquine, Trump praises the drug as "an unbelievable malaria pill" and an "unbelievable lupus pill."

"We have tremendous endorsements, but if it was somebody else other than President Trump that put it forward, if some other person put it forward that said, 'Oh, let's go with it.' You know, what do you have to lose?" Trump says.

April 22: Vaccine chief ousted

The head of the federal agency charged with overseeing the rapid production of a coronavirus vaccine says he's removed from his post after trying to push back on problems he saw infecting the federal response, including being handed "misguided directives" to push the drugs chloroquine and hydroxychloroquine.

Dr. Rick Bright says in a statement his transfer was retaliation "in response to my insistence that the government invest the billions of dollars allocated by Congress to address the COVID-19 pandemic into safe and scientifically vetted solutions, and not in drugs, vaccines and other technologies that lack scientific merit."


Dr. Richard Bright, former director of the Biomedical Advanced Research and Development Authority, testifies during a House Energy and Commerce Subcommittee on Health hearing to discuss protecting scientific integrity in response to the coronavirus outbreak, May 14, 2020. in Washington, D.C.

April 24: FDA warns against hydroxychloroquine use outside hospitals
The FDA issues a warning against using hydroxychloroquine outside of a hospital setting or clinical trial due to the risk of heart rhythm problems.

The agency says in a statement that the treatment has "not been shown to be safe and effective for treating or preventing COVID-19."

"Hydroxychloroquine and chloroquine can cause abnormal heart rhythms such as QT interval prolongation and ventricular tachycardia. These risks may increase when these medicines are combined with other medicines known to prolong the QT interval, including azithromycin," the FDA says.


President Donald Trump gestures to Vice President Mike Pence as Stephen Hahn, commissioner of the U.S. Food and Drug Administration, steps back to the podium to answer a question during a briefing about the coronavirus in the James Brady Press Briefing Room of the White House, April 24, 2020.

April 26: Despite FDA warning, states stockpile hydroxychloroquine

As hospitalizations surge, state and local governments across the country obtain roughly 30 million doses of hydroxychloroquine, despite warnings more research is required.

At least 22 states and Washington, D.C., secure shipments of the drug, but health experts worry having it widely available could make it easier to misuse, The Associated Press reports.

May 11: Study shows hydroxychloroquine associated with cardiac arrest

The results of a retrospective study published in the Journal of the American Medical Association show that hydroxychloroquine is not effective against COVID-19 and is associated with cardiac arrest.

Researchers examined more than 1,400 patients with COVID-19 in New York City area hospitals found that patients treated with hydroxychloroquine had a similar death rate to those not treated with the drug.

When patients received a combination treatment of hydroxychloroquine and an antibiotic, the combo Trump promoted, they were more than twice as likely to experience cardiac arrest as those who took neither drug.

May 18: Trump says he's been taking hydroxychloroquine

The president says he's taking hydroxychloroquine in an effort to ward off the coronavirus, despite the FDA warning it should only be administered for COVID-19 in a hospital or research setting.

"At some point, I'll stop. What I'd like to do is, I'd like to have the cure and/or the vaccine, and that'll happen, I think, very soon," he says.


President Donald Trump speaks during a meeting with restaurant industry executives about the coronavirus response, in the State Dining Room of the White House, May 18, 2020.

May 24: Trump says he's finished taking hydroxychloroquine and is 'still here'

Trump tells "Full Measure with Sharyl Attkisson" that he "just finished" his two-week regimen of hydroxychloroquine and zinc and continues to claim "hydroxy" has had "tremendous, rave reviews."

"And by the way, I'm still here," he adds.

May 28: Prescriptions for hydroxychloroquine on rise

Research published in JAMA finds that during the 10-week period from Feb. 17 to April 27 doctors wrote approximately 483,000 more prescriptions for hydroxychloroquine than in the same time period in 2019.

Researchers says the surge is "likely due to off-label prescriptions for COVID-19."

June 15: FDA revokes its emergency use authorization

The FDA revokes emergency use authorization for chloroquine and hydroxychloroquine citing in a statement that the drugs are "unlikely to be effective in treating COVID-19 for the authorized uses."

"Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use," it continues.

The federal government has now stockpiled millions of excess doses of the drug.

Peter Navarro, a trade adviser to Trump who helped distribute the drug tells The New York Times in response: "This is a Deep State blindside by bureaucrats who hate the administration they work for more than they're concerned about saving American lives."


Peter Navarro appears on "Good Morning America," July 29, 2020.

June 20: NIH ends hydroxychloroquine trials

The NIH abandons clinical trials of the drug after finding that hydroxychloroquine "was very unlikely to be beneficial to hospitalized patients with COVID-19," the organization says in a statement.

"Study shows treatment does no harm, but provides no benefit," the NIH says.

July 1: FDA publishes findings of safety issues

Two weeks after revoking emergency use authorization of the drug, the FDA publishes a summary of safety issues tied to using hydroxychloroquine and chloroquine to treat patients hospitalized with COVID-19.

It includes "reports of serious heart rhythm problems and other safety issues, including blood and lymph system disorders, kidney injuries, and liver problems and failure."

July 28: Trump tweets video on hydroxychloroquine flagged by Twitter as misleading

Twitter flags and later takes down a video retweeted by Trump and directly shared by Donald Trump Jr. that featured a woman identifying as a doctor promoting hydroxychloroquine as a COVID-19 "cure," for violating the company's policies on misinformation related to the pandemic.

Donald Trump Jr.'s account is "temporarily limited" for the action, a Twitter spokesperson confirms.

That same morning, Fauci tells "Good Morning America" that clinical trials have shown hydroxychloroquine is "not effective."


Dr. Anthony Fauci appears on "Good Morning America," on July 28, 2020.

"The overwhelming, prevailing clinical trials that have looked at the efficacy of hydroxychloroquine have indicated that it is not effective in coronavirus disease," Fauci says.

Aug. 2: Another task force doctor says he 'can't recommend' hydroxychloroquine

Assistant Secretary of Health Adm. Brett Giroir, who was tasked in March to lead the administration's testing efforts, tells NBC News he "can't recommend that as a treatment" when asked about the increasingly controversial drug.

"We need to move on from that and talk about what is effective," he says. "At this point in time, we don't recommend that as a treatment."

Aug. 3: Trump doubles down

The president continues to claim hydroxychloroquine has been criticized as a treatment "because I supported it."

"Hydroxy has tremendous support, but politically it is toxic, because I supported it. If I would have said, 'Do not use hydroxychloroquine under any circumstances,' they would have come out and they would have said it's a great thing," Trump tells White House reporters.


President Donald Trump calls on a reporter during a briefing in the James Brady Press Briefing Room of the White House, Aug. 5, 2020.

Aug. 4: FDA commissioner notes 'politicization' of hydroxychloroquine

FDA Commissioner Stephen Hahn tells ABC News' Chief Anchor George Stephanopoulos in an interview with "Good Morning America" that the decision to take hydroxychloroquine should "rest with physicians and patients" in privacy.

"There's been a lot of politicization, or political political back-and-forth about this, and George, this is about science and data. There are randomized trials that show that it doesn't work. There are observational trials that show that it might work," he says. "And we've put out information that we want doctors to have about both the safety and the risks, as well as the potential of benefits or not."

"I have had conversations with the president about this," Hahn adds, "and the president's been very clear: It might work, it might not."

[admin]

Part 1 of 3

The Good, the Bad and the Ugly: a review of SARS Lab Escapes
by Gilles Demaneuf
Nov 16, 2020

Research by DRASTIC, a group of researchers working together to investigate the origins of SARS-CoV-2, starting from facts and not bending to any pressure. DRASTIC members were the first ones to discover the Mojiang ‘miners’ story.
DOI: 10.5281/zenodo.4293257

Introduction

In 2003–04, in the wake of the SARS epidemics, there were multiple cases of laboratory acquired infection (LAI) with SARS in just a few months: first in a P3 in Singapore, then in a P3 lab that was part of a military P4 complex in Taipei, and last a protracted case in a P3 in Beijing. The ‘WHO SARS Risk Assessment and Preparedness Framework’ has a good summary of these lab accidents:

Since July 2003, there have been four occasions when SARS has reappeared. Three of these incidents [note: Singapore, Taipei and Beijing] were attributed to breaches in laboratory biosafety and resulted in one or more cases of SARS. The most recent laboratory incident [note: in Beijing] resulted in 9 cases, 7 of which were associated with one chain of transmission and with hospital spread. Two additional cases at the same laboratory with a history of illness compatible with SARS in February 2004 were detected as part of a survey of contacts at the facility. [i.1]

This article reviews some of these cases and discusses briefly some of the insights that were gained from these at the time.

1. The Good: Singapore P3 — Sep 2003

In a few words: This first SARS LAI accident (in Singapore) exposed some serious structural biosafety issues but the investigation was very thorough and transparent, and even extended into a review of all BSL-3s in the city-state. The Singapore government used it as an opportunity to fundamentally redesign its biosafety approach, just at the time when more BSL-3s were due to come in line. We also note that the (strongly controlled) local media do not seem to have contributed any additional details to the story.

1.1 The Accident:

In September 2003, a 27-year-old student from the National University of Singapore (NUS) was found to be infected with the SARS virus due to improper experimental procedures. [s.1]

The student was in his third year of a doctoral program in microbiology and was studying the replication of flaviviruses such as the West Nile Virus (which was just causing a peak of infection in the US at the time) in cells using electron microscopy. So far he had worked at the NUS BSL- 2 with the attenuated Sarafend strain of the West Nile virus. Because he wanted to compare this attenuated train with the more pathogenic New York strain of the virus (that one a BSL-3 pathogen), and since NUS had no BSL-3, an agreement was made for him to do this work at the BSL-3 facility of Institute of the Environmental Health Institute (EHI) of Singapore.

The BSL-3 of the EHI had been heavily involved in SARS research during the recent outbreak and was continuing that work at the time [s.6].

The student had no previous experience working in a BSL-3. On his first visit to the EHI, he was given only 20 minutes training with BSL-3 procedures before entering the BSL-3 lab.

On his second and last visit to the institute (Saturday 23 Aug 2003) he entered the lab 3 times:

• The first time, he went in with the technician, wearing only street clothes, and did not engage in any work.

• The second time, staff of the EHI were meeting. Before going to that staff meeting, the virology technician had grown up a stock of the New York isolate and centrifuged the supernatant from infected cells. The technician had then placed the centrifuge tubes in the Class II biological safety cabinet for the student to ampoule as a seed stock for his research. Accordingly the student put on a gown and two sets of gloves before entering the laboratory alone, where he spent 20 minutes unsupervised, transferring the cell supernatant into pre-labelled cryovials under the Class II biosafety hood. [s.6]

• The third time he re-entered the lab with the technician who was back from her meeting and transferred the cryovials to a –70°C freezer located in the BSL-2 facility, as no such freezer existed inside the BSL-3 laboratory, so that all frozen BSL-3 virus strains were effectively stored in the BSL-2 freezer.

The student did not engage in any more work with these before falling ill 3 days later on Aug 26, developing

The student did not engage in any more work with these before falling ill 3 days later on Aug 26, developing mild SARS symptoms. He sought outpatient medical care from his general practitioner, Singapore General Hospital (SGH) emergency room and a Chinese physician. He eventually returned to the SGH with persistent fevers and was admitted to the hospital on Sep 3. Fortunately he recovered and there were no secondary cases.

1.2 The Investigation:

Analysis of the ampoules of seed West Nile virus that the student stored on that 23rd Aug showed that the vials contained SARS- CoV as well as West Nile virus. That SARS-CoV matched the SARS isolate that was handled at the EHI.

Poor record keeping made it difficult to ascertain if there was a live SARS virus in the BSL-3 laboratory on that exact 23rd Aug, but it was established that there was some there 2 days before. [s.8]

In other words there had been a SARS-contamination within the BSL-3.

A 11-member review panel led by Antony Della-Porta, Biosafety Expert for the WHO [t.3], produced a report for the Ministry of Health in Singapore. The panel concluded that a combination of

“inappropriate laboratory standards and a cross-contamination of West Nile virus samples with SARS coronavirus in the laboratory led to the infection of the doctoral student”.[s.8]

The investigators also documented a variety of shortcomings within the EHI BSL-3 lab that most likely contributed to the incident. These included inadequate record-keeping procedures, totally inadequate training, inexistent virus stock inventory, patchy maintenance records plus a variety of structural problems including the absence of gauges to indicate the pressure differentials, the lack of a freezer to store samples, problems with HEPA filters and air supply, and other equipment deficiencies. [s.5, s.8].

Accordingly they first recommended that all BSL-3 work cease there ‘until the laboratory deficiencies have been addressed and subjected to external audit’. [s.8]

Note: While many circumstantial evidences pointed to a real risk of SARS contamination of the EHI BSL-3 lab, the exact causes of this particular accident — such as a precise bad manipulation or the failure of a precise piece of equipment — was never precisely identified.

1.3 Structural Issues:

At the invitation of the Singapore Ministry of Health, the investigation team went further than the EHI P3 lab and looked also at overall biosafety practices in other Singapore institutions. This was both a very courageous and very useful initiative, especially in view of the large number of new Singapore BSL-3 labs that were supposed to come in line soon at the time.

The Singapore General Hospital BSL-3, the NUS BSL-2 and the Defence Science Organisation were reviewed. The panel found deficiencies at the Singapore General Hospital as well as at the NUS BSL-2. [s.8] and made recommendations to improve biosecurity in each institution they visited.
More generally, the panel concluded that there were no appropriate standards, regulations or guidelines on biosafety in Singapore, and offered some recommendations [s.8] as to what could be done to rectify the situation:

Biological Standards

Recommendation 7.1: Need for a National Legislative basis for Standards in Biosafety Laboratories for Singapore.[..].

Recommendation 7.2: A structure should be created for laboratory certification covering both structure integrity and operating procedures. [..]

Recommendation 7.3: Creation of the tracking system for importation, exportation to and from Singapore. [..]

1.4 The Aftermath:

At the end of September, Lim Ruisheng, Minister of Environment of Singapore, apologised to the people of Singapore for the SARS infection incident in the laboratory of the Institute of Environmental Health. Lin Ruisheng said:

“The Environmental Health Research Institute must take responsibility, and the National Environmental Administration must also take responsibility. As the Minister of Environment, I should be more responsible. Because the investigation results of the investigation team show that our laboratory is indeed not safe enough.” [s.3]

Since 2003, Singapore has introduced legislation and regulations to cover the handling of high risk infectious agents and developed a laboratory accreditation system. Aligning incentives with regulation and training, they have also taken a number of initiatives to reward outstanding safety practices.[s.6]

2. The Bad: Taiwan Military P4 — December 2003

Ina few words: The second SARS LAI accident (Taiwan) was a less straightforward affair. First the human factor played a big role in delaying notification to the authorities. Then the accident had a large epidemic potential as it involved international air-travelling shortly after infection. Also, while the official reporting of the accident was generally transparent, a few aspects of the story remained somewhat opaque due to the military setting.

Taiwanese media, and interestingly also mainland China media, have contributed circumstantial details to the story. Generally, the reaction of the authority seems to have been earnest and constructive.

2. 1 The Accident:

Oddly most references to this lab accident simply fail to mention that it happened in a military P4 laboratory (likely built or equipped by France) utilising type III glove ported isolators [t.17]. These facts are particularly important and should be better publicised.

This lab escape involved the Taiwan Military Institute of Preventive Medical Research (IPMR) of the National Defence University. It is located in Baiji Mountain, Sanxia (or Sanhsia, 三峽, Three Georges), on the outskirts of Taipei Town, ands is allegedly partly dug into the hill. The laboratory is known as the centre of Taiwan’s biochemical capacities. The facility was allegedly capable of producing weapons-grade biological agents [t.1] and may have done so in the past [t.18], although Taiwanese officials claim it exists only to research ways of preventing biological attacks from mainland China.

According to unverified Chinese sources, Taiwan purchased the IPMR from France in 1983 [t.2]. A more recent Western source described it as being ‘full of advanced French-made equipment’ [t.18]


IPMR entrance

As the top biosafety lab in Taiwan, the IPMR has been racing against the clock to analyze the characteristics of the virus since the SARS outbreak. In May 2003 President Chen Shui-Bian had announced that he had ordered the IPMR to work on a vaccine for SARS. [t.18, t.20]

On December 6th 2003, 44-year-old Lieutenant-Colonel Chan Jiacong , a Ph.D. in pathology from Johns Hopkins University (US), contracted SARS at the IPMR due to negligence.

The researcher worked with SARS. He was cleaning his Taipei lab when he found a ripped bag [t.7] in the negative-pressure transport cabinet of the laboratory. He assumed that the bag had been leaking for several days and may have thought the virus had already lost its effectiveness. In any case the researcher was working alone and had to travel to Singapore the next day to address a meeting about his SARS research, so he was in a rush t.4, t.10]. [Note: we were unable to identify a suitable conference in Singapore on those days — suggestions welcome]

The proper way of cleaning that spill was to use vaporised hydrogen peroxide, but this would have taken hours. Instead he decided to use a shortcut in the form of 70% ethanol which he could spray on the spill before wiping it out [t.17].

As he could not reach the spot with the gloves attached to the cabinet, he instead wore a “normal mask” and surgical gloves, no protective gown, opened the transport cabinet, tried to reach the spill — but because he still could not reach it, he then put his head inside the cabinet pass-through to spray the spill with the ethanol mix. After spraying it and waiting for 10 minutes, he wiped the spill out.

In the process it seems that he then simply dumped the leaking bag on his trash cart.[t.2, t.7, t.8, t17].

“He was in a hurry to get ready for a conference in Singapore, so he was rushing to finish his disinfection work and was careless”

-- Su Ih-jen, chief of Taiwan’s Center for Disease Control [t.5]

Another source notes that:

[The] laboratory was also found to have violated many safety and record-keeping standards. For example, this researcher regularly worked long shifts (12 to 14 hours) usually alone and there was no timely procedure in place for reporting incidents. In addition, there was no record of him actually working in the laboratory since he had recently lost his building access card and was using a borrowed card on the date of the incident.

Della-Porta explains that the recommended procedure for decontamination of the safety cabinets used in the Taiwan facility is the use of a hydrogen peroxide generator, which takes several hours. He adds that a shortcut of 70 percent ethanol for 10 minutes is completely inadequate. In addition, there were inadequate standard operating procedures and Taiwan was without guidelines or regulations related to biological safety.’ [t.10]

Example of a mobile Class III BSC (Biosafety Cabinet) — suitable for a BSL-4

On the following day, Dec. 7, he flew to Singapore with six laboratory colleagues on a China Airlines flight. He complained of fatigue and muscle pain on Dec. 8 while in Singapore but had no fever until the night of Dec. 10 after he returned to Taipei. He later had diarrhoea.

Soon after returning from Singapore, he reported to the Defence University clinic that he had developed influenza. Among many issues, the WHO investigation team recorded a failure to have a medical monitoring programme in place. Indeed senior management could not explain why, after Chan had reported to the Defence University clinic with a respiratory disease, he was not followed up for the next 6 days when he was absent from work. [t.16]

2.2 Fear of Losing face and bringing shame:

Faced with the standard symptoms of SARS, Lieutenant-Colonel Chan was very aware that he may have caught SARS. However he decided to self-isolate at home, relying on his father to care for him, as he was unwilling to seek medical care because he dreaded bringing disgrace to himself and his institution.

His father eventually persuaded him [t.6] to seek medical attention by threatening to commit suicide. He checked into Taiwan Hoping Hospital only on Dec 16 by which time he had developed other SARS symptoms, such as a cough and signs of pneumonia. He was readily diagnosed as having SARS [t.16].

His father said in a television interview that his son knew early on that he might have SARS. But he delayed going to the hospital because he didn’t want to panic the public and disgrace Taiwan. He quarantined himself at home until Dec. 16 and relied on his father for food and other care.

His father told CTI cable TV that his son: “wanted to die at home because he feared his illness would bring shame to his lab and the country”.

The father said he pleaded with his son to seek treatment. As the scientist’s condition worsened, his father said he threatened to commit suicide if he didn’t get help. “He finally agreed to go to the hospital after I threatened to kill myself,” his father said. “He was thinking of the country. He’s a military man, and military men are bound by a natural duty.” [t.6]

2.3 Reaction from the Authorities

A chest x-ray showed pneumonia in his right lung and polymerase chain reaction tests of throat and blood samples were positive for the SARS virus. The finding was further confirmed on multiple samples in two laboratories in Taipei.

Six colleagues were ordered to suspend work at the laboratory and start self-isolation at home for 21 days. The four family members of the officer self-isolated at home for 21 days, although they had not displayed fever or any other SARS-like symptoms.

Although Chan was not in the contagious phase when he travelled, around 95 people who had been in contact with him were quarantined until Dec. 23, including 19 that were on his flights and 79 in Singapore. None of them were infected. It is worth noting that officials were having difficulty contacting three Americans, a Japanese and a Singaporean who had been on the flight. Additionally two of his colleagues went to Singapore with the researcher on Dec. 7 and later traveled to the United States.[t.6, t.14]

Five foreigners — three Americans, one Japanese and a Singaporean — who sat near him on the return flight from Singapore have been located and told to monitor their health, officials said on Friday. The Japanese traveler was located in Taiwan where he lives, two of the Americans went to Hong Kong and the other is in the United States, said Shih Wen-yi, a spokesman for Taiwan’s Center for Disease Control. They were told to be on alert for SARS symptoms, like a fever. [t.6]

Lieutenant Colonel Chan leaving hospital

The Taiwan Science Council closed the IPMR temporarily and issued a resolution stating that Lieutenant Colonel Chan violated the “Laboratory Safety Guidelines and Norms” of the SARS project research plan and was given a sanction not to apply for research project funding.

The laboratory conducting severe acute respiratory syndrome (SARS) research at the Institute of Preventive Medicine Research (IPMR) of the National Defence Medical College was closed down temporarily Wednesday after one of its researchers was confirmed to have contracted the flu-like disease, military sources said.[t.6]

“All SARS research work in the military has also been halted”

-- Chang Sheng-yuan, director-general of Taiwan’s Military Medicine Bureau

The CDC conducted two complete environmental disinfections. All equipment was inspected in detail, and all personnel were retrained. [t.2, t.13]

Separately in China, authorities ordered all researchers to hand in SARS samples as a precaution. China’s Health Ministry told laboratories to send samples to “designated places for storage” and “demanded that all regions strengthen management of the SARS virus,” the official Xinhua News Agency said. [t.6]

2.4 WHO enquiry and international cooperation:

A WHO Team was invited to investigate the case. Anthony Della-Porta, who had earlier headed the WHO investigation of the SARS LAI assisted with the investigation.

As far as we can tell, the WHO investigation seems to have been rather comprehensive and transparent, finding and reporting quite a few failures, with the exact circumstances of the accident well delineated [t.13]. The international cooperation effort that followed seems to have been constructive and certainly helped rebuild trust in the Taiwanese capacity to manage their BSL3/4s:

In January 2004, the World Health Organization (WHO) dispatched an expert team [of 3] led by Dr. Antony Della-Porta to Taiwan because of the SARS case (Figure 1). They visited five existing and new constructions of BSL-3 laboratories during their short stay. In addition to the advice given to those individual laboratories, four major measures in terms of general management of biological safety were suggested.

Soon after, CDC invited two world-class experts in the field, Dr. Thomas Ksiazek from U.S. CDC and Dr. Kazuyoshi Sugiyama from National Institute of Infectious Diseases (NIID) of Japan, respectively, in March and November 2004, to give [Taiwan CDC] us a helping hand in inspecting current safety and management of equipment in laboratories of Biosafety Level 3 or above across Taiwan (Figure 2). [t.9]

Figure 1: WHO expertise committee investigated BSL-3 Virus laboratory of Taiwan CDC


Figure 2: Taiwan CDC invited experts from USA CDC and Japan NIID to Taiwan to assist in appraising BSL-3 laboratories

As the Taiwan CDC would later state,

‘The laboratory-acquired case of SARS in Taiwan sent a shockwave through the nation. However, this incident was a crucial turning point. It led to the seeking and adoption of advice from both national and international experts and scholars and, therefore, acquired invaluable learning experience in biological safety management’. [t.11]

2.5 Lessons to be learnt:

Henk Bekedam, the WHO representative in China, told reporters in Beijing that the case in Taiwan should alert scientists:

“It’s a clear reminder again that we have to be extremely cautious working with the SARS coronavirus and there are whole issues about whoever in the whole world is keeping a SARS specimen has to be very careful in dealing with this.” [t.6]

Anthony Della-Porta was even more clear:

“It hasn’t been a disaster, but it could have been.” [t.12]

As noted by Furmanski [t.15] (quoted here), this second outbreak further shook the virology communities in Asia, where many labs held and worked on SARS samples. On December 18, 2003 WHO released a new protocol for handling SARS specimens in the post-outbreak period, with special emphasis on reducing risk of and performing surveillance to detect laboratory infections. Although this protocol was clearly created after the first (Singapore) escape, the WHO chose its words carefully so as to avoid offending members but resolutely highlighted the laboratory risk-factor in its introduction:

“The possibility that a SARS outbreak could occur following a laboratory accident is a risk of considerable importance, given the relatively large number of laboratories currently conducting research using the SARS-CoV or retaining specimens from SARS patients. These laboratories currently represent the greatest threat for renewed SARS-CoV transmission through accidental exposure associated with breaches in laboratory biosafety.”

-- WHO [t.16]

3. The Ugly: Beijing P3 — February and April 2004

Ina few words: The third lab incident is a very unsatisfactory affair. It happened in the context of a rather toxic ivory-tower academic system leading to unchallenged bad practices. Very limited official information was released when it ever was; effectively the Chinese government, and consequently the investigation report, provided very little insights or simply did not discuss key issues.

There are also some reasons to suspect an internal cover up of the first two SARS cases, and last (and not least), the sanctions announced by the Chinese Ministry of Health seem to have been more symbolic than anything else.

Without exaggeration, the Beijing LAI accidents and the subsequent outbreak seem very much to be a story of towering academic ego, shocking incompetence, obstruction of the truth and lack of accountability.

More importantly the unchallenged poor-handling of the investigation by the Chinese authorities — after the WHO left the scene — may have set a bad precedent.

Partially redeeming this dark picture, it is worth noting that the mainland China media contributed some very good pieces of investigative journalism which can still be found today online and deliver many essential clues as to what actually happened.

3.1 Setting the wrong expectations:

Following the Singapore SARS lab accident it became clear that laboratories handling SARS may not be as safe as one could expect, especially in nations rushing to build more P3 labs. This raised the question of the safety of the laboratories handling SARS in China.

Around the 13th Oct 2003 (so before the SARS accident in Taiwan) the National Health and Family Planning Commission of the People’s Republic published an article where it stated that:

“The nation’s SARS virus laboratories are safe. At present, no SARS patient has been infected from a research laboratory virus.” [b.4, b.13]

But the article went on to list reasons to be anxious and to make sure that the nation redoubles its effort to better control all risk factors:

According to Professor Zhu Qingyu, a P3 qualification only refers to the laboratory’s compliance with physical protection standards. In fact, the human factor comes first in terms of laboratory safety.

“Without good quality and sense of responsibility, (scientific research institutions) without strict and perfect management, being designated a P3 laboratory alone will not work.“ [b.13]

On December 18 2003, two days after the revelation of the Taiwan SARS lab accident, the WHO called for vigilance in P3 settings studying SARS and issued its ‘biosafety guidelines for handling of SARS-CoV specimens and cultures’ [t.16].

On the same day, the Chinese Ministry of Health duly followed suit and issued an emergency notice requesting all localities to strengthen the centralised management of infectious SARS virus strains and human specimens to ensure the biological safety of virus laboratories and storage units [b.12].

The Ministry of Science and Technology and the Ministry of Health also conducted safety inspections of the 15 to 20 P3 laboratories across the country at the end of December and started addressing the issue of labs that were handling SARS without approval. [b.1, b.12]

Incidentally, the CDC Institute of Virology in Beijing, being the most famous P3 lab handling SARS in the country, was explicitly mentioned in the press at the time:

P3 laboratories have corresponding strict operating procedures. [ — ]. The current research on SARS by the Institute of Virology of the China Center for Disease Control and Prevention is under such a strict operation. SARS laboratories implement a dual access system: first, the procedures must be complete; second, entering the laboratory must be approved by management personnel.

It is reported that in the laboratory of the Institute of Virology of the Chinese Center for Disease Control and Prevention, there are six or seven researchers engaged in SARS research, and these people can be directly exposed to the SARS virus. According to Ruan Li [director of the institute], in accordance to the rules, when researchers enter the laboratory, they must first pass through an air-lock, then through the anti-contamination area, and finally through another air-lock. The same is true when one comes out.

All viruses are wiped out or removed in the process, and they cannot escape the laboratory. Therefore, the key lies in whether the staff strictly follow the procedures. [b.12]

Article from the 19th Dec 2003

On the 19th Dec, Qi Guoming, director of the Science and Education Department of the Ministry of Health of China, detailed the actions taken by his ministry in an interview with a reporter from CCTV:

The Ministry of Health is now dealing with these problems. The laboratories that began to conduct SARS virus research without approval are being cleaned up and checked.

He explained that the review teams will examine the laboratory’s hardware, personnel quality, and the management of virus samples. Those laboratories that do not meet the standards will immediately stop research. [ — ]

‘If an accident occurs and infection is caused, it is a crime against the people and society’. [b.12]

3.2 Flagship role of the CDC Institute of Virology:

The National Institute for Viral Disease Control and Prevention (NIVDC) in Beijing (病毒病预防控制所), in short the Institute of Virology, is part of the Chinese Center for Disease Control and Prevention (China CDC, 中国疾病预防控制中心 ).

The CDC itself had only been formed in early 2002 and had to immediately ride through the SARS epidemic. In June 2003, mainland China had no more new or active SARS cases and the SARS epidemic was officially declared as being over. The Institute of Virology was then designated by the Ministry of Health as one of the six storage units for the SARS virus. [b.1]

The Institute of Virology was effectively the most prestigious viral research institution in the country at the time. It had the first P3 in China, was the workplace of famous academicians and was part of the newly formed CDC, which very purpose was to prevent epidemics in the country.



Situated at №100 Yingxin Street, Xicheng District, the institute is 1km from the busy interchange station of Beijing metro lines 4 and 7. The main body of the virus institute was a five-story building (since rebuilt), the fifth floor was a dormitory for staff or visitors , and the remaining four floors were offices and laboratories [b.1].

From the appearance, the whole building was unremarkable. An old man who lived in the bungalow opposite the virus institute for more than 30 years told reporters that the virus centre was built in the 1950s [b.1].

To this day the building is still standing. The Institute main buildings are now at 155 Changbai Rd, Changping Qu, Beijing. But the old building is still part of the Institute. [b.517]

‘№100 Yingxin Street, Beijing still stood stubbornly in that old crowded alley. The windows of the building were covered with grey dust, many were broken, and the exhaust vents jutting from the laboratory pointed at the residents’ homes only a few meters apart.’ [b.3]

Main entrance of the Institute, 100 Yingxin Street — 2020


Side alleys — source: Baidu

At the time there was no logo of the Institute of Virology at the front of the office building [b.1]. Its nondescript appearance clearly contrasted with its flagship role in viral research.


5-storey building of the Institute where the leak happened, source: Baidu

3.3 An academic ego got hurt

The director of the Diarrhoea Virus Department was Academician Hong Tao (洪涛) of the Chinese Academy of Engineering. 72 y-old at the time and a highly respected virus expert, he was one of the main pioneers in the field of medical electron microscopy, the main founder of the virus morphology discipline in China, the discoverer of diarrhoea rotavirus (“洪氏腹泻” Hong’s Diarrhoea) which caused a acute diarrhoea outbreak in North China in 1983, the discoverer of the intracellular morphology of epidemic hemorrhagic fever virus, and one of the founders of the Chinese Society of Electron Microscopy which he used extensively in his virus morphology work. He also had extensively studied chlamydia. [b.11]


Academician Hong Tao, 72 at the time

However recently his prestige had got rather badly damaged.

At the beginning of the 2003 SARS epidemic that started in Guangdong province, on the 13th Feb 2003 precisely, Guangzhou Nanfang Hospital (on the SARS battlefront) issued an autopsy report of a SARS victim, stating that the cause of death was “viral pneumonia.” [b200]

At that very same time Hong Tao and an assistant at the Institute of Virology in Beijing were finding chlamydia particles from lungs tissues of two SARS victims, through electron microscopy.

On the 18th Feb the Institute of Virology of the Chinese Center for Disease Research announced that the main pathogen of atypical pneumonia in Guangdong was likely to be chlamydia. [b.203, b.103]

In the afternoon of the same day, the Guangdong Provincial Department of Health held an emergency meeting. The expert group headed by Zhong Nanshan, a member of the Chinese Academy of Engineering (whose attitude and work during SARS would be exemplary) believed that chlamydia cannot be simply identified as the only pathogen and railed against the limitations of the electron microscope approach.

In effect Hong Tao had made a basic mistake by ignoring the golden rule of infectious disease pathogen identification: Koch’s postulates. More precisely he actually ignored 3 of the 4 Koch’s postulates — quite a feat for an academician. [b501]

“If it is chlamydia, I will cut off my head and give it to you… .”

-- Dr Cai Weiping of the Guangdong expert group , from his hospital bed, after being infected while treating SARS patients [b102]

Both Hong Tao and Zhong Nanshan were members of the elite Chinese Academy of Engineering, but Hong Tao was more senior, based in Beijing, had been in the CCP army back in 49 (very important for connections) and was working for the CDC not for some hospital in the province. Hence the Chlamydia hypothesis became the official theory in China for a while, and totally ineffective antibiotics treatments were formulated accordingly.

While the world scientific community raced ahead, Chinese researchers who disagreed with Dr. Hong couldn’t get their hands on tissue, blood and serum samples from SARS patients.

On March 17–18 the CDC and the Ministry of Health held a first national joint meeting of SARS experts. At that meeting China’s CDC was designated as the country’s leading institution for SARS scientific research, taking the lead back forcefully:

“No unit or individual is allowed to publish research results in any form, including articles; if you want to publish, you must first report to the China CDC.” [b200]

Incapacitated by that incorrect official theory, Chinese scientists could not publish a single descent paper on the origins of SARS at that time [b301]. In particular it would later emerge that:

• Nanfang Hospital (Guangzhou) had found virus particles in lung tissue samples of SARS patients through electron microscopy as early as February 20, but their research was forced to stop after the “ban” issued at the meeting of the 17–18 March [b200]

• Researchers from the Chinese Academy of Military Medical Sciences (Beijing) also discovered virus particles in samples on February 26, which were identified as a coronavirus after being reviewed by 6 virus morphologists. On March 21, the Military Medical College reported to the relevant departments the discovery of the coronavirus. However, the findings were not officially announced until April 9. [b200, b103]

Eventually the Chlamydia theory was proven wrong by scientists abroad (mostly US and HK), by the beginning of April it was clear that a coronavirus was the cause of SARS.

Defying that trend on the 1st Apr 2003, Hong Tao and 20 other Chinese scientists published a paper defending the Chlamydia hypothesis [b207]. Nevertheless on the 3rd April 2003 the WHO declared SARS to be likely caused by a coronavirus [b.510], and on the 16th April 2003 it confirmed it to be the cause. [b509]

Even after the 16th April, an undeterred Hong Tao would tell reporters:

“It does not mean that this virus is the only culprit. [..] We cannot be sure that chlamydia is an important cause of death for patients, but according to our research on previous cases, the coronavirus alone is not so serious.” [b.203]

Academician Zhong Nanshan, 66 at the time

[admin]

Part 2 of 3

3.4 Fighting back with more P3s doing SARS research

Prior to the SARS epidemic, in 2002 (as part of the important reforms of the CDC in January of that year), Hong Tao’s Virus Morphology and Viral Diarrhoea Laboratory (病毒形态学与腹泻病毒实验室) at the CDC Institute of Virology was divided into three laboratories, all under his control: the prion (which can cause mad cow disease) laboratory department, the viral diarrhoea laboratory and Hong Tao’s laboratory, designated as the Academician Laboratory (each of the 5 Academicians at the Institute traditionally have their own laboratory). [b.3, b.8]

As discussed above, Hong Tao had recently lost quite a bit of credibility in the “Chlamydia Incident” (“衣原体事件”). After that sorry episode, it was reported that Hong Tao did not go to work at the Institute of Virology often, but concentrated on books at home. Nevertheless he still had a voice on investment matters and reviewed work (as should be expected of any Chinese academician).

Under Hong Tao the CDC had 3 P3 labs. One was supposed to be working on SARS, but what if these 3 laboratories could be made to work on SARS? Then Hong Tao and the CDC could carve themselves a leading role again in SARS research.

Let’s remember that at the beginning of 2004 the number of P3 labs in the country was still very limited, at around 15 to 20. Because of security concerns [b.4], the few SARS virus specimens that were necessary for experiments had become a “scarce resource” and were available only at the 6 designated storage institutions — which included the Institute of Virology [b.1]. So in effect very few P3 labs in the country could do SARS research on un-attenuated live strains, and with a bit of administrative flexibility three of them could be right under Hung Tao at the Institute.

Wang Jianwei (王健伟) who until then as an associate researcher at the Institute became the director of the viral diarrhoea department around Sep 2008. He was a former doctoral student of Academician Hong Tao and as an assistant, he was the one who with Hong Tao first discovered chlamydia in the lung tissues of deceased SARS patients. [b.3]

From his narrow field of viral diarrhoea Wang Jianwei could soon move to research on the much more critical SARS virus, with the encouragement of Hong Tao:

“Wang Jianwei is my student and I have the responsibility of teaching. SARS still has too many mysteries.”

-- Hong Tao, explaining his work on SARS after the Chlamydia Incident [b.3]

As one Chinese article would soon put it:

This relation between Hong Tao and Wang Jianwei explains exactly why post-doctoral students in the diarrhoea virus lab could do “interdisciplinary research on SARS virus” and select SARS as a major. For young researchers, the mysterious SARS virus is not only a severe challenge, but also a rare opportunity. [b.3]

The source above [b.3] goes on by reporting an official description of these students as having no weekends and holidays, no day and night, and sometimes even working overnight in the BSL-3. Good traditional party-speak, but not actually the best advertisement for lab-safety if one thinks of it.

As a result of this ‘interdisciplinary research’ approach, while the virus emergency technology department and the virus resource centre department were technically responsible for the preservation of SARS strains, some SARS strains and potentially infectious materials were also kept in the diarrhoea virus and in the prion virus laboratories.

3.5 Lab contamination — Feb 2004

Ren Xiaoli (任 小 莉, pseudonym) is a Virus Morphology doctoral student at the Institute of Virology in his last year before graduation. Under the guidance of Hong Tao (founder of the Chinese Virus Morphology discipline) and Wang Jianwei (王健伟), then director of the Viral Diarrhoea Department of the Institute of Virology, Ren Xiaoli and 21 doctoral and master students such as Yang (杨某) and Guo (郭某) joined the frontline of SARS scientific research. [b.3]

To understand exactly what happened we need to understand the layout of the rooms accessible to the viral diarrhoea department members. Unfortunately the official reports are very opaque and somewhat confusing as to these essential aspects. Fortunately some key insights were provided by insiders to reporters of Caijing and Southern Weekly [b.15]. Without these it would be impossible to make any sense of the limited official reports.

The viral diarrhoea department rooms seem to have been divided between P3 rooms and ‘normal’ rooms (possibly BSL2 [b505]). In particular one of the ordinary rooms held an electron microscope, a large apparatus that was the favourite investigation tool of Hong Tao and of his doctoral students.

Rooms 106 and 107 (on the first floor of the main building of the Institute of Virology) were mentioned by insiders. Presumably one room was the P3 laboratory, while the other one next door was a P2 electron microscope room.[b.1]

A professor in the Department of Medicine at Peking University, who has repeatedly entered the China Center for Disease Control, told reporters that the management of the virus has not been strict enough. For example, the strain was originally required to be stored in a special safe in the laboratory, and locked, but at some stage the SARS strain was placed outside in the corridor, because the overcrowding of laboratory personnel was very serious. According to his estimate, the number of laboratory staff at that time was three times the reasonable load of the laboratory. [b.4]

‘because the room was too crowded, the refrigerator containing the SARS virus was moved into into the aisle.’ [b.3]

In other words because the (likely newly established) P3 lab room of the viral diarrhoea department was too crowded, the samples fridge of the diarrhoea room was moved into the corridor, by the entrances to the 106 and 107 rooms. Consistent with improvised security measures to keep that fridge safe despite having it standing in a corridor, we are further told that

‘there is a padlock on the refrigerator door, and the key is kept by two people. To be on the safe side, a seal was also affixed to the refrigerator.’ [b.1]

This interpretation is in line with one of the first notices issued by WHO when responding to the leak accident:

’investigators have serious concerns about biosafety procedures at the Institute — including how and where procedures using SARS coronavirus were carried out, and how and where SARS coronavirus samples were stored.’

-- WHO, May 18 [b503]

After the Spring Festival holidays in 2004, Ren Xiaoli regularly took out the kit containing the normally attenuated SARS virus from the phosphate PH buffer solution in the fridge belonging to the P3 viral diarrhoea lab (but standing in the corridor) and directly walked into the ordinary Electron Microscope room next door [b.3], as she needed to use the electron microscope equipment there — a typical pathogen investigative approach of Hong Tao’s students.

Some report states that Ren actually prepared the deactivation solution [b508]— but being a student the method itself would likely have been decided by a superior.

She never thought that the dangerous virus in her hand might still survive. Indeed, According to previous experience a solution formulation composed of detergents such as phosphate buffer and sodium lauryl sulfate can deactivate the active protein of the virus. However the SARS virus inactivation technology adopted by the viral diarrhoea department had not been effectively verified and it was not included in the SARS virus inactivation program recommended by the Ministry of Health.[b.3]

Unfortunately this would cause a contamination of the ordinary electron microscope room. Ren and Cui (a virus morphology student in the viral diarrhoea department) developed symptoms such as diarrhoea and high fever as early as the 8th February 2004 [b.1, b.8], and went to Union Hospital and Friendship Hospital successively. Fortunately, their condition improved later and they did not infect anybody. [b.3]


‘There are two more infected people’ — Caijing, May 2004 [b.1]

At this point we must note that Ren and Cui cases only publicly emerged when they were found to be positive for IgG and IgM SARS antibodies in May 2004 [b.1], during the investigation triggered by the April LAI when all employees were tested.

China only succinctly mentioned their cases and the role they played in early July 2004 [b58], so about 2 months after they were first disclosed by Caijing. Shortly after that short official mention, an investigation by Southern Weekly [b.3] added more details obtained from insiders.

That’s all the information that was ever available on these two cases — despite them being essential for the rest of the story, and the names are pseudonyms.. Additionally these two crucial cases will not be included in the final Chinese report [b51]. Nor would the WHO ever mention them at the time [b501], thus mirroring the Chinese report.

In the end it is not clear whether the Institute of Virology itself actually knew about these cases before May when the Ministry of Health organized some systematic antibodies testing, but the question may be worth asking especially since these two researchers checked into some hospitals.

3.6 Community Transmission — Apr 2004

On March 7th Song (宋某 as given in the reports at the time), a 26 year-old graduate student of Anhui Medical University (安徽医科) started a short-term internship in the viral diarrhoea department of the Institute of Virology in Beijing, during which time she worked with adenovirus (腺病毒) and syncytial virus (合胞病毒). Her research has nothing to do with SARS. With her qualifications, she was not allowed to enter the P3 laboratory for SARS research and she always maintained that she never did. [b.1, b.4]

On the evening of March 23, she took the train back to Hefei (合肥, her hometown, a 1,000km train journey). On March 25, she felt body aches, fever, and physical discomfort, she took cold medicine and antibiotics by herself, but her symptoms did not alleviate. She returned to Beijing by train on March 27, and went for a consultation at Beijing Jian Gong Hospital (健宫医院) on March 29 where she was admitted for pneumonia. [b.1]

Inadvertently, she has been infected with the SARS virus.

Her mother Wei (魏某) came over to Beijing from Anhui on Mar 31 to be with her and if possible bring her back home. On April 2, Song and her mother returned to Hefei Huainan (Anhui) by train where Song was transferred to the Second Hospital of Huainan Mine (淮南矿二院). According to Caijing, the Virus Institute did not doubt Song’s symptoms at the time, but “later her mother took her to Anhui” and the Institute did not continue to investigate [b.1].

“She was actually very poor [ — ]. Sometimes I even recalled the way she was lying on the hospital bed, her fever was terrible, the expression on her face and the pain in her eyes. But I just feel that she was too stubborn and did not cooperate with our treatment, saying that she was going back to Anhui to continue treatment.”

-- Nurse Li, to a reporter [b.6]

On April 4, Song was further transferred to the First Affiliated Hospital of Anhui Medical University (安徽医科大学附属第一医院) for viral pneumonia to continue treatment.

On April 8, Song’s mother, Wei, who had now been with her for 8 days, began to develop fever and was admitted to the First Affiliated Hospital of Anhui Medical University with unexplained viral pneumonia. On April 19, Wei’s condition suddenly worsened and despite efforts to save her she died (community case #1). After receiving the report, the local health department immediately activated the SARS early warning mechanism. [b502]

Since she had never been exposed to this deadly virus, Song did not receive any warning. Even after the death of her mother, Song did not think of the word “SARS”. From beginning to end, Song never suspected that he was infected with the SARS virus.

“I have never been to a laboratory that stores the SARS virus.”

“I still don’t know when and where I was infected with the terrible SARS virus”

-- As told by Song [b.2, b.14]

At Beijing Jiang Gong Hospital a 20y old nurse named Li (李某), whose job was to take care of fever patients not yet examined, had been in contact with Song [b.6]. On April 5, nurse Li began to experience chills while waiting for a bus. On Apr 7, she developed fever, cough and other symptoms, and was admitted to Jian Gong Hospital.

Because her condition did not improve after treatment, she was transferred to the intensive care unit of Peking University People’s Hospital (北京大学人⺠医院) on the 14th. She first learnt that she had contracted SARS on the 21st April. [b.1]

Song was not the only primary case. Yang, a postdoctoral fellow at the institute [b502], fell ill after working in the viral diarrhoea department. He was hospitalized 23 days after Song (17th April) and then put in isolation on the 22nd April on confirmation of the SARS diagnostic.

3.7 The Response of the Authorities

China officially reported Li SARS case on the 22nd April, then Song, Wei and Yang SARS cases on the 23nd April [b502, b504]. The institute was temporarily closed and quarantined on the 23rd April. [b1, b513]


Staff of the Chinese Center for Disease Control and Prevention closing the gate of the Institute of Virology, preparing for terminal disinfection , 100 Yingxin Street [b.3]

An additional case was reported on the 28th April, a 49y old female retired doctor who on the 12th April was in the same hospital ward as nurse Li. In total Li was linked to 5 confirmed cases. [b.7]

During the 2003 outbreak, the transmission of SARS was greatly amplified in hospital settings. As a risk reduction strategy all seven Beijing SARS cases were eventually treated in one selected hospital, Ditan Hospital (with Song being eventually treated in Anhui).

Nevertheless the patients were initially treated or assessed in open wards at seven hospitals (five in Beijing and 2 in Anhui) before suspicions of SARS were raised and procedures of isolation and infection control were introduced. In addition, the two patients in Anhui travelled long distances within China by train. As these events created opportunities for multiple exposures, Chinese authorities undertook extensive tracing and follow-up of contacts.

By the end of April, 700 people were medically quarantined. More than 260 people from the Institute of Virology, including scientific researchers, graduate students and their family members, were quarantined or dispersed, with 24 people being sent to the Beijing Chest Hospital. In the town of Xiaotangshan, Changping District, a resort received 145 people. [b1]

In total nearly 1,000 people would be quarantined (a figure never released by the Chinese CDC). [b106]


Supplies arrive for staff under quarantine of the National Institute of Virology in Beijing, China, 30 April 2004. A laboratory at the institute is thought to be the source of the recent SARS outbreak.
100 Yingxin Street, Source: WHO [t.21]

Two additional confirmed cases of SARS and three additional suspected cases were reported in Beijing on 1 May, all related to the Viral Diarrhoea Department of the CDC’s National Institute of Virology in Beijing.

“The cases had been linked to experiments using live and inactive SARS coronavirus in the CDC’s virology and diarrhoea institutes where interdisciplinary research on the SARS virus was conducted.”

-- China Daily, [b.59]

On 2 May, China announced the three suspected cases as genuine cases of SARS, bringing the total cases in a recent outbreak to nine. 189 people were released from quarantine.

On 18 May, after no new infections had been reported in a three-week period, WHO declared that that ‘China’s latest SARS outbreak has been contained, but biosafety concerns remain”. [b503]

On May 21, Zhang, the last SARS case in Beijing, was discharged from Beijing Ditan Hospital.

On May 23, all 747 close contacts in Beijing were lifted from quarantine, the treatment of SARS patients in Beijing and Anhui ended and the SARS transmission chain was considered as stopped. [b.54]

3.8 Summary of cases:

There were in total 11 cases over four generations. Note that the official report would only mention the 9 cases of the Song-contamination chain (April), ignoring the two February primary cases that are linked to the contamination of the diarrhoea lab and had been disclosed by Caijing since May. [b512, b513, b514]

a. February Lab contamination: 2 primary cases:

Ren (pseudonym) and Cui were found positive for antibodies in May. According to the official report Ren caused the contamination of the Viral diarrhoea department by taking the un-attenuated SARS virus from the sample fridge lab for observations under electron microscope. Little is known about Cui beyond the fact that he worked in the viral diarrhoea department. It was established that he contracted SARS not from Ren but independently, making him another primary case.

For some reason, neither Ren or Cui are included in the list of patients in the official investigation and WHO reports at the time — which instead focuses on the April outbreak. They will eventually be mentioned by the WHO in [i.1].

Given that these two cases ended up in hospital it is rather likely that they raised an alert and that the LAIs were detected at the time, and not after the blanket IgG testing of staff and students following the April outbreak. The cover-up by the Chinese authorities of these two early cases, which persisted even after the April outbreak, can then be explained by the rather unsavoury reasons for the contamination of the institution.

When eventually forced to publicly deal with the April outbreak, the Chinese were then careful not to ever mention these key February cases, leaving the reason for the April outbreak officially unresolved when that reason was by then well known (and even leaked to Caijing).

b. April events: 1st generation: 2 primary cases from contaminated lab

Song (宋某), a 26-year-old female postgraduate student from Anhui Province. She had started an internship in the viral diarrhoea department on the 7th Mar. She did not return after the 22nd March as she soon fell ill.

Yang, a 31-year-old male post-doc researcher at the same virology institute who was hospitalized on the 17 April, got independently infected. Indeed he started developing symptoms about 15 days after he last met Song, briefly in a corridor of the Institute, when the incubation period of SARS is 2 to 10 days. [b7, b516]

c. April events: 2nd generation.

The two cases in the second generation are both linked to close personal contact with the postgraduate student. These cases are her 53-year-old mother, Wei (魏某). The second case is a 20-year-old nurse in Beijing, Li (李某), who treated the postgraduate student, from 29 March to 2 April, during her initial hospitalization in Beijing.[b.7]

d. April events: 3rd generation.

Five further cases have all been linked to close contact with the nurse. Three are relatives: her 45-year-old father, her 44-year-old mother, and a 36-year-old aunt who visited her in hospital [b515, b.7]. The fourth case linked to the nurse is a 49-year-old retired female doctor who was admitted to hospital because of another illness and shared a room with the nurse. The retired doctor’s 23-year-old daughter-in-law, who accompanied her at the time of hospital admission, is the fifth case. [b.6]


Extract from Investigation Report — note that there were 2 additional Feb cases (11 in total) [b.57]

3.9 The Official Investigation

a. Brief role of the WHO and missing February cases

The WHO sent a team on the 26th April 2004 which included ‘experts in epidemiology, virology, infection control, and laboratory biosafety’ [b518].

It seems that the WHO team was supposed to second the Chinese investigative team, not to do its own independent investigation:

‘On April 23, the Ministry of Health established an expert group composed of the Academy of Military Medical Sciences, Beijing Centers for Disease Control and Prevention, and China Centers for Disease Control and Prevention on infectious diseases to conduct a special investigation on the source of infection in this SARS case. WHO sent experts to participate in the investigation.’ [b519]

On the 12th May, that expert group formed an investigation team composed of 7 experts from the Academy of Military Medical Sciences, Beijing Municipal Center for Disease Control and Prevention, and CDC Institute for Infectious Disease Control and Prevention was formed. [b.1, b.3]

This China-WHO team conducted a thorough review of the April cases (but not of the February ones who were officially discovered sometime in May via systematic IgG testing of lab workers [b1]):

‘The investigation team conducted epidemiological investigations on the two [April] cases, interviewed all the staff in the same laboratory, conducted on-site investigation and sampling of the virus, and handed the collected samples to two national-level laboratories and one. The WHO network laboratory conducted tests according to a unified technical plan. As of May 11, the expert team has not yet determined the source of the infection.’ [b519]

Note that ‘the expert team has not yet determined the source of the infection’ is disingenuous. First it had been established by that time that it was a case of lab contamination [b518], so really what is meant is that the precise source of the lab contamination is still unknown. Secondly, understanding the source of the contamination requires looking into the two February cases identified by testing in May — which the Investigation team was not doing.

‘Results of investigations to date point to laboratory research at the National Institute of Virology in Beijing as the likely source of the outbreak. The institute has been engaged in research with the SARS coronavirus, including the development of a vaccine’. [b518]

On May 14, it was learned from the representative office of the World Health Organization in China that the investigation team had confirmed that the SARS epidemic originated from a laboratory infection at the Viral Disease Control and Prevention Institute of the Chinese Center for Disease Control and Prevention (CDC), but the investigation team still did not clarify the details.

On May 21, Caijing published the first article in the Chinese press [b1] mentioning the lab escape and the early February cases. Hence the Chinese side was actually aware of these early cases at the very latest by the 21st, probably some days before.

The last WHO update was on the 18th May 2004. No update followed and no WHO report was released. The investigation was effectively to be managed by China.


World Health Organization. Emergencies preparedness, response. Situation Updates -- SARS
Source: WHO [b520]

b. The Official Conclusions

The Ministry of Health would produce its investigation report on the 1st July 2004. There is no mention of the WHO at the time in the press reports. The WHO team had most likely long left the scene and its role in the investigation, whatever its extent, was not discussed.

The Ministry of Health would produce its investigation report on the 1st July 2004 [b51], under the title ‘Analysis Report on the Epidemic Control of the ‘4.22’ SARS Epidemic in Beijing in 2004' (2004年北京‘4·22’SARS疫情流行控制情况分析报告).

The report covers the nine April cases starting with Song. It briefly mentions Ren & Cui by stating that they had tested positive to IgG and IgM antibodies but does not include them with the nine April cases and does not mention that their cases go back to early February. [b58]


Summary of the 9 cases starting from Song [b.7]

The investigation pointed out the six major problems of “illegal working procedures”: [b100, b58]

First, research projects are interdisciplinary. The viral diarrhoea department researches the gastrointestinal virus field, but has undertaken SARS research projects as a cross-disciplinary topic. The staff are not familiar with the topic, which has caused safety risks.

Second, safety management is not paid attention to. The staff adopted a new method of inactivation, without the academic committee’s validation, which scientific basis was insufficient, and the department director approved it without authorization. The inactivation effect had not been strictly verified, and there is no verification plan, record and content.

Third, technical operations are not conform to the standard, as per the absence of safety precautions in ordinary laboratory operation, thus violating the regulations of the Ministry of Health that the inactivation of SARS virus must be carried out in a laboratory with a biosafety level above P2 or in a biological safety cabinet.

Fourth, the staffing is not strict. A large number of graduate students and fellows who lack professional knowledge are used for high-risk research, and there is no strict biosafety knowledge training for relevant personnel.

Fifth, health monitoring is not in place, it violates the laboratory personnel health monitoring system, accident reporting system and other regulations formulated by the Ministry of Health, failed to promptly report abnormal conditions such as multiple fevers of laboratory personnel, and failed to take necessary measures. Two of the laboratory staff developed fever, and one was hospitalized for two weeks, without attention being paid to the cases and no reporting was made.

Sixth, the implementation of the system was not serious and violated the rules of the Ministry of Health and other four ministries regarding the implementation of two-person access to the P3 laboratory, as single-person operations occurred many times.

Official conclusions 2 Jul 2004, [b58]

Investigative journalists add important elements

Over about two months a few Chinese magazines and newspapers were able to add some crucial elements of this story (some acquired via insiders), such as the positive cases of Cui and Ren [b1] and the location of the fridge out of the P3 lab [b3].

3.10 The omissions

Some international experts were disappointed that many details about the incident and the lab’s operating procedures remain very opaque or simply hidden.

“I was hoping for a full, more open account of what happened,”

-- Antony Della-Porta, the Australian biosafety expert who led the earlier WHO investigations of the SARS escapes in Singapore and Taiwan, but not Beijing. [b508]

a. No full report published

This was supposed to be a joint China-WHO investigation [b519].
However the WHO simply withdrew from the scene without trace. There was not even an update posted by the WHO after the 18th May and the WHO did not publish the official report produced by China.

China itself only made public a few brief extracts on the 1st July 2004 (extracts which do not mention the WHO). It never published the full report.

b. February inspection of the Institute

On July 12th, 2004, shortly after the reorganisation meeting, according to media reports at the time, the Ministry of Health was rather sanguine about the SARS virus leak. And they had good reasons.

The investigation report obtained by some reporters indicated that in February of that year (2004), following the the new SARS-samples handling protocol issue by the WHO on the 18th Dec 2003, the leaders of the Ministry of Health went to the Chinese Center for Disease Control and Prevention to inspect the P3 laboratory of the Institute of Virology and found problems with it. They asked the CDC to propose a rectification plan and a plan to provide financial support, but the CDC did not implement it seriously. [b106]

Possibly the inspection was just part of the Ministry review of P3 labs triggered by the new WHO guidelines following the Taiwan lab escape — however most P3 labs are understood to have been visited at the very end of December 2003 or early in January. Alternatively it may have been triggered by the two suspected cases of SARS (Ren and Cui) who ended up in hospital in February.
Whatever the reason, the Ministry of Health and the Chinese Center for Disease Control and Prevention knew of some issues at the laboratory back in February.

c. The cause of the contamination

Ren and Cui had tested positive for antigens back in May, as disclosed by Caijing [b1]. Judging from the few available extracts, the Ministry of Health report simply confirms the positive tests but never mentions the February context, nor does it include them in the official count of the cases (hence stopping at 9 and not 11).

In any case the official name clearly focuses on the April chain of contamination (“‘4.22’ SARS Epidemic in Beijing in 2004”) [b51] so implicitly dropping the early February cases.

As mentioned above, the purpose of this sleight-of-hand was most likely to avoid having to disclose the rather unsavoury reasons of the contaminations at the institute.

3.11 The sanctions:

The Ministry of Health decided the following sanctions: [b4]

Ruan Li (阮力), director of the Virus Disease Control Institute who has the main leadership responsibility, Dong Xiaoping (董小平), deputy director of the Institute, and Wang Jianwei (王健伟), director of the Viral Diarrhoea Department, received administrative sanctions. [b4]

Li Liming (李立明), the director of the Chinese Center for Disease Control and Prevention was given administrative demerits and resigned.[b4]

“Neither Taiwan nor Singapore’s laboratory infections caused second-generation cases, but this time our SARS incident not only caused transmission, but also third-generation cases. This is our failure to do a good job. Sorry to the government and people. We don’t have any excuse on the issue.”

-- Li Liming, May 8 2004, at a reorganization meeting held by the Institute of Virology

Yang Xiaoguang (杨晓光), his deputy director, who had important management responsibilities, was given major demerits and resigned. [b.4]

As for the student behind the pseudonym of Ren Xiaoli, we are told that s/he was not punished, being only a student and not directly responsible. This seems a bit odd and some questions are worth asking about the true identity of that person — given as the main proximal cause of the contamination of the lab — if the story concerning that person is true indeed.

Academician Hong Tao, director of the Institute, was not sanctioned. This triggered some rather vitriolic analysis of the nepotism of the Chinese scientific institutions:

“The academician system has also set an example for new academics in China: Those who work hard and do research are idiots, and those who can get nothing, or get more with less, are ‘brilliant people with leadership skills’.”

-- Yi Ming, The problems of Chinese academia and their way out (亦明, 中国学术界的问题及其出路), Jul 2004 [b301]

3.12 All is well that ends well:

In any case the sanctions seem to have been more on paper than anything else:

Wang Jianwei (王健伟) CV states that he worked at the Institute until Feb 2006, then moved to be director of Merieux Laboratory in Beijing, He is today the director of the Chinese Academy of Medical Sciences & Beijing Union Medical College. He also served as a member of the Standing Committee of the Party Committee. Last, he was appointed executive editor of Biosafety & Health magazine [b303] and has produced a manual on laboratory biosafety. [b304]



Wang Jianwei

Dong Xiaoping (董小平), saw his job his job description change from ‘Director of the Prion Division, Deputy Director, Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention’ to ‘Director of the Prion Department, Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention’ — so basically dropping the ‘deputy director’ title. In 2012 he would reclaim that full title and is still in the same position. He enjoys special allowances from the State Council and is a member of the CPPCC National Committee (China top political advisory body).

He is also the deputy director of the State Key Laboratory of Infectious Disease Prevention and Control and the director of the Prion Department of the Viral Diseases Institute. He is also a member and chief reviewer of the Biosafety Professional Committee of the National Accreditation Committee of Chinese Laboratories and finally he is co — Director of the Chinese CDC.


Dong Xiaoping

In February 2020 he became an expert of the “WHO-China Coronavirus Disease Joint Expert Investigation Group” and was part of the February 2020 joint-mission. [b305]


Report of the WHO-China Joint Mission on Coronavirus Disease 2019–16–24 Feb 2020

Li Liming (李立明) would later serve as Party Secretary and Executive Vice President of Beijing Association Medical. He is a professor at the Peking University School of Public Health.


Li Liming

Ruan Li is still a professor of the Institute of Virology.

Hong Tao is still a well respected academician and enjoys special allowances from the State Council.

In 2016, Hong Tao, Wang Jianwei and Song Jingdong published the ‘Medical Virus Atlas’, compiled from nearly 50,000 electron microscope images of viruses.

In 2019 Hong Tao received a commemorative medal for the Celebration of the 70th Anniversary of the Founding of the People’s Republic of China, mentioning his significant contribution to the cause of medical virology and infectious disease prevention and control in China. [b306]

On the 7th Jan 2020, his student Song Jingdong (宋敬东), associate researcher at the Institute, took the first ever Electronic Microscope picture of SARS-CoV-2.


Novel Coronavirus Wuhan Strain 01 (IVDC China’s CDC)

3.13 Déjà vu:

On the 5th August 2021 US Right To Know released some emails showing that some senior researcher got infected with SARS-CoV-2 at the very same Beijing Institute of Virology (NIVDC) in January or February 2020:

The SARS-CoV-2 lab-acquired infection came to light in a set of emails dated Feb 14, 2020, between virologists Shan-Lu Liu (Ohio State University), Lishan Su (then of the University of North Carolina) and Shan Lu (University of Massachusetts Medical School).

Shan-Lu Liu noted that his former director at NIVDC “has now been infected with SARS-CoV-2”, and in a separate email acknowledged that his former colleague “was infected in the lab!”

There is a particular irony in the fact that this information was disclosed while Shan-Lu and Lishan were working on a commentary which very purpose was to refute the possibility that SARS-CoV-2 may be a research related accident!

The context of the email exchange was in the preparation of a commentary to refute the hypothesis that the novel coronavirus SARS-CoV-2 came from a lab, which Shan Lu had solicited as editor-in-chief of Emerging Microbes & Infections (EMI), a China-linked journal.

While there was no official reporting of that LAI, at least Shan-Lu recognised the fundamental issue, which is effectively a repeat of the 2004 SARS-1 leaks:

Shan Lu responded, “I actually am very concerned for the possibility of SARS-2 infection by lab people. It is much more contagious than SARS-1. Now every lab is interested in get[ting] a vial of virus to do drug discovery. This can potentially [be] a big issue.”

[admin]

Part 3 of 3

4. Conclusion: Lessons from SARS Lab-Escapes

4.1 Importance of people and processes:

All the three SARS lab-leaks that we looked at were the result of people either making mistakes or taking deliberate short-cuts, and were often made worse by bad processes that only surfaced after the investigation and were not questioned before — even when seemingly quite obvious to an external observer.

It is therefore important to remember that a P3 or P4 certification is largely secondary in terms of biosafety. The major risk factors are the people entering the lab and the processes that are applied there. It is thus very easy to build a P3 but practically run it as a P2 as far as people and processes are involved, a point that the 2004 Beijing SARS lab leaks amply illustrated.

Compared to other industries, such as nuclear industries for instance, the situation is worse. People working in nuclear power stations typically go through lengthy qualifications. Also a radioactive exposure or increased coolant temperature can usually be immediately detected and measured via sensors. In contrast biological P3 labs often see students with limited qualification in biosafety working there (see Singapore and Beijing leaks), and pathogen exposure is typically not detected until too late. The parallel would thus be a nuclear power station where students are routinely given a chance to manipulate radioactive fuel, or put in charge of reactor controls with limited oversight and limited sensors — all after a short risk induction.

In the extreme a P3 or P4 designation may actually be counterproductive if it leads to a false sense of safety. This was actually very well understood by some Chinese experts straight after the Singapore Lab-leak:

“Hidden non-hardware dangers of P3 laboratory

While the World Health Organization puts the emphasis on the P3 biosafety level, many experts interviewed believe that P3 classification is only one aspect of laboratory safety control. Compared with the laboratory’s hardware facilities, processes (software) and management issues are more important.

According to Professor Zhu Qingyu, a P3 laboratory only means that the laboratory meets the standards in terms of physical protection. In fact, in terms of laboratory safety, the human factor comes first. “(Scientific research personnel) do not have good quality and sense of responsibility, (scientific research institutions) do not have strict and perfect management, and P3 laboratory alone will not work.” Zhu Qingyu said.

WHO warns of hidden dangers in laboratories. Are the nation’s SARS laboratories safe? Oct 2003, Oriental Morning Post — a prophetic article before the Beijing SARS leaks.

“Safety is no small matter. A safety breach may occur anywhere.” Gao Fu, an academician of the Chinese Academy of Sciences and deputy director of the Chinese Center for Disease Control and Prevention, said of the accident, “the string of biosafety cannot be relaxed for a moment.”

-- China Science News (2014–07–25 14th Edition)

A consistent and systematic training is effectively the cornerstone of a lab biosafety,

“These narratives of escaped pathogens have common themes. There are unrecognized technical flaws in standard biocontainment [ — ].The first infection, or index case, happens in a person not working directly with the pathogen that infects him or her, as in the smallpox and SARS escapes. Poor training of personnel and slack oversight of laboratory procedures negate policy efforts by national and international bodies to achieve biosecurity [ — ].”

-- Martin Furmanski in the Bulletin of the Atomic Scientists, Mar 2014

As to whether this state of affair can ever be fully rectified given human nature, some experts such as Martin Furmanski remain skeptical:

Looking at the problem pragmatically, the question is not if such escapes will result in a major civilian outbreak, but rather what the pathogen will be and how such an escape may be contained, if indeed it can be contained at all.

-- Martin Furmanski in the Bulletin of the Atomic Scientists, Mar 2014

4.2 Importance of Laboratory location:

The location of major labs (P4s and top P3s), especially civilian ones, tend to be often in major cities — close to universities and related biological industries — and thus often in the middle of land and air transport hubs, including international transports.

While the advantages of such locations in terms of research and industries are obvious, these locations may also dramatically enhance the risk of a lab breakout being able to move from an undetected limited spread — where the pathogen may die out without having the time or the occasion (location/optimal host) to adapt — to a full blown epidemic and even pandemic.

The Taiwan and Beijing lab leaks offered some prime examples. In the case of Taiwan the infected individual flew to Singapore the day after getting infected (so not infectious yet) and then flew back to Taiwan when potentially infectious. Luckily nobody on his flight or in the conference he attended in Singapore got infected. In the case of Beijing one infected individual travelled back and forth by train three times between Beijing and Ahnui, triggering cases in these locations.

This location risk has been researched and simulated, providing interesting insights. For example Merler et al modelled the possible spread of a lab escape in various European urban settings (Rotterdam, London, Stockholm, Milan, Madrid and Paris) using an agent simulation and a range of R0. Their conclusion was that the location of the laboratory may play an essential factor in determining the risk of an outbreak based on a lab escape event:

For instance, given a BSL facility located in the UK, we found that the probability of epidemic outbreak when the pathogen is accidentally released from a hypothetical BSL laboratory in Wales (UK) may be three to five times lower than that estimated for a BSL laboratory in London if R0 <1.5. These differences are ascribable to differences in population density and sociodemographic structure [ — ].

-- “Containing the accidental laboratory escape of potential pandemic influenza viruses” (Nov 2013), Merler et al.

One of their conclusions was that escapes may lead to a cryptic local spread that simply dies out before even being detected. Hence it is quite possible that in a sparsely populated environment a lab escape may simply trigger an undetected local spread (not much different from a local zoonosis in a remote village), while having a good chance of triggering a full breakout in a much densely populated urban setting in close proximity to transport hubs.

Martin Furmanski additionally drew attention on the simultaneous development of increased pathogenicity studies, which have the potential of releasing a virus with a high R0 — another key risk factor:

Experiments that augment virulence and transmissibility of dangerous pathogens have been funded and performed, notably with the H5N1 avian influenza virus. The advisability of performing such experiments at all — particularly in laboratories placed at universities in heavily populated urban areas, where potentially exposed laboratory personnel are in daily contact with a multitude of susceptible and unaware citizens — is clearly in question.

If such manipulations should be allowed at all, it would seem prudent to conduct them in isolated laboratories where personnel are sequestered from the general public and must undergo a period of exit quarantine before re-entering civilian life. The historical record tells us it is not a matter of if but when ignoring such measures will cost health and even lives. Perhaps many lives.

-- Martin Furmanski in the Bulletin of the Atomic Scientists, Mar 2014

____________________________________

Box: Can lab processes ever be fool-proof?

Formal processes school:

One standard reaction when faced with human errors and faulty processes is to try to redesign processes and reinforce training. While this answer has some value, experience would indicate that in a domain where the human factor is very important — such as in P3 lab — such an approach may never work perfectly.

For instance:

• Adding more rules for those handling pathogens won’t help if the people infected are usually not the ones handling the pathogens (i.e: indirect infections via contamination of the lab surfaces, via aerosols or via wastes).
• Adding more federal and international regulations won’t help if the regulations aren’t consistently followed.
• If there are still unrecognized technical flaws in the standards for biocontainment, how would we know until an incident made those flaws apparent?

The main issue is that this response draws from a largely mechanical approach to risk which is better suited to industrial environments where (i) the hardware is the main risk factor and (ii) where the human actions are more predictable and standard; and (iii) the human factors do not routinely involve students and other lightly qualified personnel — but highly trained professional elements.

That mechanical approach to risk is also better adapted to an environment where the risk is better visualized: be it mechanical (machineries) or detectable (nuclear radiations, chemical vapours).

Another issue correctly pointed out by Lipsitch and Inglesby as well as others, is that the mechanical approach to risk may also produce incorrectly small evaluation of the risk involved, by ignoring ‘model risk’, the risk that the (often mechanical) model used to derive such risk evaluation is actually incorrect.

[ — ] when one performs a risk analysis and estimates an exceptionally low probability (P) of a catastrophic outcome, it is crucial to consider the probability q (which may exceed P) that the model used to derive that probability is itself wrong, in a way that understates the true probability of the outcome.

-- [Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited”, Lipsitch and Inglesby]

That largely mechanical approach was used in particular for the Risk and Benefit Analysis of Gain of Function Research (a simulation over event trees, with some inspiration from the nuclear power generation risk analysis and the military and civil aviation accident analysis).

Inherent safety school:

An alternative approach to risk is more pragmatic. Drawing on the recognition of the limitations of the human factor, that approach focuses instead on limiting the inherent risk factors.

• Limiting the work on enhanced pathogens (reducing the R0)

• Positioning labs in sparsely populated environments and far away from transport hubs

• Possibly implement practical quarantines in labs

See for instance ASM Letter ‘Assessing and Managing the Risks of Potential Pandemic Pathogen Research’ (Daniel Rozell).

An analogy:

Interestingly a similar problem was long at play in the world of finance, with a derivatives industry swearing by a mechanical approach to risk which was plagued with modelling failures, and fighting hard to remain lightly regulated. Until the events of 2007–08 that is; events which resulted in better regulation and a return to inherent safety principles (exchange traded derivatives vs. over-the-counter ones, higher provisioning requirement pushing for less inherent risk in the books of the banks, etc.).

That it took the near destruction of Western economies to remediate the problem is rather humbling.
_____________________________________

4.3 Importance of Institutional Factors:

The quality of the response to a Lab-Escape in a given country is largely framed by a few key institutional factors, as nicely demonstrated by the 2003–04 SARS lab-leaks:

1. Government (central and local) transparency

2. Central government willingness to learn from mistakes

3. Free press that can contribute to transparency

In particular we note that:

• The answer in Singapore was very strong on (1) and (2), much less on (3) where the press did not add any material knowledge.

• The answer in Taiwan was very strong on (2), a bit less on (1) most likely due to the military setting (a P3 lab with a military P4 lab), and rather strong on (3) [interestingly mainland China media reports also added some important details].

• The answer in Beijing was very poor on (1) and (2) but rather good on (3), as investigative journalism provided essential details without which we would have only the most limited understanding of the exact circumstances of the leaks, since neither the WHO or Beijing released any report.

Unfortunately SARS-CoV-2 outbreak would in due time provide an example where the government answer would be very poor on all three institutional factors.

“There is no one quick fix to the Chinese system to make it respond better next time,” said Hung [Ho-fung Hung, a professor in political economy at Johns Hopkins University in the US]. “But if there is one single factor that could increase the government’s responsiveness to this kind of crisis, [it would be] a free press.”

-- ‘What China’s empty new coronavirus hospitals say about its secretive system’, The Guardian, 12 Feb 2020.

4.4 Adapting Case Definitions to include potential Laboratory Exposure:

At the time of these SARS lab-escapes, the WHO and the US CDC used a definition for a ‘SARS suspected case’ that required that the case had one or more of the following exposures during the 10 days prior to onset of symptoms:

1. close contact with a person who is a suspect or probable case of SARS;

2. history of travel, to an area with recent local transmission of SARS;

3. residing in an area with recent local transmission of SARS.

Unfortunately an index case of a SARS Lab-escape would not meet any of these 3 criteria, potentially delaying the timely recognition and reporting of the case, as the ‘case definition’ feeds into the national early reporting systems. The ‘suspected case’ definition could thus make all the difference between an admission into an hospital with possible SARS symptoms being treated as a suspected SARS or not. This was a major problem.

In Apr 2004, in a review of the 2003 Singapore LAI published in the New England Journal of Medicine (NEJM), the authors stated that:

‘This case of laboratory-acquired SARS indicates that concern regarding the potential risk to laboratory personnel is justified, and the epidemiologic criteria in the current case definitions of the World Health Organization (WHO) and CDC may need to be amended to include laboratory exposure to SARS-CoV as a risk factor for infection.’

That proposal was a very reasonable one and was soon validated by the Beijing-Anhui LAIs that were detected that very April month of 2004.

While that case definition discussion only applied to SARS, its validity is much larger and a laboratory exposure (direct or via contacts) should frame the definitions of suspected cases for any pathogen known to be handled there.

4.5 Managing the risk of a new biotechnology age:

We are at the cusp of a new biotechnology age. As with any new technology age, we see competition between nations driving developments and implementations that quite often are running ahead of a proper risk assessment.

It took a few unfortunate accidents for the nuclear energy sector to develop safer practices and technologies, or for some countries to simply decide that the risk/benefit did not justify the technology (see the Atomausstieg). It also took some near-misses to see a dramatic reduction in ballistic missile headcounts.

The biotechnology age is not different. Without a constant risk/benefit assessment, erring on the conservative side if necessary, we will go through the same painful learning process as we did with the nuclear age.

Easier said than done for sure. First we are in a context of international competition to reap the benefit of these new technologies. Secondly, contrarily to nuclear applications, the technical entry ticket cost seems much lower, while the required human ticket cost (with qualified personnel) may sometimes not be not fully paid to cut corners. To make things worse the physical signature is much less obvious (about any non-descript urban building could contain a P2 or P3), and there is simply no international registry of P3s or even P4s.

This is not to say that all biotechnology work should be stopped. Not at all — this would be bad luddite advice and illusory. But what it means is that the risk framework should develop in tandem with the technology, not after, unless we want to repeat the same mistakes.

References

For a quick approximate translation of pages in Chinese, please use the Google Translate extension with Chrome. It works rather well.

It is fairly common for Chinese pages to be scrubbed from the internet. If you cannot find a page given in the references please try https://web.archive.org/. Most have been saved there. If one is still missing please let us know (via a comment to the article). We have kept copies and can put them online.

Introduction:

[i.1] WHO SARS Risk Assessment and Preparedness Framework, Oot 2004, http://www.who.int/csr/resources/public ... 2004_2.pdf

Singapore:

[s.1] ‘Laboratory-Acquired Severe Acute Respiratory Syndrome’, NEJM, Apr 2004, //www.nejm.org/doi/full/10.1056/NEJMoa032565
[s.2] ‘Recent Singapore SARS case a laboratory accident’, The Lancet, Nov 2003, https://doi.org/10.1016/S1473-3099(03)00815-6
[s.3] ‘Review of SARS virus leakage accidents in laboratory’, China Science News, Jul 2014, http://news.sciencenet.cn/htmlnews/2014/7/299630.shtm
[s.4] For the mention of the renovation works and mixed BSL-2/ BSL-3 activities: https://europepmc.org/article/med/14603886
[s.5] ‘International Consultant Della-Porta Challenges BSL-3 and BSL-4 Standards’ ://www.tradelineinc.com/reports/2004-9/international-consultant-della-porta-challenges-bsl-3-and-bsl-4-standards
[s.6] Details of 3 lab visits: https://www.publish.csiro.au/MA/pdf/MA08062
[s.7] 17th August: https://www.cidrap.umn.edu/news-perspec ... ig-concern
[s.8] Official investigation panel report — a must-read: ‘Biosafety and SARS Incident in Singapore September 2003’: https://www.nas.gov.sg/Farchivesonline/ ... 23-MOH.pdf

Taiwan:

[t.1] IPMR and Taiwan bio-warfare capabilities: https://bit.ly/3ldKkaU
[t.2] For a Chinese account of the purchase of the P4 from France (codenamed “White Chicken 16”), see ‘What about biosafety! Unpopular knowledge written on National Security Day’. Saved Chinese original: https://bit.ly/3n1ZMaw, saved approximate translation: https://bit.ly/2IhqTiU. The original may be accessed (unless purged from the internet) by clicking on the first link here: https://bit.ly/3kae1Is.
We note that [t.9] confirms that all Taiwan BSL3/4 prior to 2003 were foreign-made. See also [t.18] for a confirmation of advanced French equipment.
[t.3] For Anthony Della-Porta profile as internationally renowned expert in biosecurity, biocontainment and biological safety: http://www.bio2ic.com/about/tony-della-porta
[t.4] Long hours: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135754/
[t.5]. In a hurry: https//www.washingtonpost.com/archive/politics/2003/12/18/lab-rules-ignored-in-new-sars-case/91508154-b8dd-4ba3-a6f0-c7d002d28373/
[t.6] Many details: http://travelbanter.com/showthread.php?t=5501
[t.7] Bag: https://www.sunjournal.com/2003/12/21/o ... infection/
[t.8] ‘He put his head inside’: the (partial) LAI database maintained by the American Biological Safety Association (ABSA) has some details otherwise unavailable, https://my.absa.org/LAI (search with keyword SARS): ‘January 7, 2004. Report on the laboratory-acquired SARS Case in Taiwan, Previously available online: During a final lab clean-up, the investigator noted “leakage from the plastic bag in the negative-pressure transport chamber”. He could not reach the spot with the attached gloves, so he wore a “normal mask” and surgical gloves to disinfect the leakage with alcohol spray. However, even with the chamber door open, he could not reach the spill, so he put his head inside the pass-through to disinfect.’
[t.9] WHO investigation and international cooperation: ‘Development of Laboratory Biosafety Management: The Taiwan Experience’ https://www.liebertpub.com/doi/pdfplus/ ... 0701200104
[t.10] closure: https://www.nytimes.com/2003/09/24/worl ... -case.html
[t.11] ‘International Consultant Della-Porta Challenges BSL-3 and BSL-4 Standards’: http://www.tradelineinc.com/reports/200 ... -standards.
See also the excellent https://journals.sagepub.com/doi/pdf/10 ... 0601100406
[t.12] Disaster: https://www.newscientist.com/article/dn ... rs-in-lab/
[t.13] Taiwan Epidemiology Bulletin, ‘Audit Report for Laboratories of Biosafety Level 3 and Higher in Taiwan, 2007’. https://www.cdc.gov.tw/En/File/Get/53fR ... w22tKaDplw
[t.14 ] https://www.thelancet.com/journals/lani ... 73-3099(04)00911-9/fulltext
[t.15] Furmanski: https://armscontrolcenter.org/wp-conten ... 4-copy.pdf
[t.16] WHO post-outbreak biosafety guidelines for handling of SARS-CoV specimens and cultures. 18 Dec 2003. Accessible at: http://www.who.int/csr/sars/biosafety2003_12_18/en/
[t.17] Confirmation of leak in P4 lab, plus ‘waited 10 minutes’: https://www.publish.csiro.au/MA/pdf/MA08062
[t.18] For a mention of advanced French-made equipment: https://www.cbsnews.com/news/secret-wea ... wans-sars/
[t.19] Travel details: https://www.cidrap.umn.edu/news-perspec ... r-infected]
[t.20] Vaccine: https://english.president.gov.tw/NEWS/218

Beijing:

The main articles of investigative journalism are:
[b.1] Caijing magazine: ‘SARS virus leak investigation of health system vulnerability’ (21 May 2004) 财经杂志：《SARS病毒泄漏调查》, http://finance.sina.com.cn/g/20040521/1530772213.shtml, also https://history.ifeng.com/c/7uAfOBruATr. Gave some details on the known infection cases at the time, some via insiders, but did not offer any explanation for the leak.
[b.2] Sichuan News Network: ‘Accountability report after the return of SARS ’ . (7 Jul 2004) 四川新闻网：《SARS重来后的问责报告焦中国疾控中心原主任》. First article to give the broad reasons for the leak based on the official report of the Ministry of Health from the 1st July (not fully made public). It does not provide details of the circumstances. http://news.sina.com.cn/o/2004-07-07/00173008395s.shtml
[b.3] Southern Weekly: ‘SARS virus leakage accident “CDC accountability incident” review’ (8 Jul 2004) 南方周末：《SARS病毒泄漏事故“疾控中心问责事件”再追踪》, https://news.sina.com.cn/c/2004-07-09/11163655901.shtml, also http://finance.sina.com.cn/careerlife/2 ... 7988.shtml. First report giving the circumstances, especially about the sample fridge and the bad inactivation of the SARS strain.
[b.4] Xinmin Weekly: ;Virus leak: who should stand in the dock?’ (12 Jul 2004) 新民周刊：《病毒泄漏：谁该站上被告席》adds an insider report that the lab had been inspected in February and that problems had been raised, http://news.sina.com.cn/c/2004-07-12/13513683004.shtml
[b.5] China Science News: ‘Review of SARS virus leakage accident in laboratory ‘(25 Jul 2014): 中国科学报：《实验室SARS病毒泄漏事故回顾》, http://news.sciencenet.cn/htmlnews/2014 ... 5481036177 or http://news.yanfabu.com/article-9161-1.html
[b.6] Qingdao News (27 May 204): ‘Interview with Li, the first SARS patient in Beijing this spring: no longer fear anything’ http://qingdaonews.com/content/2004-05/ ... 175295.htm
[b.7] Beijing News, ‘The SARS accountability report announced that the time when Song was exposed to the virus is still a mystery (1 Jul 2004)’. With chain of contamination picture for 9 cases (Ren and Cui omitted): http://news.sohu.com/2004/07/01/59/news220795927.shtml
[b.8] Beijing News, ‘The SARS transmission chain is basically determined this spring (Figure)’. With important dates picture for 9 cases (Ren and Cui omitted): http://news.sohu.com/2004/07/01/59/news220795929.shtml

Official sources:

[b.9] People’s Daily Online and Jiangnan Time (20 Dec 2003), ‘The Nation’s emergency inventory of SARS laboratories’ : http://news.sina.com.cn/o/2003-12-20/10381388019s.shtml
[b.10] Beijing Evening News (19 Dec 2003), ’The nation cleans up SARS laboratories’: http://tech.sina.com.cn/other/2003-12-1 ... 0834.shtml
[b.11]. For a good short biography of Prof. Hong Tao see ‘Academician Hong Tao: worked hard all his life exploring the world of viruses’ (May 2020) https://dy.163.com/article/FCSAQ4K005371QFV.html
[b.12] Beijing Evening News (19 Dec 2003): ‘The nation will be held legally responsible for the infection caused by SARS laboratories in China’. http://news.sina.com.cn/c/2003-12-19/16281383514s.shtml
The air-lock is called a ‘reflection area’ in the Chinese text, which seems to be due to the kind of reflecting light which is used there. This refers to a ‘three areas-two buffers’ concept first outlined in the 2004 ‘General Biosafety Requirements for Laboratories’: clean / potentially contaminated / contaminated areas and two air-locks in between.
[b.13] National Health and Family Planning Commission of the People’s Republic of China (13 Oct 2003), ‘Our nation SARS laboratories are safe’ http://www.nhc.gov.cn/wsb/pzcjd/200804/23067.shtml
[b.14] China Youth Daily, on Song never having entered the P3 or worked with SARS: http://news.163.com/40702/8/0Q9891R60001124T.html
[b.15] Caijing (财经, ‘financier’ in English) is a well respected magazine and is still considered as being the most independent in the whole of China — a rarity. It nevertheless ran into trouble in 2009 (see https://www.csmonitor.com/World/Global- ... na-resigns).
Southern Weekly (南方周末), a weekly from the staunchly innovative and argumentative southern region of China, was eventually driven to the margins by the central government (see https://foreignpolicy.com/2015/01/29/so ... ensorship/).

Official conclusions:

[b51] Only extracts of the official ‘Analysis Report on the Epidemic Control of the ‘4.22’ SARS Epidemic in Beijing in 2004' (2004年北京‘4•22’SARS疫情流行控制情况分析报告) are known. The report misses the Ren and Cui cases from February. Note that the report title focuses on the April cases (‘4.22’), a possible odd justification for not mentioning the two primary February cases which explain the contamination of the lab.
[b52] The following extract includes some key tables and graph: http://www.39.net/HotSpecial/fdfy/xzbb/113011.html
[b53] Xinhuanet: Originated from Infection in the Laboratory-A Review of the SARS Epidemics in Beijing and Anhui this Spring(2004/07/01 19:12) http://news.sohu.com/2004/07/01/27/news220812709.shtml
[b54] Xinhuanet: The director of the Center for Disease Control and Prevention responsible for the the Beijing-Anhui SARS Accidents resigned (2004/07/01 19:13), http://news.sohu.com/2004/07/01/27/news220812700.shtml
[b55] Xinhuanet: Ministry of Health announces results of investigations into the causes of SARS epidemics in Beijing and Anhui (2004/07/01 21:03), http://news.sohu.com/2004/07/01/33/news220813351.shtml
[b56] Xinhuanet: Li Liming, director of the China Center for Disease Control and Prevention, and others resigned due to SARS in Beijing Huizhou , http://news.sohu.com/2004/07/01/24/news220802479.shtml (2004/07/01 10:21)
[b57] China Daily, ‘Officials punished for SARS virus leak’, 2 Jul 2004, http://www.chinadaily.com.cn/english/do ... 344755.htm
[b58] “People’s Daily”: Ministry of Health: The SARS outbreak in Beijing and Anhui this year came from laboratory infections”. 2 Jul 2004. Note how Ren and Cui cases are reported with no mention of a February infection. The original article seems to have been scrubbed out from People Daily website, but screenshots are easy to find in Chinese blogs. http://www.kunlunce.com/ssjj/guojipingl ... 40614.html, aslo archived at https://bit.ly/35wu8Mv

Chinese Blog entries:

[b100] A good Chinese entry on SARS leaks: ‘Thinking: The SARS virus leak in 2004’ Automated Translation: https://bit.ly/36mIgal. Original ‘思考: 2004年SARS病毒泄露事故’, should come up as first link in this Sogou search: https://bit.ly/2IsWRsh
[b101] Another good blog entry: ‘Investigation of SARS virus leakage in 2004’, http://www.juzizhoutou.net/tianren/lish ... /4868.html
[b102] For Cai Weiping’s quote see see blog entry: ’17 years after SARS, The CDC is now top in the world for its ability to identify viruses’ https://bit.ly/2IsPqlr, with approximate translation: https://bit.ly/38AvY0Q
[b103] Good summary of the delays caused by the Chlamydia controversy: ‘Interview丨Hu Shuli: How was the SARS coronavirus discovered?’, https://bit.ly/3poGlKS, approximate translation: https://bit.ly/2ItZPgH
[b104] Review of “SARS Virus Leakage in China P3 Laboratory”, blog entry: https://archive.is/19WLI
[b105] 2+3 labs: ‘Did the laboratory of the Chinese Center for Disease Control and Prevention leak the SARS virus in 2004?’, https://zhuanlan.zhihu.com/p/107322222
[b106] Another good blog entry: ‘A SARS virus leak that was about to be forgotten 16 years ago’. Original: https://bit.ly/35DWcxH, https://bit.ly/38No982 for approximate translation.

Additional Sources:

[b501] There are 4 Koch postulates in the original formulation, and 6 as modified by Rivers for viral diseases. See ‘Koch’s postulates fulfilled for SARS virus’ (May 2003) https://www.nature.com/articles/423240a
[b502] More details than published by the WHO were actually available of the site of the Chinese Consulate in Chicago on the same day: http://www.chinaconsulatechicago.org/ch ... t91985.htm
[b503] WHO press release on the 18th April: https://www.who.int/csr/don/2004_05_18a/en/
[b504] WHO press release of the 23rd April 2004, following the Chinese Ministry on Health announcement on the same day: https://www.who.int/csr/don/2004_04_23/en/
[b505] WHO Biosafety and Biosecurity in Health Laboratories — Report of a Regional Workshop, Pune, India, 8–11 July 2008. ‘SARS was acquired in the laboratory in Singapore and Taiwan in 2003 and in China in 2004. These occurred in a BSL3 laboratory in Singapore, a BSL4 in Taiwan and a BSL2 in China’. https://apps.who.int/iris/rest/bitstrea ... 1/retrieve
[b506] Paper by Zhong Nanshan, ‘What we have learnt from SARS epidemics in China: ‘https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550436/
[b507] ‘Bring critically ill patients to me’ Zhong Nanshan, https://news.cgtn.com/news/2020-09-08/Z ... index.html
[b508] Science Mag: ‘SARS Crisis Topples China Lab Chief’, Jul 2004: https://www.sciencemag.org/news/2004/07 ... -lab-chief
[b509] WHO press release of the 16th Apr 2003 confirming that SARS is caused by a coronavirus: https://www.who.int/csr/don/2003_04_16/en/
[b510] WHO press release on the 3rd Apr 2003 stating that ‘SARS, [..] is thought to be caused by a new virus in the coronavirus family’: https://www.who.int/csr/don/2003_04_03a/en/
[b511] All WHO SARS ‘Disease outbreak news’: https://www.who.int/csr/don/archive/dis ... ndrome/en/
[b512] WHO: ‘China confirms SARS infection in another previously reported case; summary of cases to date — Update 5’, 30 Apr 2004.www.who.int/csr/don/2004_04_30/en/
[b513] Bulletin of the World Health Organization, June 2004. Note the absence of mention of the two primary February cases (but an indirect reference to work on SARS in February and March). Also note: ‘Dr Merianos, who recently visited the Insti- tute for Virology in Beijing, could not say whether laboratories here or in other Chinese research facilities adhered to biosafety level 3.’ https://www.who.int/bulletin/volumes/82/6/en/news.pdf
[b514] Interestingly a paper by some Chinese scientists confirmed the count of 11 cases: Biomed Environ Sci, Dec 2006, a : ‘Severe acute respiratory syndrome — retrospect and lessons of 2004 outbreak in China’. Requests to get access to the full paper were not answered by the authors. https://pubmed.ncbi.nlm.nih.gov/17319269/.
[b515] WHO, 29 Apr 2004: ‘China confirms SARS infection in two previously reported cases — update 4’, https://www.who.int/csr/don/2004_04_29/en/
[b516] The-scientist.com, ‘SARS escaped Beijing lab twice’, Apr 2004 http://www.the-scientist.com/news-analy ... wice-50137
[b517] Article about a mobile P3 lab set in the old Institute building, ‘Between “yin and yang”, the reporter directly hit the laboratory test of the Institute for Disease Control and Virus Diseases’ , Jun 2020 https://www.sohu.com/a/404191251_206055
[b518] ‘Additional patients in China under investigation for SARS; WHO team travels to Beijing — update 2’, 26th Apr 2004, https://www.who.int/csr/don/2004_04_26/en/
[b519] ‘Surveillance and control of infectious atypical pneumonia in the interior of the country from January to May 2004’, 28 Jun 2004, http://www.nhc.gov.cn/bgt/pw10405/20040 ... 863b.shtml
[b520] WHO Situation Updates — SARS, https://www.who.int/csr/sars/archive/en/

On the chlamydia controversy

[b200] For an excellent recap of the events: ‘SARS virus hits China’s scientific research system’, Jun 2006, https://news.sina.com.cn/c/2003-06-11/01461156694.shtml, also through http://blog.sina.com.cn/s/blog_8d622a9e0100xgqb.html
[b201] A good recap of the Chlamydia hypothesis is available in ‘Hong Tao Chinas National CDC and the Chlamydia Hypothesis’, Flanders Health Blog, https://www.flandershealth.us/sars-outb ... hesis.html
[b203] For some important quotes from Hong Tao see The Bund Magazine (上海外滩画报) (2003 Apr 24) https://news.sina.com.cn/c/2003-04-24/08441013638.shtml
[b204] For the paper by Hong Tao linking SARS to Chlamydia: https://mall.cnki.net/magazine/Article/ ... 308004.htm, Aug 2008
[b205] Mistaken Identity of Germ Culprit Cost the Chinese Time and Prestige, WSJ, Jun 2004: https://www.wsj.com/articles/SB10546789 ... 6681095400
[b206] “Virologist Hong Tao, [ — ] said they had detected traces of coronavirus from three tissue samples. However, the team has not conducted follow-up research because it does not consider it a research focus.” http://www.china.org.cn/english/features/SARS/61091.htm
[b207] For the main paper by Hong Tao setting the case: ‘Chlamydia-like and coronavirus-like agents found in dead cases of atypical pneumonia by electron microscopy’ (1st Apr 2003): https://europepmc.org/article/med/12887816
“CONCLUSION: Since the novel Chlamydia-like agent was found co-existing with a coronavirus-like agent in the dead cases of SARS, it looks most likely that both the agents play some roles in the disease. At the present time, however, one can hardly determining how did these agents interact each other synergistically, or one follows another, need further study”

On nepotism:

[b301] Yi Ming, The problems of Chinese academia and their way out, Jul 2004 (亦明, 中国学术界的问题及其出路), http://bbs.tianya.cn/post-free-179032-1.shtml, with this excellent passage:

pquote]There was only one predecessor of these three laboratories, the laboratory of virus morphology and viral diarrhoea lab. In other words, yet another academician will not only create two more laboratories, but one of them is an “academician” laboratory showing that he does not even know what he is doing in it.

“It is no wonder that these people not only fail to share the worries and alleviate problems for the country, but also add chaos to the country. I have seen with my own eyes that a so-called senior academician controls a laboratory worth millions of dollars, but there is no one inside. Just because he is an academician, others dare not speak up against him. It was also this academician, shaking a few pieces of paper with the genetic sequence that had been stored in GenBank long ago, declaring that it was a scientific secret.

In fact, those “authorities” who have long lost their creative ability (in fact, many of them have never had any creative ability), the most fearful thing is to be looked down upon by others, afraid of being overtaken by others, so they cultivate a direct line in academia, a gang, and the goal of competition between gangs is not who has a new academic achievements, but who wins the prize.

The director of the laboratory that released the SARS virus again this year, the viral diarrhoea laboratory of the Institute for Viral Disease Control and Prevention, is the proud student of Academician Hong Tao. It’s really “Where there is a teacher, there is a disciple” (有其师必有其徒)! The academician system has also set an example for new academics in China: Those who work hard and do research are idiots, and those who can get on with nothing, or less, are “brilliant people with leadership skills.”[/quote]

[b302] For a good critic of the academic system in China, see ‘The disease of science lies in culture’, a discussion with Rao Yi, trained in the US (UCSF, Harvard) and known for his fight against corruption in academic system. https://www.sohu.com/a/48091593_183834
[b303] Wang Jiangwei’s CV: https://bit.ly/2IKlIZ6, archived here: https://bit.ly/3q4HHe9 (original), https://bit.ly/3fMhg8A (translation)
[b304] ‘Introduction to Laboratory Biosafety -Wang Jianwei’, https://wenku.baidu.com/view/1caa674169 ... beca8.html, archived at https://bit.ly/38KnWSW
[b305] For Dong Xiaoping role on WHO-China Coronavirus Disease Joint Expert Investigation Group: see https://www.who.int/docs/default-source ... 1a13fda0_2
[b306] Hong Tao’s medal for his contribution to a healthy China and epidemics prevention: https://bit.ly/3o16OwU (original), https://bit.ly/3q80Hsf (translation)