Showing posts with label SARS. Show all posts
Showing posts with label SARS. Show all posts

Friday, April 14, 2023

FOCUS: Vulnerability in China's Labs Allowed Pathogens to Escape, and It Could Happen Again

 

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The Biosafety Level 4 laboratory, center, on the campus of the Wuhan Institute of Virology in Wuhan, China, in May 2020. (photo: Hector Retamal/Bloomberg News)
FOCUS: Vulnerability in China's Labs Allowed Pathogens to Escape, and It Could Happen Again
Joby Warrick and David Willman, The Washington Post
Excerpt: "In the summer of 2019, a mysterious accident occurred inside a government-run biomedical complex in north-central China, a facility that handles a pathogen notorious for its ability to pass easily from animals to humans." 


China has poured billions of dollars into lab construction and genetic engineering in its bid to become a science superpower, but safety practices have failed to keep up, investigations and reports of accidents show

In the summer of 2019, a mysterious accident occurred inside a government-run biomedical complex in north-central China, a facility that handles a pathogen notorious for its ability to pass easily from animals to humans.

There were no alarms or flashing lights to alert workers to the defect in a sanitation system that was supposed to kill germs in the vaccine plant’s waste. When the system failed in late July that year, millions of airborne microbes began seeping invisibly from exhaust vents and drifting into nearby neighborhoods. Nearly a month passed before the problem was discovered and fixed, and four months before the public was informed. By then, at least 10,000 people had been exposed, with hundreds developing symptomatic illnesses, scientific studies later concluded.

The events occurred not in Wuhan, the city where the coronavirus pandemic began, but in another Chinese city, Lanzhou, 800 miles to the northwest. The leaking pathogens were bacteria that cause brucellosis, a common livestock disease that can lead to chronic illness or even death in humans if not treated. As the pandemic enters its fourth year, new details about the little-known Lanzhou incident offer a revealing glimpse into a much larger — and largely hidden — struggle with biosafety across China in late 2019, at the precise moment when both the brucellosis incident and the coronavirus outbreak were coming to light.

Multiple probes into both events by U.S. and international scientists and lawmakers are spotlighting what experts describe as China’s vulnerability to serious lab accidents, exposing problems that allowed deadly pathogens to escape in the past and could well do so again, potentially triggering another pandemic.

Beijing has embarked on a major expansion of the country’s biotechnology sector, pouring billions of dollars into constructing dozens of laboratories and encouraging cutting-edge — and sometimes controversial — research in fields including genetic engineering, and experimental vaccines and therapeutics. The expansion is part of a government-mandated effort to rival or surpass the scientific capabilities of the United States and other Western powers. Yet, safety practices in China’s new labs have failed to keep pace, a Washington Post examination has found.

Lab accidents happen everywhere, including in the United States, where illnesses and deaths caused by accidental infections have occurred, especially before the adoption of modern safety standards in the 1970s. But Chinese government reports, bolstered by interviews and statements by Western and Chinese officials and scientists who visited the facilities as recently as 2020, describe ongoing equipment problems and inadequate safety training that in some cases resulted in lab animals being illegally sold after being used in experiments, and contaminated lab waste being flushed into sewers. The problems are exacerbated, experts say, by a secretive, top-down bureaucracy that sets demanding goals while reflexively covering up accidents and discouraging any public acknowledgment of shortcomings.

China adopted legislation to improve biosafety around the time of the covid-19 outbreak caused by the novel coronavirus. But the lack of transparency makes it difficult to assess how the new standards are being implemented. The country’s recent history, which includes multiple documented instances of pathogen “leaks” or lab-related infections as well as a rushed entry into high-risk research with lethal viruses, provides ample reasons for concern, Western officials and experts say. Biosecurity expert Robert Hawley, who for years oversaw safety programs at the U.S. Army’s maximum-containment lab at Fort Detrick, Md., expressed dismay over “imprudent” lab practices he observed in inspection reports obtained by a congressional oversight committee.

“It is very, very apparent that their biological safety training is minimal,” Hawley said.

Multiple emailed requests seeking comment from the Chinese Embassy in Washington and China’s National Health Commission did not receive a response. Beijing has accused U.S. officials of scapegoating China over the coronavirus pandemic, while also rejecting criticism of China’s record on transparency and lab safety as hypocritical. U.S. agencies and institutions sometimes restrict access to scientific data, especially for defense-related research. In a 2020 State Department email obtained by the nonprofit organization U.S. Right to Know, a senior Trump administration official appeared to acknowledge that some criticism of China “called out actions that we ourselves are doing.”

Whether lab safety was a factor in the coronavirus outbreak remains unclear. The World Health Organization and the U.S. intelligence community both continue to point to a possible lab accident as one of the two ways that the pandemic may have started. In an updated intelligence assessment revealed publicly in February, Energy Department analysts joined the FBI in concluding that a lab leak was the most likely cause, although some other U.S. agencies continued to side with scientists who think a natural spillover from infected animals — perhaps raccoon dogs, sold at a Wuhan market — is to blame. Advocates of both theories expressed only low or moderate confidence in their conclusions.

Chinese officials have rejected the lab-leak hypothesis while also stymying independent investigations into the pandemic’s origins. For three years, Beijing has blocked access to information about the testing of humans and animals in the early weeks of the outbreak, and it also has refused to release a full inventory of the virus strains that were being studied at its top civilian and military virology labs.

What is clearer now is that conditions existed — and perhaps still exist — that raised the odds of an accidental outbreak. An expert group headed by Philip Zelikow, who was the executive director of the 9/11 Commission, is expected to highlight China’s struggles with biosafety as part of a wide-ranging report probing the conditions that set the stage for the global pandemic. Zelikow said the problem of lagging standards and unsafe working conditions for Chinese scientists was exacerbated by “an environment of extraordinary political and economic pressure.”

“Biosafety culture and practices struggled to keep up with racing biotech skills and ambitions,” he wrote in an email.

Shiny new labs

Twenty years ago, a different coronavirus ignited China’s ambition to become a biomedical superpower. The pathogen that causes the disease known as SARS, or severe acute respiratory syndrome, appeared out of nowhere in 2002, jumping from bats to a mongoose-like mammal known as the Asian palm civet and then to humans in China’s southeastern Guangdong province. Eventually, SARS infected more than 8,000 people worldwide, most of them in China and Hong Kong. About 800 died.

To China’s leaders, SARS exposed a vulnerability to zoonotic diseases — those that spread from animals to people. In the wake of SARS, Beijing vowed to rapidly modernize the country’s biomedical institutions, which were seen as lagging because of what official media termed a Western “stranglehold” on biotechnology.

Those promises were mostly kept, with technical and financial assistance from Western countries. The 15 years following the SARS eruption witnessed an unprecedented surge in Chinese partnerships with U.S. and European scientific institutions as Beijing sought to address the country’s serious health-care challenges while also narrowing the technology gap.

One of the most prominent collaborations was a U.S.-Chinese virology research project investigating coronaviruses, backed by millions of dollars in grants from the National Institutes of Health and involving China’s top scientist in the field, the Wuhan Institute of Virology’s Shi Zhengli, and counterparts from the New York-based nonprofit EcoHealth Alliance. Another collaboration was a Chinese-French agreement to construct China’s first ultra-secure laboratory — known as a Biosafety Level 4, or BSL-4 facility — built to handle the deadliest known pathogens. That lab, operated by the Wuhan Institute of Virology, became fully operational in 2018. Since then, Beijing has quickly built at least two more BSL-4 labs, in the cities of Harbin and Kunming, and announced plans to construct dozens of BSL-3s — labs that handle second-tier threats such as the anthrax bacteria — to ensure that each of China’s 34 provinces and autonomous regions has at least one — for a total of at least 120, according to a count by independent analysts.

Yet, for at least some labs, speed and ambition occasionally meant cutting corners.

Chinese officials said little publicly about a serious incident involving the SARS virus that occurred in 2004, when two lab workers in Beijing separately contracted the disease on the job and spread the illness to at least seven outsiders, one of whom died, WHO officials said. Meanwhile, as new labs were being built, the kinds of safety programs and rigorous training that developed over years in the top Western labs were slow to take hold, and in some cases were simply ignored, according to inspection documents and reports by Chinese scientists who visited or worked in the facilities.

The Washington Post reviewed official statements and reports, collected and translated by congressional researchers, State Department officials and independent investigators, that point to systemic failures in implementing safety standards necessary to prevent a spillover of dangerous bacteria and viruses. The deficiencies were being documented at a time of intense activity and rapid change. Across China, a sweeping, years-long effort was underway to collect and analyze thousands of previously unknown viruses harvested from wild animals across Asia. At the same time, Chinese labs were plunging headlong into the emerging field of synthetic biology, embracing new and controversial bioengineering techniques in which scientists tweak the genetic structure of viruses in an attempt to anticipate future evolutionary changes that could make the pathogens more dangerous to humans.

Yet, as Western countries discovered painfully years ago, running a successful laboratory requires more than just an ability to conduct experiments.

“It’s not just about the guys in white coats. It’s also about the people who run the systems,” said Hawley, the former Army biosafety chief. “You can’t cut corners. And you can’t glean the knowledge that’s required in a two-week course and then expect that people will be able to fly solo. It doesn’t happen that way.”

Flushed into sewers

In January 2020, as the first covid-19 cases were being investigated, Chinese news media reported a rare scandal involving one of the country’s laboratories. A 58-year-old professor at an agricultural university was arrested and charged with illegally selling animals used in the lab’s research program.

The Chinese authorities eventually sentenced the professor to 12 years in prison, a move apparently intended as a warning to others. The problem of off-the-books selling of lab animals was deemed to be of sufficient magnitude that China’s government was compelled to adopt a law that year expressly forbidding Chinese labs to sell “animals used in experimentation.”

Whether anyone became sick from exposure to laboratory animals is unknown. But the report amounted to an official acknowledgment of safety problems that are generally harder to spot and, in China’s case, only rarely mentioned in public.

Lab inspection reports and other documents obtained by congressional investigators and independent researchers show Chinese labs struggling to implement safety standards, including at some of the country’s newest and most prestigious institutions, such as the Wuhan BSL-4 lab. The essential conclusions also are echoed in confidential State Department cables drafted in 2018 after U.S. scientists visited the Wuhan facility and met with Chinese counterparts there. One cable noted a “serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.”

Although the Wuhan BSL-4 lab was built according to French designs, Chinese officials gradually shut out their French partners and replaced some of the costlier safety features with locally made equivalents that had never been put to the test under BSL-4 conditions, according to documents reviewed by The Post. For example, less than 18 months after the facility’s official opening, lab managers issued short-notice bids and patent applications to fix apparent problems with doors seals, the air filtration system and monitoring devices that were supposed to alert scientists to possible leaks. The records were obtained as part of an ongoing oversight investigation by the Senate Committee on Health, Education, Labor and Pensions and independent analysts with DRASTIC, a loose confederation of data analysts and amateur sleuths who mine open-source Chinese documents for information about covid-19. There is no known evidence suggesting that the BSL-4 facility was involved in research on the virus that causes covid-19; that research was taking place elsewhere at the Wuhan Institute.

Other documents describe a common litany of shortcomings at multiple facilities, including shortages of trained workers, inadequate or missing equipment, bad waste-management practices and generally sloppy conditions.

“There is a lot of debris in the laboratory,” an unnamed Chinese inspector noted in October 2019 after a visit to a secure research facility at Wuhan University, which operates a BSL-3 lab a short distance from the Wuhan Institute of Virology’s main campus. According to the inspection report, obtained by DRASTIC, lab conditions were “crowded and chaotic,” with “experiment and living area ... not separated” and “chemical waste and household waste mixed.”

At the Wuhan Institute of Virology, social media postings in late 2019 confirm previously reported safety lapses among lab workers conducting field research on unknown coronaviruses. Chinese scientists collected 20,000 virus samples from bats and other animals by 2019 and conducted genetic tests for hundreds of them, documents show. Social media postings show scientists working in caves filled with thousands of disease-carrying bats and sometimes handling the creatures and their excrement without gloves or other protective gear needed to prevent accidental infection.

Back in the laboratory, unidentified viruses were grown in petri dishes and tested under BSL-2 conditions, rather than in more-restrictive BSL-3 conditions, as would be customary in the United States and Western Europe, according to U.S. scientists who collaborated with the institute’s researchers. In a description of the research prepared for the Senate Health Committee, congressional researchers said that studies on previously unknown coronaviruses continued under “inappropriately low biosafety levels” until after the start of the coronavirus outbreak, and that the work included creating genetically modified “chimeras” by splicing genetic material from one virus onto another for lab tests. Wuhan Institute officials did not respond to a request for comment.

The problems were sufficiently worrisome that a few senior Chinese officials and scientists felt compelled to speak out. In a rare public acknowledgment, Gao Hucheng, a senior member of the government’s National People’s Congress, warned in a 2019 report to fellow legislators that the “biosecurity situation in our country is grim.” He specifically cited the potentially grave consequences stemming from “laboratories that leak.”

That same year, a second Chinese official acknowledged that his government had failed to adequately fund many of the high-containment labs it had built. Yuan Zhiming, a deputy director of the Wuhan Institute of Virology, said numerous high-level labs “have insufficient operational funds for routine, but vital, processes.”

“Currently, most laboratories lack specialized biosafety managers and engineers,” he wrote in 2019 in the Journal of Biosafety and Biosecurity. “This makes it difficult to identify and mitigate potential safety hazards in facility and equipment operation early enough.”

But the most widely cited deficiencies have involved flaws in handling hazardous laboratory wastes, a problem cited in inspection reports and other internal reviews of lab practices in different parts of China. In a 2018 report, obtained by Senate Health Committee investigators, an official in China’s southern Guangzhou region noted that “laboratory wastewater is being directly released” into sewage systems. The report described lab workers as careless in their handling of “highly dangerous” lab cultures, failing to properly clean up after experimenting with dangerous viruses and bacteria.

Similar problems were noted at Wuhan.

“Laboratories in China have paid insufficient attention to biological disposal,” said Yang Zhanqui, the director of the pathogen biology department at Wuhan University, in comments carried in 2020 by China’s Global Times, a publication closely aligned with the government. He cited a habit among researchers to “discharge laboratory materials into the sewer after experiments, without a specific biological disposal mechanism.”

Whether any live pathogens were released was unclear, inspection reports said, in part because of a failure by the labs to adequately monitor for leaks. Without adequate monitoring, leaks can continue unnoticed for long periods — which is precisely what happened in Lanzhou in the summer of 2019.

An invisible cloud of bacteria

As Chinese investigators later determined, the Lanzhou crisis began with a problem so simple that it could be grasped by anyone who has ever shopped for groceries: a lapsed expiration date.

It happened inside the Lanzhou Biopharmaceutical Plant, a manufacturer of vaccines that occupies a warehouselike building in the center of Lanzhou, a provincial capital with nearly 4 million inhabitants about 960 miles southwest of Beijing. The plant, which is ringed by high-rise apartment complexes on the southern bank of the Yellow River, was set up for the production of vaccines to prevent brucellosis.

Vaccine production started with live bacteria in fermentation tanks, and by the end of the process, the pathogens were normally killed with the use of chemical disinfectants. But somehow, in July 2019, the plant began using a chemical that was well past its prime, according to Chinese media accounts and interviews with scientists who investigated the accident. The waste-treatment regimen was only partly working, allowing many of the bacteria cells to survive.

A scholarly account of the accident released nearly three years later, in June 2022, describes a large plume of bacteria seeping from the exhaust stacks and then drifting toward the apartment buildings and a nearby veterinary school.

“The waste gas contained the notoriously easy-to-aerosolize pathogen, which was then further carried by southeast winds,” wrote Georgios Pappas, a Greek infectious-disease specialist and author of the report published in the journal Clinical Infectious Diseases. The result, Pappas said, was “possibly the largest laboratory accident in the history of infectious diseases.”

With no warning about the accident, people living downwind never had a chance to protect themselves.

Over the following weeks, students in the nearby veterinary school began developing unexplained symptoms: achy joints, fever, unusual fatigue. Even lab mice in the school’s research wing started becoming sick, and the females delivered stillborn babies. Local officials initially suspected an exposure from infected animals inside the school itself. But then residents in the nearby apartment complex began to fall ill.

One of them, a 39-year-old man who lived less than a block from the biopharmaceutical plant, told of how his health inexplicably deteriorated in the fall of 2019. “I suffered from severe back pain, sweating, sleepiness, and swelling,” the man, who gave the name Li Xiao, told the state-run Chinese news site the Paper months after the government officially acknowledged the mishap. “I didn’t know the reason at the time.”

The first official hint of a larger problem came on Dec. 27, 2019 — four months after the leak was halted — in the form of a paper notice tacked to bulletin boards in local neighborhoods, advising residents to sign up for free testing for brucellosis, a disease almost unknown in urban centers such as Lanzhou.

In the following months, the testing zone had to be expanded multiple times as sufferers were found miles downwind from the plant. State-run media accounts eventually acknowledged the outbreak and pinned the blame on the vaccine facility — eight managers were subsequently fired, and the plant shut down — while initially claiming that only a handful of residents had actually gotten sick.

In reality, out of nearly 70,000 people tested, more than 10,000 were seropositive, meaning enough brucellosis-causing bacteria had entered their lungs to trigger their immune systems into producing antibodies, Pappas said, citing figures compiled by the provincial health authorities in Lanzhou’s Gansu province.

How many symptomatic cases developed is unknown, but experts believe the number is in the hundreds. Some, like Lanzhou resident Li Xiao, were briefly hospitalized and then treated for months with different antibiotics. Nearly a year later, when interviewed by the Paper, he was still suffering from the effects of the disease, in addition to stomach pain from the drugs he was taking. After months of treatment, he said, he had decided to check out a local support group formed by neighbors whose experiences with brucellosis were similar to his.

“There are more than 400 people in this group,” he said. “As far as I know, almost every household in our community has infected patients.”

Chinese documents show that more than 3,000 people living near the plant applied for compensation, an indication of at least a mild illness, Pappas said. Three years after the events, the fact that more than 10,000 people were affected by the leak is “nowhere to be found in official data,” he told The Post. “It is as if these patients never existed.”

“This was a major event, with significant overtones, that nobody talked about,” Pappas said, “while the officials responsible for releasing relevant information failed, and still fail, to do so.”

Science hobbled by secrecy

Despite its scale, the Lanzhou accident barely made a blip in global media coverage. That’s partly because of official suppression, as initial Chinese accounts depicted only a minor mishap and very few illnesses. But those reports also coincide with panic over a different disease that erupted in Wuhan, one of China’s top biotechnology centers.

The first publicly recorded cases of covid-19 — then known only as a “pneumonia of unknown cause” in Chinese medical reports — occurred in December 2019, just before the brucellosis accident came to light. On Dec. 28, a day after Lanzhou residents were ordered to report for testing, medical investigators officially linked the Wuhan cases to a “novel coronavirus” that would be called SARS-CoV-2. Within a month, the virus had spread to cities throughout China, and then around the world.

Chinese officials initially refused even to acknowledge the problem at Wuhan and threatened punishment for any scientist or doctor who spoke out publicly. Epidemiologists believe the suppression campaign ultimately contributed to the rapid spread of the virus in the early weeks of the outbreak. It probably also hindered efforts to document precisely how and where the coronavirus emerged.

Chinese medical personnel who tried to sound the alarm in the early weeks of the pandemic were questioned by security officials and forced to confess publicly to “spreading rumors.” When World Health Organization representatives launched a formal investigation of the outbreak in 2020, Chinese officials barred the release of key information, including raw results from human and animal tests during the weeks when the first cases were emerging, or the genetic sequences for the strains of coronaviruses that scientists there had collected and studied. Later, some of the WHO contingent acknowledged being pressured by their Chinese hosts to issue public statements dismissing the possibility of a lab leak, even though they lacked the data to determine how the outbreak originated.

“The Chinese government doesn’t want to admit mistakes because it might challenge their image of being all-knowing and all-powerful,” said Alina Chan, a molecular biologist at the MIT-Harvard University Broad Institute and a co-author of “Viral,” a 2021 book that explores the events leading up to the pandemic. “And people on the ground are afraid of admitting mistakes because it could have very dire consequences for them.”

Pappas, the Greek physician who investigated the bacteria leak at Lanzhou, said China’s tendency toward concealment serves the country poorly. Not only does it impede efforts to fix real problems, he said, but it also fuels suspicions among outsiders of a coverup — even in cases where the suspicions are unwarranted.

“The paucity of information remains an issue for totalitarian regimes,” Pappas said. “The delay in notification of the initial SARS outbreak, the critical lost days on informing about specific characteristics of SARS-CoV-2, the absence of info on the Lanzhou leak — all belong to a common narrative: the absence of data, aiming to create a false sense of absence of events.”



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Sunday, March 1, 2020

FOCUS: You're Likely to Get the Coronavirus









Reader Supported News
01 March 20

It's Live on the HomePage Now:
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FOCUS: You're Likely to Get the Coronavirus
A worker sets up beds at the Hongshan Stadium to convert it into a makeshift hospital following an outbreak of the new coronavirus, in Wuhan, Hubei province, China February 4, 2020. (photo: China Daily/Reuters)
James Hamblin, The Atlantic
Hamblin writes: "Lipsitch predicts that within the coming year, some 40 to 70 percent of people around the world will be infected with the virus that causes COVID-19."



Most cases are not life-threatening, which is also what makes the virus a historic challenge to contain.

n May 1997, a 3-year-old boy developed what at first seemed like the common cold. When his symptoms—sore throat, fever, and cough—persisted for six days, he was taken to the Queen Elizabeth Hospital in Hong Kong. There his cough worsened, and he began gasping for air. Despite intensive care, the boy died.
Puzzled by his rapid deterioration, doctors sent a sample of the boy’s sputum to China’s Department of Health. But the standard testing protocol couldn’t fully identify the virus that had caused the disease. The chief virologist decided to ship some of the sample to colleagues in other countries.
At the U.S. Centers for Disease Control and Prevention in Atlanta, the boy’s sputum sat for a month, waiting for its turn in a slow process of antibody-matching analysis. The results eventually confirmed that this was a variant of influenza, the virus that has killed more people than any in history. But this type had never before been seen in humans. It was H5N1, or “avian flu,” discovered two decades prior, but known only to infect birds.
By then, it was August. Scientists sent distress signals around the world. The Chinese government swiftly killed 1.5 million chickens (over the protests of chicken farmers). Further cases were closely monitored and isolated. By the end of the year there were 18 known cases in humans. Six people died.
This was seen as a successful global response, and the virus was not seen again for years. In part, containment was possible because the disease was so severe: Those who got it became manifestly, extremely ill. H5N1 has a fatality rate of about 60 percent—if you get it, you’re likely to die. Yet since 2003, the virus has killed only 455 people. The much “milder” flu viruses, by contrast, kill fewer than 0.1 percent of people they infect, on average, but are responsible for hundreds of thousands of deaths every year.
Severe illness caused by viruses such as H5N1 also means that infected people can be identified and isolated, or that they died quickly. They do not walk around feeling just a little under the weather, seeding the virus. The new coronavirus (known technically as SARS-CoV-2) that has been spreading around the world can cause a respiratory illness that can be severe. The disease (known as COVID-19) seems to have a fatality rate of less than 2 percent—exponentially lower than most outbreaks that make global news. The virus has raised alarm not despite that low fatality rate, but because of it.
Coronaviruses are similar to influenza viruses in that they both contain single strands of RNA. Four coronaviruses commonly infect humans, causing colds. These are believed to have evolved in humans to maximize their own spread—which means sickening, but not killing, people. By contrast, the two prior novel coronavirus outbreaks—SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome, named for where the first outbreak occurred)—were picked up from animals, as was H5N1. These diseases were highly fatal to humans. If there were mild or asymptomatic cases, they were extremely few. Had there been more of them, the disease would have spread widely. Ultimately, SARS and MERS each killed fewer than 1,000 people.
COVID-19 is already reported to have killed more than twice that number. With its potent mix of characteristics, this virus is unlike most that capture popular attention: It is deadly, but not too deadly. It makes people sick, but not in predictable, uniquely identifiable ways. Last week, 14 Americans tested positive on a cruise ship in Japan despite feeling fine—the new virus may be most dangerous because, it seems, it may sometimes cause no symptoms at all.
The world has responded with unprecedented speed and mobilization of resources. The new virus was identified extremely quickly. Its genome was sequenced by Chinese scientists and shared around the world within weeks. The global scientific community has shared genomic and clinical data at unprecedented rates. Work on a vaccine is well under way. The Chinese government enacted dramatic containment measures, and the World Health Organization declared an emergency of international concern. All of this happened in a fraction of the time it took to even identify H5N1 in 1997. And yet the outbreak continues to spread.
The Harvard epidemiology professor Marc Lipsitch is exacting in his diction, even for an epidemiologist. Twice in our conversation he started to say something, then paused and said, “Actually, let me start again.” So it’s striking when one of the points he wanted to get exactly right was this: “I think the likely outcome is that it will ultimately not be containable.”
Containment is the first step in responding to any outbreak. In the case of COVID-19, the possibility (however implausible) of preventing a pandemic seemed to play out in a matter of days. Starting in January, China began cordoning off progressively larger areas, radiating outward from the city of Wuhan and eventually encapsulating some 100 million people. People were barred from leaving home, and lectured by drones if they were caught outside. Nonetheless, the virus has now been found in 24 countries.
Despite the apparent ineffectiveness of such measures—relative to their inordinate social and economic cost, at least—the crackdown continues to escalate. Under political pressure to “stop” the virus, last Thursday the Chinese government announced that officials in Hubei province would be going door-to-door, testing people for fevers and looking for signs of illness, then sending all potential cases to quarantine camps. But even with the ideal containment, the virus’s spread may have been inevitable. Testing people who are already extremely sick is an imperfect strategy if people can spread the virus without even feeling bad enough to stay home from work.
Lipsitch predicts that within the coming year, some 40 to 70 percent of people around the world will be infected with the virus that causes COVID-19. But, he clarifies emphatically, this does not mean that all will have severe illnesses. “It’s likely that many will have mild disease, or may be asymptomatic,” he said. As with influenza, which is often life-threatening to people with chronic health conditions and of older age, most cases pass without medical care. (Overall, about 14 percent of people with influenza have no symptoms.)
Lipsitch is far from alone in his belief that this virus will continue to spread widely. The emerging consensus among epidemiologists is that the most likely outcome of this outbreak is a new seasonal disease—a fifth “endemic” coronavirus. With the other four, people are not known to develop long-lasting immunity. If this one follows suit, and if the disease continues to be as severe as it is now, “cold and flu season” could become “cold and flu and COVID-19 season.”
At this point, it is not even known how many people are infected. As of Sunday, there have been 35 confirmed cases in the U.S., according to the World Health Organization. But Lipsitch’s “very, very rough” estimate when we spoke a week ago (banking on “multiple assumptions piled on top of each other,” he said) was that 100 or 200 people in the U.S. were infected. That’s all it would take to seed the disease widely. The rate of spread would depend on how contagious the disease is in milder cases. On Friday, Chinese scientists reported in the medical journal JAMA an apparent case of asymptomatic spread of the virus, from a patient with a normal chest CT scan. The researchers concluded with stolid understatement that if this finding is not a bizarre abnormality, “the prevention of COVID-19 infection would prove challenging.”
Even if Lipsitch’s estimates were off by orders of magnitude, they wouldn’t likely change the overall prognosis. “Two hundred cases of a flu-like illness during flu season—when you’re not testing for it—is very hard to detect,” Lipsitch said. “But it would be really good to know sooner rather than later whether that’s correct, or whether we’ve miscalculated something. The only way to do that is by testing.”
Originally, doctors in the U.S. were advised not to test people unless they had been to China or had contact with someone who had been diagnosed with the disease. Within the past two weeks, the CDC said it would start screening people in five U.S. cities, in an effort to give some idea of how many cases are actually out there. But tests are still not widely available. As of Friday, the Association of Public Health Laboratories said that only California, Nebraska, and Illinois had the capacity to test people for the virus.
With so little data, prognosis is difficult. But the concern that this virus is beyond containment—that it will be with us indefinitely—is nowhere more apparent than in the global race to find a vaccine, one of the clearest strategies for saving lives in the years to come.
Over the past month, stock prices of a small pharmaceutical company named Inovio have more than doubled. In mid-January, it reportedly discovered a vaccine for the new coronavirus. This claim has been repeated in many news reports, even though it is technically inaccurate. Like other drugs, vaccines require a long testing process to see whether they indeed protect people from disease, and do so safely. What this company—and others—has done is copy a bit of the virus’s RNA that one day could prove to work as a vaccine. It’s a promising first step, but to call it a discovery is like announcing a new surgery after sharpening a scalpel.
Though genetic sequencing is now extremely fast, making vaccines is as much art as science. It involves finding a viral sequence that will reliably cause a protective immune-system memory but not trigger an acute inflammatory response that would itself cause symptoms. (While the influenza vaccine cannot cause the flu, the CDC warns that it can cause “flu-like symptoms.”) Hitting this sweet spot requires testing, first in lab models and animals, and eventually in people. One does not simply ship a billion viral gene fragments around the world to be injected into everyone at the moment of discovery.
Inovio is far from the only small biotech company venturing to create a sequence that strikes that balance. Others include Moderna, CureVac, and Novavax. Academic researchers are also on the case, at Imperial College London and other universities, as are federal scientists in several countries, including at the U.S. National Institutes of Health. Anthony Fauci, the head of the NIH’s National Institute of Allergy and Infectious Diseases, wrote in JAMA in January that the agency was working at historic speed to find a vaccine. During the SARS outbreak in 2003, researchers moved from obtaining the genomic sequence of the virus and into a phase 1 clinical trial of a vaccine in 20 months. Fauci wrote that his team has since compressed that timeline to just over three months for other viruses, and for the new coronavirus, “they hope to move even faster.”
New models have sprung up in recent years, too, that promise to speed up vaccine development. One is the Coalition for Epidemic Preparedness (CEPI), which was launched in Norway in 2017 to finance and coordinate the development of new vaccines. Its founders include the governments of Norway and India, the Wellcome Trust, and the Bill & Melinda Gates Foundation. The group’s money is now flowing to Inovio and other small biotech start-ups, encouraging them to get into the risky business of vaccine development. The group’s CEO, Richard Hatchett, shares Fauci’s basic timeline vision—a COVID-19 vaccine ready for early phases of safety testing in April. If all goes well, by late summer testing could begin to see if the vaccine actually prevents disease.
Overall, if all pieces fell into place, Hatchett guesses it would be 12 to 18 months before an initial product could be deemed safe and effective. That timeline represents “a vast acceleration compared with the history of vaccine development,” he told me. But it’s also unprecedentedly ambitious. “Even to propose such a timeline at this point must be regarded as hugely aspirational,” he added.
Even if that idyllic year-long projection were realized, the novel product would still require manufacturing and distribution. “An important consideration is whether the underlying approach can then be scaled to produce millions or even billions of doses in coming years,” Hatchett said. Especially in an ongoing emergency, if borders closed and supply chains broke, distribution and production could prove difficult purely as a matter of logistics.
Fauci’s initial optimism seemed to wane, too. Last week he said that the process of vaccine development was proving “very difficult and very frustrating.” For all the advances in basic science, the process cannot proceed to an actual vaccine without extensive clinical testing, which requires manufacturing many vaccines and meticulously monitoring outcomes in people. The process could ultimately cost hundreds of millions of dollars—money that the NIH, start-ups, and universities don’t have. Nor do they have the production facilities and technology to mass-manufacture and distribute a vaccine.
Production of vaccines has long been contingent on investment from one of the handful of giant global pharmaceutical companies. At the Aspen Institute last week, Fauci lamented that none had yet to “step up” and commit to making the vaccine. “Companies that have the skill to be able to do it are not going to just sit around and have a warm facility, ready to go for when you need it,” he said. Even if they did, taking on a new product like this could mean massive losses, especially if the demand faded or if people, for complex reasons, chose not to use the product.
Making vaccines is so difficult, cost intensive, and high risk that in the 1980s, when drug companies began to incur legal costs over alleged harms caused by vaccines, many opted to simply quit making them. To incentivize the pharmaceutical industry to keep producing these vital products, the U.S. government offered to indemnify anyone claiming to have been harmed by a vaccine. The arrangement continues to this day. Even still, drug companies have generally found it more profitable to invest in the daily-use drugs for chronic conditions. And coronaviruses could present a particular challenge in that at their core they, like influenza viruses, contain single strands of RNA. This viral class is likely to mutate, and vaccines may need to be in constant development, as with the flu.
“If we’re putting all our hopes in a vaccine as being the answer, we’re in trouble,” Jason Schwartz, an assistant professor at Yale School of Public Health who studies vaccine policy, told me. The best-case scenario, as Schwartz sees it, is the one in which this vaccine development happens far too late to make a difference for the current outbreak. The real problem is that preparedness for this outbreak should have been happening for the past decade, ever since SARS. “Had we not set the SARS-vaccine-research program aside, we would have had a lot more of this foundational work that we could apply to this new, closely related virus, ” he said. But, as with Ebola, government funding and pharmaceutical-industry development evaporated once the sense of emergency lifted. “Some very early research ended up sitting on a shelf because that outbreak ended before a vaccine needed to be aggressively developed.”
On Saturday, Politico reported that the White House is preparing to ask Congress for $1 billion in emergency funding for a coronavirus response. This request, if it materialized, would come in the same month in which President Donald Trump released a new budget proposal that would cut key elements of pandemic preparedness—funding for the CDC, the NIH, and foreign aid.  
These long-term government investments matter because creating vaccines, antiviral medications, and other vital tools requires decades of serious investment, even when demand is low. Market-based economies often struggle to develop a product for which there is no immediate demand and to distribute products to the places they’re needed. CEPI has been touted as a promising model to incentivize vaccine development before an emergency begins, but the group also has skeptics. Last year, Doctors Without Borders wrote a scathing open letter, saying the model didn’t ensure equitable distribution or affordability. CEPI subsequently updated its policies to forefront equitable access, and Manuel Martin, a medical innovation and access adviser with Doctors Without Borders, told me last week that he’s now cautiously optimistic. “CEPI is absolutely promising, and we really hope that it will be successful in producing a novel vaccine,” he said. But he and his colleagues are “waiting to see how CEPI’s commitments play out in practice.”
These considerations matter not simply as humanitarian benevolence, but also as effective policy. Getting vaccines and other resources to the places where they will be most helpful is essential to stop disease from spreading widely. During the 2009 H1N1 flu outbreak, for example, Mexico was hit hard. In Australia, which was not, the government prevented exports by its pharmaceutical industry until it filled the Australian government’s order for vaccines. The more the world enters lockdown and self-preservation mode, the more difficult it could be to soberly assess risk and effectively distribute tools, from vaccines and respirator masks to food and hand soap.
Italy, Iran, and South Korea are now among the countries reporting quickly growing numbers of detected COVID-19 infections. Many countries have responded with containment attempts, despite the dubious efficacy and inherent harms of China’s historically unprecedented crackdown. Certain containment measures will be appropriate, but widely banning travel, closing down cities, and hoarding resources are not realistic solutions for an outbreak that lasts years. All of these measures come with risks of their own. Ultimately some pandemic responses will require opening borders, not closing them. At some point the expectation that any area will escape effects of COVID-19 must be abandoned: The disease must be seen as everyone’s problem.  



















MAGA's Jimmy Patronis Wants To Legalize Machine Guns.

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