While the world fights the coronavirus pandemic, China is fighting a propaganda war. Beijing’s war aim is simple: shift away from China all blame for the outbreak, the botched initial response, and its early spread into the broader world. At stake is China’s global reputation, as well as the potential of a fundamental shift away from China for trade and manufacturing. Also at risk is the personal legacy of General Secretary Xi Jinping, who has staked his legitimacy on his technocratic competence. After dealing with the first great global crisis of the 21st century, the world must fundamentally rethink its dependence on China.

Beijing’s Propaganda War

After months of staying holed up in the Forbidden City, Mr. Xi finally ventured to Wuhan, the epicenter of the virus, to declare victory over the virus as all the makeshift hospitals have been closed. Yet no one knows if Beijing’s claims that new indigenous cases are slowing down are true or not, given long-standing doubt about the veracity of any official Chinese statistics, and the party’s failure to act in the early days of the coronavirus.

The communist government instead is claiming that it has largely controlled the epidemic, even as it suspiciously now blames “foreign arrivals” for new cases of virus. Leaked video from China shows huge lines at a hospital in Chongqing, for example, raising questions about just what is happening around the country.

What Beijing cares about is clear from its sustained war on global public opinion. Chinese propaganda mouthpieces have launched a broad array of attacks against the facts, attempting to create a new narrative about China’s historic victory over the Wuhan virus. Chinese state media is praising the government’s “effective, responsible governance, » but the truth is that Beijing is culpable for the spread of the pathogen around China and the world. Chinese officials knew about the new virus back in December, and did nothing to warn their citizens or impose measures to curb it early on.

Instead of acting with necessary speed and transparency, the party-state looked to its own reputation and legitimacy. It threatened whistleblowers like the late Dr. Li Wenliang, and clamped down on social media to prevent both information about the virus and criticism of the Communist Party and government from spreading.

Unsurprisingly, China also has enablers abroad helping to whitewash Beijing’s culpability. World Health Organization Director-General Tedros Adhanom Ghebreyesus refused for months to declare a pandemic, and instead thanked China for “making us safer,” a comment straight out of an Orwell novel. This is the same WHO that has refused to allow Taiwan membership, due undoubtedly to Beijing’s influence over the WHO’s purse strings.

Most egregiously, some Chinese government officials have gone so far as to claim that the Wuhan virus was not indigenous to China at all, while others, like Mr. Tedros, suggest that China’s response somehow bought the world “time” to deal with the crisis. That such lines are being repeated by global officials and talking heads shows how effectively China’s propaganda machine is shaping the global narrative. The world is quickly coming to praise the Communist Party’s governance model, instead of condemn it.

The reality is that China did not tell its own people about the risk for weeks and refused to let in major foreign epidemiological teams, including from the U.S. Centers for Disease Control. Thus, the world could not get accurate information and laboratory samples early on. By then, it was too late to stop the virus from spreading, and other world capitals were as lax in imposing meaningful travel bans and quarantines as was Beijing.

Because of China’s initial failures, governments around the world, including democratic ones, now are being forced to take extraordinary actions that mimic to one degree or another Beijing’s authoritarian tendencies, thus remaking the world more in China’s image. Not least of the changes will be in more intrusive digital surveillance of citizens, so as to be able to better track and stop the spread of future epidemics, a step that might not have been necessary if Beijing was more open about the virus back in December and if the WHO had fulfilled its responsibilities earlier.

The Stakes for China and Globalization 

Regardless of how much some governments and global voices praise China, Xi and the Communist Party care about dominating the propaganda war because the Wuhan virus has stood their nation on a razor’s edge. Xi’s own legitimacy is not merely at stake. His government is ferociously fighting to divert blame and attention, fearing that the world rightfully may utterly reassess modern China, from its technocratic prowess to its safety. Decades of a carefully curated global image may crumble if nations around the globe start paying attention to China’s lax public health care, incompetent and intrusive government, and generally less developed domestic conditions.

Xi’s fears are well founded, as a global reconsideration of China is long overdue. Legitimate criticisms and doubts about China’s governance and growth model were long suppressed by Chinese pressure and the willingness of many to buy into the Communist Party’s public line. Public shaming of foreign corporations, global influence operations, and “elite capture” — all are policies Beijing has deployed to maintain China’s public image.

That carefully tended image is now cracked. Those concerned with global health issues may wonder why it is that China is wracked regularly by viral epidemics in addition to coronavirus, such as SARS, African Swine Fever, and avian flu (another outbreak is happening right now). Others may begin to look more carefully at China’s environmental devastation and the hundreds of thousands of premature deaths each year from air and water pollution.

On the trade side, many foreign corporations already have been reconsidering their operations in China, due to rampant intellectual property theft and rising production costs; now, they may seriously question how safe it is to continue to do business in China. Not only is the health of their employees at risk, but they no longer can be assured that China will be a stable supplier. If coronavirus becomes a seasonal phenomenon, as some experts predict, then even with a vaccine, new strains of the pathogen will always raise the specter of another out-of-control epidemic overwhelming the party-state’s capabilities and infecting the rest of the world.

More broadly, the pandemic of 2020 has brought doubts about globalization into the mainstream. Decades of open borders, unceasing intercontinental travel, study abroad, just-in-time inventory systems, and the like have created unexpected vulnerabilities in populations and economies thanks to unfettered openness. To worry about such weaknesses is not to adopt a Luddite reactionary stance, but to try and salvage the bases of the post-World War II global economic architecture.

Those who assumed that global markets were the optimal economic model and would always work, now have to consider whether globalization is the best system for dealing with pandemics like coronavirus, let alone old-fashioned state power plays like China imposed on Japan back in 2010, when it blocked the export of rare-earth minerals over territorial disputes in the East China Sea. Perhaps the biggest long-term economic effect of coronavirus will be on long-standing assumptions about global supply chains.

Because of the way the global economy has developed since 1980, to question globalization today is in large part to question the world’s relationship to China. As Sens. Marco Rubio and Tom Cotton have pointed out, America and the world have a prudential responsibility to reconsider their dependence on China.

It is only since the outbreak of the pandemic that Americans have come to learn that China is the major supplier for U.S. medicines. The first drug shortages, due to dependence on China, have already occurred. Eighty percent of America’s “active pharmaceutical ingredients” comes from abroad, primarily from China (and India); 45% of the penicillin used in the country is Chinese-made; as is nearly 100% of the ibuprofen. Rosemary Gibson, author of “China Rx,” testified last year to the U.S.-China Economic and Security Review Commission about this critical dependence, but nothing has changed in this most vital of supply chains.

The medicine story is repeated throughout the U.S. economy and the world. The unparalleled economic growth of China over the past generation has hollowed out domestic industries around the globe and also prevented other nations, such as Vietnam, from moving up the value-added chain. Many industries are quite frankly stuck with Chinese companies as their only or primary suppliers. Thus, the costs of finding producers other than China, what is known as “decoupling,” are exorbitant, and few countries currently can replicate China’s infrastructure and workforce.

Rethinking the Chinese Model and Globalization  

The world never should have been put at risk by the coronavirus. Equally, it never should have let itself become so economically dependent on China. The uniqueness of the coronavirus epidemic is to bring the two seemingly separate issues together. That is why Beijing is desperate to evade blame, not merely for its initial incompetence, but because the costs of the system it has built since 1980 are now coming into long-delayed focus. Coronavirus is a diabolus ex machina that threatens the bases of China’s modern interaction with foreign nations, from tourism to trade, and from cultural exchange to scientific collaboration.

Xi can best avoid this fate by adopting the very transparency that he and the party have assiduously avoided. Yet openness is a mortal threat to the continued rule of the CCP. The virus thus exposes the CCP’s mortal paradox, one which shows the paralysis at the heart of modern China. For this reason alone, the world’s dependence on China should be responsibly reduced.

To begin with, Washington must mandate that some significant percentage of major drugs, everyday medicines, first-aid material such as masks and gowns, and higher-end medical equipment like ventilators, will be produced domestically, so that we are better prepared for the next pandemic. In addition, controlling our own supply of vital medicines and equipment will allow Washington to continue to be able to assist other countries during similar emergencies, something we are not able to do with coronavirus and which Beijing is stepping in to take advantage of.

Second, America’s broader economic dependence on China needs to be reduced. Materials such as rare earths, 80% of which come from China, should be produced at home when possible, while the U.S. military needs to limit its exposure to Chinese goods for everything from transistors to tire rubber.

Thirdly, Washington must ensure that China does not capture the global semiconductor chip-making industry, which is a priority for Beijing. To surrender the crown jewel of the digital economy would put America in a position of permanent dependence vis-à-vis China.

The coronavirus pandemic is a turning point for China and the world. Today, Washington and other global capitals are solely responsible for the success or failure of their own efforts to control the Wuhan virus. In the short term, however, they should not let Mr. Xi and China get away with rewriting the history of the epidemic. In the longer run, they must look to reform globalization by prudently reshaping their economies and societies in the shadow of future crises.

Michael Auslin is a fellow at the Hoover Institution, Stanford University, and the author of “Asia’s New Geopolitics.”

Voir encore:

Time to ban wet markets

China’s rampant consumption of exotic animals and lack of hygiene standards is far from above criticism

Melissa Chen

March 18, 2020

Voir enfin:

First Sars, now the Wuhan coronavirus. Here’s why China should ban its wildlife trade forever

  • Both coronaviruses are linked to live animal markets, where sick, injured and dying animals are sold as exotic foods but end up transmitting disease
  • For too long, wildlife traders have been allowed to hide behind empty claims of medicine or conservation. It’s time to ban the unsavoury trade permanently
Peter J. Li

The deadly coronavirus, 2019-nCoV, has paralysed Wuhan and plunged China into a state of emergency. Sweeping across Chinese provinces, municipalities and special administrative regions, the epidemic has killed at least 106 people in the country.

With the death toll and number of infections climbing, this is turning into a major global public health crisis, similar to that caused by the severe acute respiratory syndrome (Sars) in 2003. People infected with the 2019-nCoV have been found in countries across North America, Europe, Southeast and South Asia.

The Wuhan coronavirus has confirmed the worst fears of many who have long called for an end to China’s wildlife wet markets. While two groups of scientists were debating whether the hosts of the 2019-nCoV were snakes, birds or mammals, the Chinese Centre for Disease Control and Prevention has confirmed, after successfully isolating the novel coronavirus in environmental samples collected from the Huanan Seafood Wholesale Market, that it came from wildlife animals sold in the market in downtown Hankou of Wuhan.

The first group of Wuhan’s 2019-nCoV patients were mostly traders at the market; one early patient had never visited it. The wet market had a section selling some 120 wildlife animals across 75 species. The first group of Wuhan patients is similar to the first group of Sars patients, who were also traders of wildlife in Guangdong.

All wildlife trade activities have now been banned after a notice by the agriculture and rural affairs ministry, the state administration for market regulation, and the state forestry. While the ban, which took effect on January 26, is temporary, aiming to suspend trade only until the epidemic is over, this joint action suggests the national government has finally accepted the findings of Chinese scientists.
Professor Zhong Nanshan China’s top Sars authority had proposed a lasting ban back in 2010, when he warned of a similar pandemic if wildlife markets remained open.
Professor Guan Yi , a Hong Kong University virologist who studied the Sars pathogen in 2003, had also made the same proposal. The 2019-nCoV is the huge price we are paying for snubbing the country’s top scientists.
There has long been a wildlife-eating subculture in southern China. But it was only over the past three decades that exotic foods became a status symbol. In parts of the country, you could order bear paws, pangolin meat and migratory birds.
Recent videos showing young women eating boiled bats caused a big stir. In 2014, a Guangxi businessman was sentenced to 13 years’ imprisonment for killing and eating a tiger.
China has a Wildlife Protection Law but critics say this protects business interests over wildlife. The State Forestry and Grassland Administration, the country’s authority for wildlife management, has practically become a spokesperson for wildlife business interests, despite the lessons of Sars. It is no surprise that eating wildlife has continued.

Wildlife businesses have been promoting their parochial interests as part of the national interest.

Tiger and rhino farms claim to operate in the interests of conservation.
Bear farm owners link their industry with public health. Many other wildlife-related businesses are protected for their alleged role in poverty reduction.
The wildlife trade ban is too late. Pangolins have been all but wiped out from the country’s valleys and forests. Snakes are rarely seen in much of south China, leading to serious ecological crises. No more than 30 Siberian tigers are thought to exist inside China.
Why sharks, rhinos, pangolins, sturgeon and giant salamanders are at risk of extinction

Bears in the wild have dropped by 93.4 per cent since the 1980s when bear farming began. Chinese wildlife traders now venture overseas for wildlife and their body parts. What Chinese customs manages to intercept is just the tip of the iceberg.

China’s wildlife markets have become a hotbed for diseases. Animals that are sick, dying of illness or injured during their capture and transport are not food, but health hazards. The workers who handle, kill and process the animals are vulnerable to viruses through cuts on their skin. The secretions of infected snakes can be aerosolised and breathed in by workers and shoppers alike.

Wildlife trade hurts rather than benefits China. Exotic foods constitute a mere fraction of the country’s 4.2 trillion yuan (US$605 billion) catering industry. Bear bile and other wildlife ingredients of traditional Chinese medicine are not life-saving drugs.

The brutal operation of bear farming has lost favour in the court of public opinion.

Rhino horns are not cures for cancer. Farming rhinos hurts China’s reputation. No government economic report has recognised the contribution of wildlife business to poverty reduction.

The just-issued trade ban should not be a temporary measure. It should be made a lasting policy. China has to choose between the narrow interests of wildlife businesses and the national interest of public health. It cannot allow a minority of wildlife traders and exotic food lovers to hijack the public interest of the entire nation.

Peter J. Li, PhD is associate professor of East Asian politics at the University of Houston-Downtown and a China policy specialist at Humane Society International

Voir par ailleurs:

How early signs of the coronavirus were spotted, spread and throttled in China
Gao Yu, Peng Yanfeng, Yang Rui, Feng Yuding, Ma Danmeng, Flynn Murphy, Han Wei and Timmy Shen
Caixin Global
Feb 29, 2020

The new coronavirus that has claimed nearly 3,000 lives and spread to more than 50 countries was sequenced in Chinese labs – and found to be similar to the severe acute respiratory syndrome (Sars) – weeks before officials publicly identified it as the cause of a mysterious viral pneumonia cluster in Wuhan, a Caixin investigation has found.

Test results from multiple labs in December suggested that there was an outbreak of a highly infectious virus. However, the results failed to trigger a response that could have prepared the public, despite being fed into an infectious disease control system that was designed to alert China’s top health officials about outbreaks.

The revelations show how health officials missed early opportunities to control the virus in the initial stages of the outbreak, as questions mount about who knew what and when, and whether these actions helped the disease to spread

As early as Dec 27, a Guangzhou-based genomics company had sequenced most of the virus from fluid samples from the lung of a 65-year old deliveryman who worked at the seafood market where many of the first cases emerged. The results showed an alarming similarity to the deadly Sars coronavirus that killed nearly 800 people between 2002 and 2003.

Around that time, local doctors sent at least eight other patient samples from hospitals around Wuhan to multiple Chinese genomics companies, including industry heavyweight BGI, as they worked to determine what was behind a growing number of cases of unexplained respiratory disease. The results all pointed to a dangerous Sars-like virus.

That was days before China notified the World Health Organisation (WHO) on Dec 31 about the emergence of an unidentified infectious disease, two weeks before it shared the virus’ genome sequence with the world, and crucially, more than three weeks before Chinese authorities confirmed publicly that the virus was spreading between people.

Concerns about the new disease were initially kept within a small group of medical workers, researchers and officials.

On Dec 30, Dr Li Wenliang was one of several in Wuhan who sounded the first alarms and released initial evidence online. Dr Li, who was punished for releasing the information, would perish from the disease five weeks later, after contracting it from a patient.

On Jan 1, after several batches of genome sequence results had been returned to hospitals and submitted to health authorities, an employee of one genomics company received a phone call from an official at the Hubei Provincial Health Commission, ordering the company to stop testing samples from Wuhan related to the new disease and destroy all existing samples.

The employee spoke on condition of anonymity, saying the company was told to immediately cease releasing test results and information about the tests, and report any future results to authorities.

Then on Jan 3, China’s National Health Commission (NHC), the nation’s top health authority, ordered institutions not to publish any information related to the unknown disease, and ordered labs to transfer any samples they had to designated testing institutions, or to destroy them. The order, which Caixin has seen, did not specify any designated testing institutions.

It was Jan 9 when the Chinese authorities finally announced that a novel coronavirus was behind Wuhan’s viral pneumonia outbreak. Even then, the transmissibility of the virus was downplayed, leaving the public unaware of the imminent danger.

Finally, on Jan 20, Dr Zhong Nanshan, a leading authority on respiratory health who came to national attention in his role fighting Sars, confirmed in a TV interview that the disease was spreading from person-to-person.

Two days later, Wuhan, a city of 11 million, was placed in lockdown. It remains quarantined today.

Social media posts provide clues

The earliest results, for the 65-year-old deliveryman who worked at the Wuhan seafood market, were returned on Dec 27 by Vision Medicals, a genomics company based in Huangpu district in Guangzhou, South China’s Guangdong province.

The patient was admitted to the Central Hospital of Wuhan on Dec 18 with pneumonia and his condition quickly deteriorated. On Dec 24, the doctors took fluid samples from his lungs and sent them to Vision Medicals for testing, according to Dr Zhao Su, head of respiratory medicine at the hospital.

In an unusual move, the company did not send back results, but instead called the doctor on Dec 27.

« They just called us and said it was a new coronavirus, » Dr Zhao said.

Vision Medicals confirmed the tests took place in a post it published on social media late last week. The post said the company was involved in early studies on the new coronavirus and contributed to an article published on the English version of the Chinese Medical Journal about its discovery. That article makes specific mention of a sample collected on Dec 24 from a 65-year-old patient who had contact with the seafood market.

A different social media post, believed to have been made by a Vision Medicals employee, sheds more light on the company’s early work. The author of the post, made on Jan 28, said only that they worked at a private company based in Huangpu, Guangzhou, where Vision Medicals is located.

The post’s author said they noticed a close similarity with the Sars coronavirus in test results of a sample collected on Dec 24, but decided to study the results more closely before returning them, due their significance. The company did, however, share the data with the Chinese Academy of Medical Sciences, according to the article.

On Dec 27, the lab worked had sequenced most of the virus’ genome and had confirmed it was a coronavirus similar to the Sars virus, the article said.

In the following days, company executives paid a visit to Wuhan to discuss their findings with local hospital officials and disease control authorities, the article said.

« There was an intensive and confidential investigation under way, and officials from the hospital and disease control centre had acknowledged many similar patients, » it said.

Little information about this early study has been officially released. The patient, who was transferred to Wuhan Jinyintang Hospital, later died.

Revelations triggered by ‘small mistake’

While researchers at Vision Medicals mulled their findings, the Central Hospital of Wuhan sent swabs from two other patients with the mysterious pneumonia to a Beijing-based lab, CapitalBio Medlab, for study.

One of the samples came from a 41-year-old man who had no history of contact with the seafood market, who was admitted on Dec 27.

Test results delivered by the company showed a false positive for Sars. It was a « small mistake », a gene-sequencing expert told Caixin, which may have been down to a limited gene database or a lack of retesting.

But it was this mistake that triggered the first concerns heard by the public – recalling painful memories of the cover-up that defined the Sars outbreak 17 years before

On the evening of Dec 30, several doctors in Wuhan, including the late Dr Li Wenliang, privately shared CapitalBio’s results as a warning to friends and colleagues to take protective measures.

Those messages then circulated widely online and sparked a public uproar demanding more information. Several people, including Dr Li and two other doctors who sent the messages that night, were later punished by the authorities for « spreading rumours ».

Dr Zhang Jixian, who heads the respiratory department at Hubei Xinhua Hospital, noticed on Dec 26 that he had received a growing number of patients with symptoms of pneumonia from the neighboring seafood market. He reported the situation to the hospital the next day, with that report passed on to city and provincial health authorities.

Following the reports, disease control authorities in Wuhan and Hubei on Dec 30 issued an internal notice warning of the emergence of pneumonia patients with links to the seafood market and requiring hospitals to monitor similar cases.

The notice, later leaked online, offered the first glimpse to the public of officials’ acknowledgement of the outbreak.

Silenced alarms

Several other genomics companies also tested samples from patients in Wuhan with the then-unidentified virus in late December, Caixin learnt.

Industry leader BGI received a sample from a Wuhan hospital on Dec 26. Sequencing was completed by Dec 29, and showed while it was not the virus that causes Sars, it was a previously unseen coronavirus that was about 80 per cent similar to it.

A BGI source told Caixin that when they undertook the sequencing project in late December the company was unaware that the virus had sickened many people. « We take a lot of sequencing commissions every day, » the source said.

Caixin has learnt that the Wuhan hospital sent BGI at least 30 samples from different pneumonia cases for sequencing in December, and three were found to contain the new coronavirus

In addition to the Dec 26 case, the second and third positive samples were received on Dec 29 and Dec 30. They were tested together and the results were reported to the Wuhan Municipal Health Commission as early as Jan 1.

On Jan 1, gene-sequencing companies received an order from Hubei’s health commission to stop testing and destroy all samples, according to an employee at one.

« If you test it in the future, be sure to report it to us, » the person said they were told by phone.

Two days later on Jan 3, the National Health Commission issued its gag order and said the Wuhan pneumonia samples needed to be treated as highly pathogenic microorganisms – and that any samples needed to be moved to approved testing facilities or destroyed.

One virologist told Caixin that even the Wuhan Institute of Virology (WIV) under the Chinese Academy of Sciences was not qualified for the tests and told to destroy samples in its lab.

But that day, Professor Zhang Yongzhen of Fudan University in Shanghai received biological samples packed in dry ice in metal boxes and shipped by rail from Wuhan Central Hospital. By Jan 5, Prof Zhang’s team had also identified the new, Sars-like coronavirus through using high-throughput sequencing.

Prof Zhang reported his findings to the Shanghai Municipal Health Commission as well as China’s National Health Commission, warning that the new virus was like Sars, and was being transmitted through the respiratory route. This sparked a secondary emergency response within the Chinese Centre for Disease Control and Prevention (CDC) on Jan 6.

On Jan 9, an expert team led by the CDC made a preliminary conclusion that the disease was caused by a new strain of coronavirus, according to Chinese state broadcaster CCTV.

On Jan 11, Prof Zhang’s team became the first to publish the genome sequence of the new virus on public databases Virological.org and GenBank, unveiling its structure to the world for the first time. The NHC shared the virus genomic information with the World Health Organisation the next day.

Also on Jan 11, the Wuhan Municipal Health Commission resumed updating infection cases of the new virus after suspending reports for several days. But the government repeated its claim that there had been no medical worker infections and that there was no evidence of human transmission.

Meanwhile, it reported that the number of confirmed cases had dropped to 41.

Voir enfin:

History and Recent Advances in Coronavirus Discovery

Kahn, Jeffrey S. MD, PhD*; McIntosh, Kenneth MD†

Author Information

The Pediatric Infectious Disease Journal: November 2005 – Volume 24 – Issue 11 – p S223-S227
doi: 10.1097/01.inf.0000188166.17324.60

Abstract

Human coronaviruses, first characterized in the 1960s, are responsible for a substantial proportion of upper respiratory tract infections in children. Since 2003, at least 5 new human coronaviruses have been identified, including the severe acute respiratory syndrome coronavirus, which caused significant morbidity and mortality. NL63, representing a group of newly identified group I coronaviruses that includes NL and the New Haven coronavirus, has been identified worldwide. These viruses are associated with both upper and lower respiratory tract disease and are likely common human pathogens. The global distribution of a newly identified group II coronavirus, HKU1, has not yet been established. Coronavirology has advanced significantly in the past few years. The SARS epidemic put the animal coronaviruses in the spotlight. The background and history relative to this important and expanding research area are reviewed here.

HISTORY

The history of human coronaviruses began in 1965 when Tyrrell and Bynoe1 found that they could passage a virus named B814. It was found in human embryonic tracheal organ cultures obtained from the respiratory tract of an adult with a common cold. The presence of an infectious agent was demonstrated by inoculating the medium from these cultures intranasally in human volunteers; colds were produced in a significant proportion of subjects, but Tyrrell and Bynoe were unable to grow the agent in tissue culture at that time. At about the same time, Hamre and Procknow2 were able to grow a virus with unusual properties in tissue culture from samples obtained from medical students with colds. Both B814 and Hamre’s virus, which she called 229E, were ether-sensitive and therefore presumably required a lipid-containing coat for infectivity, but these 2 viruses were not related to any known myxo- or paramyxoviruses. While working in the laboratory of Robert Chanock at the National Institutes of Health, McIntosh et al3 reported the recovery of multiple strains of ether-sensitive agents from the human respiratory tract by using a technique similar to that of Tyrrell and Bynoe. These viruses were termed “OC” to designate that they were grown in organ cultures.

Within the same time frame, Almeida and Tyrrell4 performed electron microscopy on fluids from organ cultures infected with B814 and found particles that resembled the infectious bronchitis virus of chickens. The particles were medium sized (80–150 nm), pleomorphic, membrane-coated, and covered with widely spaced club-shaped surface projections. The 229E agent identified by Hamre and Procknow2 and the previous OC viruses identified by McIntosh et al3 had a similar morphology (Fig. 1).

FIGURE 1.
FIGURE 1.:

Coronavirus OC16. Reprinted with permission from Proc Natl Acad Sci USA. 1967;57;933–940.

In the late 1960s, Tyrrell was leading a group of virologists working with the human strains and a number of animal viruses. These included infectious bronchitis virus, mouse hepatitis virus and transmissible gastroenteritis virus of swine, all of which had been demonstrated to be morphologically the same as seen through electron microscopy.5,6 This new group of viruses was named coronavirus (corona denoting the crown-like appearance of the surface projections) and was later officially accepted as a new genus of viruses.7

Ongoing research using serologic techniques has resulted in a considerable amount of information regarding the epidemiology of the human respiratory coronaviruses. It was found that in temperate climates, respiratory coronavirus infections occur more often in the winter and spring than in the summer and fall. Data revealed that coronavirus infections contribute as much as 35% of the total respiratory viral activity during epidemics. Overall, he proportion of adult colds produced by coronaviruses was estimated at 15%.8

In the 3 decades after discovery, human strains OC43 and 229E were studied exclusively, largely because they were the easiest ones to work with. OC43, adapted to growth in suckling mouse brain and subsequently to tissue culture, was found to be closely related to mouse hepatitis virus. Strain 229E was grown in tissue culture directly from clinical samples. The 2 viruses demonstrated periodicity, with large epidemics occurring at 2- to 3-year intervals.9 Strain 229E tended to be epidemic throughout the United States, whereas strain OC43 was more predisposed to localized outbreaks. As with many other respiratory viruses, reinfection was common.10 Infection could occur at any age, but it was most common in children.

Despite the extensive focus placed exclusively on strains 229E and OC43, it was clear that there were other coronavirus strains as well. As shown by Bradburne,11 coronavirus strain B814 was not serologically identical with either OC43 or 229E. Contributing to the various strain differences in the family of coronaviruses, McIntosh et al12 found that 3 of the 6 strains previously identified were only distantly related to OC43 or 229E.

Epidemiologic and volunteer inoculation studies found that respiratory coronaviruses were associated with a variety of respiratory illnesses; however, their pathogenicity was considered to be low.2,8,13,14 The predominant illness associated with infections was an upper respiratory infection with occasional cases of pneumonia in infants and young adults.15,16 These viruses were also shown to be able to produce asthma exacerbations in children as well as chronic bronchitis in adults and the elderly.17–19

While research was proceeding to explore the pathogenicity and epidemiology of the human coronaviruses, the number and importance of animal coronaviruses were growing rapidly. Coronaviruses were described that caused disease in multiple animal species, including rats, mice, chickens, turkeys, calves, dogs, cats, rabbits and pigs. Animal studies included, but were not limited to, research that focused on respiratory disorders. Study focus included disorders such as gastroenteritis, hepatitis and encephalitis in mice; pneumonitis and sialodacryoadenitis in rats; and infectious peritonitis in cats. Interest peaked particularly regarding areas of encephalitis produced by mouse hepatitis virus and peritonitis produced by infectious peritonitis virus in cats. Pathogenesis of these disease states was various and complex, demonstrating that the genus as a whole was capable of a wide variety of disease mechanisms.20 Human and animal coronaviruses were segregated into 3 broad groups based on their antigenic and genetic makeup. Group I contained virus 229E and other viruses, group II contained virus OC43 and group III was made up of avian infectious bronchitis virus and a number of related avian viruses.21

EMERGENCE OF THE SEVERE ACUTE RESPIRATORY SYNDROME (SARS) CORONAVIRUS

Given the enormous variety of animal coronaviruses, it was not surprising when the cause of a very new, severe acute respiratory syndrome, called SARS, emerged in 2002–2003 as a coronavirus from southern China and spread throughout the world with quantifiable speed.22–24 This virus grew fairly easily in tissue culture, enabling quick sequencing of the genome. Sequencing differed sufficiently from any of the known human or animal coronaviruses to place this virus into a new group, along with a virus that was subsequently cultured from Himalayan palm civets, from which it presumably had emerged.25

During the 2002–2003 outbreak, SARS infection was reported in 29 countries in North America, South America, Europe and Asia. Overall 8098 infected individuals were identified, with 774 SARS-related fatalities.26 It is still unclear how the virus entered the human population and whether the Himalayan palm civets were the natural reservoir for the virus. Sequence analysis of the virus isolated from the Himalayan palm civets revealed that this virus contained a 29-nucleotide sequence not found in most human isolates, in particular those involved in the worldwide spread of the epidemic.25 In the animal viruses, this nucleotide sequence maintains the integrity of the 10th open reading frame (ORF); whereas in the human strains, the absence of this motif results in 2 overlapping ORFs. The function of the ORFs in the animal and human isolates is unknown, and it is unclear whether the deletion of the 29-nucleotide sequence played a role in the transspecies jump, the capacity of the epidemic strain to spread between humans or the virulence of the virus in humans. Curiously data from seroepidemiologic studies conducted among food market workers in areas where the SARS epidemic likely began indicated that 40% of wild animal traders and 20% of individuals who slaughter animals were seropositive for SARS, although none had a history of SARS-like symptoms.25 These findings suggest that these individuals were exposed through their occupation to a SARS-like virus that frequently caused asymptomatic infection. Infection control policies may have contributed to the halt of the SARS epidemic. The last series of documented cases to date, in April 2004, were laboratory-acquired.

The SARS epidemic gave the world of coronaviruses an enormous infusion of energy and activity that contributed to the large amount already known about the virology and pathogenesis of coronavirus infections from the expanding area of veterinary virology.21

CORONAVIRUS GENOME AND STRUCTURE

Coronaviruses are medium-sized RNA viruses with a very characteristic appearance in electron micrographs of negatively stained preparations (Fig. 1). The nucleic acid is about 30 kb long, positive in sense, single stranded and polyadenylated. The RNA is the largest known viral RNA and codes for a large polyprotein. This polyprotein is cleaved by viral-encoded proteases to form the following: an RNA-dependent RNA polymerase and an ATPase helicase; a surface hemagglutinin-esterase protein present on OC43 and several other group II coronaviruses; the large surface glycoprotein (S protein) that forms the petal-shaped surface projections; a small envelope protein (E protein); a membrane glycoprotein (M protein); and a nucleocapsid protein (N protein) that forms a complex with the RNA. The coding functions of several other ORFs are not clear. The strategy of replication of coronaviruses involves a nested set of messenger RNAs with common polyadenylated 3-ends. Only the unique portion of the 5-end is translated.21 Mutations are common in nature. In addition, coronaviruses are capable of genetic recombination if 2 viruses infect the same cell at the same time.

All coronaviruses develop in the cytoplasm of infected cells (Fig. 2), budding into cytoplasmic vesicles from the endoplasmic reticulum. These vesicles are either extruded or released from the cell within the same time frame, and then the cell is destroyed.

FIGURE 2.
FIGURE 2.:

Strain 229E in WI-38 cells. Reprinted with permission from J Virol. 1967;1:1019–1027.

All group I coronaviruses, including 229E, use human aminopeptidase N as their cellular receptor.27 Mouse hepatitis virus, a group II coronavirus, uses a member of the carcinoembryonic antigen family as its receptor.28 The receptor for OC43 is not known, but it may be 1 of several cell surface molecules, including 9-O-acetylated neuraminic acid and the HLA-I molecule.29 The SARS coronavirus uses angiotensin-converting enzyme II as its cellular receptor.30,31

NEWLY IDENTIFIED GROUP I HUMAN CORONAVIRUSES

Since 2003, 5 new human coronaviruses have been discovered (Table 1). Three of these are group I viruses that are closely related and likely represent the same viral species. In 2004, van der Hoek et al32 reported the discovery of a new human coronavirus, NL63, isolated from a 7-month-old girl with coryza, conjunctivitis, fever and bronchiolitis. Using a novel genomic amplification technique, these investigators were able to sequence the entire viral genome. Phylogenetic analysis demonstrated that this virus was a group I coronavirus related to 229E and transmissible gastroenteritis virus, a virus of pigs. Screening of 614 respiratory specimens collected between December 2002 and April 2003 turned up 7 additional individuals who tested positive for NL63. All had upper or lower respiratory tract disease or both.

TABLE 1
TABLE 1:

Recent Discoveries of Human Coronaviruses

Shortly after, Fouchier et al33 reported the identification of a coronavirus, named NL, isolated from an 8-month-old boy with pneumonia and grown from a clinical specimen that was obtained in April 1988. Genomic amplification techniques, based on arbitrarily primed reverse transcriptase-polymerase chain reaction (RT-PCR), were used to identify viral sequences. Full genomic sequence analysis of NL showed that this virus was also a group I coronavirus and closely related to NL63. Four of 139 (2.9%) respiratory specimens collected from November 2000 to January 2002 tested positive for NL.33 Respiratory tract disease was observed in these 4 children whose ages ranged from 3 months to 10 years. The discovery of both NL63 and NL depended on the propagation of the viruses in cell culture.

With the use of molecular probes that targeted conserved regions of the coronavirus genome, months later, Esper et al found evidence of a human respiratory coronavirus in respiratory specimens obtained from children younger than 5 years of age, which was designated the New Haven coronavirus (HCoV-NH). This approach was based on the theory that the gene for the viral replicase of all coronaviruses has conserved genetic sequences that encode indispensable, essential functions and that these sequences could be targeted for virus identification and discovery. This approach did not require propagation of the virus in cell culture, organ cultures or experimental animals and could be performed directly on respiratory secretions. After the initial identification of novel sequences of HCoV-NH, specific probes were used to screen respiratory specimens collected between January 2002 and February 2003 from children younger than 5 years of age whose respiratory specimen tested negative for respiratory syncytial virus, influenza, parainfluenza and adenoviruses. Of 895 children, 79 (8.8%) tested positive for HCoV-NH by RT-PCR, a majority of whom were sampled in the winter and spring seasons.34 Sequence and phylogenetic analysis based on the replicase gene showed that HCoV-NH was closely related to both NL63 and NL, although the full genomic sequence of HCoV-NH has not been completed. Cough, rhinorrhea and tachypnea were present in more than one-half of the children infected with HCoV-NH. Eleven children were in the newborn intensive care unit at the time of their sampling and had been hospitalized since birth, suggesting either nosocomial infection or a less likely cause of vertical transmission.

One child, a 6-month-old who tested positive for HCoV-NH, also carried a diagnosis of Kawasaki disease, a vasculitis of early childhood. In a subsequent case-control study, 8 of 11 (72.7%) children with Kawasaki disease tested positive for HCoV-NH while only 1 of 22 (4.5%) age- and time-matched controls tested positive for HCoV-NH (P = 0.0015).36 By correlating these findings, Graf37 detected the presence of a peptide corresponding to the spike glycoprotein of NL63, the closely related virus identified in the Netherlands, in tissue from individuals with Kawasaki disease. The summation of these findings suggests that HCoV-NH may play a role in the pathogenesis of Kawasaki disease. Further research is necessary to determine whether HCoV-NH is the cause of Kawasaki disease.

NEWLY IDENTIFIED GROUP II HUMAN CORONAVIRUSES

In January 2001, a 71-year-old man who had recently returned from Shen-zhen, China, a previously SARS-endemic area, presented in Hong Kong with a fever and productive cough. Although his SARS screening was negative, a novel group II coronavirus sequence was amplified by RT-PCR from his respiratory specimen with the use of primers that targeted conserved regions of the viral replicase gene.35 This novel virus, designated HKU1, was genetically distinct from OC43, the other known human group II coronavirus. This virus could not be propagated in cell culture. Seroepidemiologic studies, based on antibodies reacting with a recombinant HKU1 nucleocapsid, suggested that human infection with HKU1 might be common.35 However, it is unclear whether the enzyme-linked immunosorbent and Western blot assays used to detect HKU1 antibody were also detecting cross-reactive antibody to OC43 or other human coronaviruses.

SUMMARY

The field of coronavirology has advanced significantly in recent years. The SARS epidemic was a dramatic reminder that animal coronaviruses are potential threats to the human population, although the exact mechanism of species-to-species spread of the SARS coronavirus remains obscure. NL63 has been identified in many countries. This virus and the related viruses NL and HCoV-NH are likely the cause of a substantial proportion of respiratory tract disease in infants and children. The impact of HKU1 is not yet known. It seems clear that the coronaviruses infecting humans and causing respiratory disease are heterogeneous and quite widely distributed among groups I and II. It may be that some of the newer coronaviruses represent strains similar to the original B814 and OC strains that could not be further characterized in the 1960s. Additional human coronavirus strains will very likely be discovered, which stresses the need for further investigation into the virology and etiology of these infectious organisms.

DISCUSSION

Question: What is the actual clinical impact of coronaviruses on infectious disease prevalence and severity in the child and adult population?

Kenneth McIntosh, MD: Coronaviruses are common, and they are generally related to the upper respiratory tract family of disorders. They also trigger asthma in children and adults and severe respiratory disease in the elderly. Under the bell-shaped curve of respiratory infection, they probably cause pneumonia and bronchiolitis infections in the infant and child population. The clinical impact of coronaviruses has not yet been fully determined because much still remains to be discovered, despite recent research advances.

Question: Overwhelmingly SARS seemed to have its greatest problems in the adult population, which probably has a lot to do with how it entered the human population and was spread. Did SARS present to be as much of a problem for babies and children?

Kenneth McIntosh, MD: No, interestingly enough SARS did not seem to be as much of a threat to infants and children. The infection appeared to be less severe in babies, and babies were also less infectious. This was evident by looking at the trend of secondary cases that developed. This is in marked contrast to the age-related severity of most respiratory viral infections. These data have provoked considerable interest and discussion, but no good explanation has surfaced. My own theory relates to the fact that almost all respiratory viral infections in adults are reinfections, and these occur on a background of partial immunity. Theoretically, if you took a virus like RSV or parainfluenza and introduced it for the first time into the human population, adults, who are infected and have no preexisting immunity, might develop more severe disease than babies. However, until further research can verify this, it can only be seen as a theory.

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