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The coronavirus epidemic
The virus, known for its distinctive crown or “corona” when studied under an electron microscope, almost certainly rested harmlessly in horseshoe bats in China’s Yunnan province for years before spreading to a mystery, intermediate animal host.
Some time in November last year, this new type of coronavirus won the pathogen lottery. A single copy of the genetic code embedded itself in a secondary host, perhaps a cat-like civet, and mutated – just once – in precisely the right way, giving it the keys to human beings.
It was, according to viral evolution experts, a “one-jump” event into a human host. A fluke.
But viruses are the great chancers of modern infection, and this was not without precedent. The same family of pathogens produced the severe acute respiratory syndrome (SARS) virus, which leapt to humans in China via the same gene receptor in late 2002 before spreading across the globe, making 8000 people sick and killing about 800.
Viruses mutate fast, giving them a sort of brute force to crack the combination lock of the human genome. It was only a matter of time before one of the dozens of bat coronaviruses stumbled blindly onto the right genetic sequence that would give it access to the human world. Eighteen years, as it turns out.
What health officials are now calling the 2019 novel coronavirus (2019-nCoV) stalked the public without detection for days after it made the species crossover in November. The first signs of human infection – although the case was not confirmed until weeks later – showed up on December 1, according to early research published in medical journal The Lancet.
That study tracked the clinical details and backgrounds of the first 41 laboratory-confirmed cases of 2019-nCoV, allowing scientists and public health authorities to piece together the crucial first moments of an epidemic about which we know precious little.
According to The Lancet, a further five people in Wuhan, the capital city of China’s central Hubei province, began to show symptoms between December 1 and 15. These cases would ultimately present to local health authorities as a type of viral pneumonia “of unknown cause”. The first of these would not make it to a hospital until December 16.
As the cluster grew, authorities stalled. For two weeks, the pathogen moved totally unrestricted through Wuhan, a city with a population of 11 million people.
There would be another 31 cases, all with mysterious pneumonia presentations of unknown origin. Many of these patients had been at a market in Wuhan before Chinese officials issued an epidemiological alert on December 31.
It was at this venue, the Huanan Seafood Market, where clusters of the pathogen first became evident. It should have been a clue that something new was happening. But it’s unlikely this hub of wild animal trade – where snakes, birds, fish and crustaceans, other reptiles and scores of different species of mammals are often killed live and gutted for customers – was the epicentre of this outbreak.
According to the data in the Lancet paper, it couldn’t have been.
The patient who first showed symptoms, on December 1, had no connection to the seafood market.
“The virus came into that marketplace before it came out of that marketplace,” Georgetown University adjunct professor of infectious diseases Daniel Lucey told the academic journal Science on January 26.
When the outbreak alarm was sounded on New Year’s Eve, authorities closed in on Wuhan, knowing the eyes of the world were on them. The World Health Organization (WHO) was notified the same day.
The Chinese Center for Disease Control and Prevention “dispatched a rapid response team to accompany Hubei provincial and Wuhan city health authorities” to begin an investigation into the nature of the pathogen and its origin. This team included scientists from the National Institute for Viral Disease Control and Prevention, who managed to sequence the virus genome in three patients by the end of that week.
It was an astonishing achievement. SARS wasn’t laid bare genetically until five months after the first cases were reported.
Scripps Research director of infectious disease genomics Kristian Andersen told health policy publication Stat News that the speed at which scientists unravelled the novel coronavirus genome is “unprecedented and completely unbelievable”.
“It’s just insane,” he said.
Viruses may strike many as being primitive, but they are by no means simple. And coronaviruses in particular, which have the largest genomes known among RNA viruses, contain up to 30,000 nucleotides, the basic building blocks of DNA and RNA, according to research published in the scientific journal Proceedings of the National Academy of Sciences.
China’s genome breakthrough with 2019-nCoV, which included the worldwide sharing of the sequences from January 10, was a crucial moment in the early fight to contain the virus.
First, it allowed authorities to deploy the best real-time diagnostic test in laboratories. These tests code the virus RNA genome into a complementary DNA profile, which can then be amplified to identify target sequences. No genome, no fast diagnosis.
Second, comparing the genomes of the virus at the beginning of the outbreak can reveal how long it has been in the “wild” and, as the epidemic spreads, whether it is mutating. RNA is less stable than DNA as a base for life, which is why viruses prefer it – it allows them to change quickly.
“The virus, which is an RNA virus prone to replication errors, may well mutate and evolve in the coming months and years,” says former United States Centers for Disease Control and Prevention director Tom Frieden.
“… This coronavirus behaves somewhat like SARS, which it resembles genetically, but is much less deadly, and possibly more infectious.”
The virus genome from the first three patients was practically identical, which means it likely shared a common, very recent ancestor because it had not yet mutated.
From the first alert, scientists struggled to get a handle on the rate at which the novel coronavirus reproduces and spreads. The SARS virus had an early reproductive number, an R0 value, of about 3, which meant that initially one patient infected three people, who each went on to infect three people. The R0 fell to less than 0.4 after control measures began to bite.
Estimates suggest the R0 for the novel coronavirus is between 2 and 3.
On January 9, two days after China had confirmed it had a new human strain of coronavirus, WHO released a statement saying it had no specific recommendations for travellers.
“WHO advises against the application of any travel or trade restrictions on China based on the information currently available,” the statement read. “China has strong public health capacities and resources to respond and manage respiratory disease outbreaks.”
Indeed, authorities had acted swiftly at first by shutting down the Huanan Seafood Market in Wuhan. But subsequent information revealed that local officials in China must have known, even then, that this disease could not have come from the wet market.
On January 10, WHO released a “disease commodity package” with resources for global health authorities that listed the status of the outbreak.
“Epidemic Potential: Under investigation,” it said.
It also noted, however, that despite the genome of the virus being available for the quick diagnostic tests, none were commercially available and this was slowing identification of the disease spread.
The following day, the Wuhan Municipal Health Commission released an update on its investigation, noting: “Patients were mainly operating and purchasing [from the] Huanan Seafood Market in Wuhan City.
“… No new cases have been detected since January 3, 2020. At present, no medical staff infections have been found, and no clear evidence of human-to-human transmission has been found,” the statement says.
“Our city will continue to strengthen patient treatment, epidemiological investigations, carry out in-depth patriotic health campaigns, do a good job in spreading knowledge of disease prevention, and safeguard the health of the people.”
Questions have since emerged about this statement from Wuhan. Local officials must have known there were more infections than the 41 people on their books. Had their investigation been more thorough, or more transparent, they also would’ve known that shutting the market would not stop the spread of infection.
What followed was a rapid escalation in the threat.
On January 12, one confirmed case showed up in Thailand. Then, on January 15 and 19, two more cases popped up in Japan. All these patients had travelled from China.
By January 20, Chinese authorities had confirmed the first case of human-to-human transmission in Guangdong province. This was a significant development because, until then, public health professionals were not sure if this was possible. They had thought – hoped, really – that all affected had been infected by contaminated animals.
In reality, however, the virus was jumping from human to human from at least January 4, according to another study later published in The Lancet. It was drifting through the population, sometimes spread by people who were asymptomatic. “These cryptic cases of walking pneumonia might serve as a possible source to propagate the outbreak,” the paper said.
Having studied five patients in the same family who all tested positive for 2019-nCoV, the researchers wrote, “The possibility of person-to-person transmission could not be excluded, as seen in this family cluster with no known history of exposure to markets or animals, and rapid intercity spread might be possible by air travel. Vigilant epidemiological control in the community and health-care facilities is important to prevent another SARS-like epidemic.”
Despite these warnings and the emerging evidence, WHO was yet to declare an emergency. It had also not changed its travel advice since January 9. At this stage, there were 217 confirmed cases of novel coronavirus in China and two other countries with four dead.
On the same day as the news about human-to-human transmission, January 20, it was reported that the virus had made it to South Korea, also through a person travelling from China.
WHO hastily called the first meeting of its Emergency Committee, with a follow-up a day later. Expert advisers were split on whether the unfolding drama in China constituted a public health emergency of international concern (PHEIC).
“I am not declaring the new coronavirus outbreak a public health emergency of international concern today,” WHO director-general Tedros Adhanom Ghebreyesus said after the second meeting on January 23.
“The Emergency Committee was divided over whether the outbreak represents a PHEIC. This is an emergency in China, but it has not yet become a global health emergency.”
The same day, the number of confirmed cases in China jumped to 557. Then things began to move exponentially.
The number of infections was revised up to 835 lab-confirmed cases with 25 dead. The health facilities in Wuhan were overwhelmed. Chinese state media announced that two hospitals, one with 1000 beds and the other with 1300, would be built from scratch in just 10 days. Video of a vast, barren worksite filled with heavy machinery working in tandem accompanied the news.
Both hospitals are due to open next week.
China’s central government blockaded 13 cities in Hubei province on January 24, putting 41 million people into lockdown. Just 24 hours later, this quarantine was expanded to 18 cities and 57 million people – a population more than double that of Australia.
Public health workers in Australia had been only distantly following the news of a new virus circulating throughout central China; they were more worried about a measles cluster arriving from the Pacific Islands.
That changed quickly, following the first meeting of the WHO Emergency Committee. As the total worldwide number of cases soared to 1321 with 41 dead, the first Australian coronavirus infection was diagnosed in Melbourne. Hours later, the New South Wales chief health officer, Dr Kerry Chant, confirmed three more cases.
“The briefings were changing pretty quickly,” one source familiar with the NSW government public health response told The Saturday Paper. “They knew that we were in a situation where the advice would not be the same in a few hours as it was when it was given.”
The internal confusion spilled over into the public as authorities gave competing advice about whether children should stay home from school. Eventually it was settled – parents were told that any child who had returned from China should remain at home for two weeks to wait out the incubation period of any possible infection.
Testing suspected cases was also something of a seat-of-the-pants operation. At first, only those who had travelled from Wuhan and were displaying symptoms were required to present themselves to health officials. Then it was Hubei province and, late on Tuesday night, anyone who had returned from anywhere in China with symptoms.
On Wednesday, Chant revealed that this expanded regimen of testing had boosted the number of people under observation from about six in the days prior to 16. The cases ticked up. Five, six.
Electronic databases in NSW hospitals began to flag keywords such as “cough” or “chest infection” and “China” if patients complained of an illness, alerting authorities to follow up.
Meanwhile, a team of molecular biologists and other specialists at the University of Queensland had already started the ultimate race: trying to develop a vaccine for the pathogen.
The alert came via the Coalition for Epidemic Preparedness Innovations (CEPI), which knew the UQ team had developed and patented a special “molecular clamp”. This technology allows for the development of synthetic “subunit” vaccines, which work without disabling the ability of the patient’s own immune system to adapt to the threat. In other words, the UQ team could build a fake virus that teaches our body to fight the real one.
CEPI had previously given the team a grant as a sort of insurance policy against future epidemics. On January 24, CEPI made its first claim.
“Ambitious is certainly the word for it,” Professor Paul Young, head of UQ’s School of Chemistry and Molecular Biosciences, tells The Saturday Paper.
“The grant call that we answered from CEPI stipulated that they were interested in platforms that could develop a product or at least a candidate vaccine from discovery of a pathogen within 16 weeks.
“So, I mean, that is an extraordinary challenge in and of itself.”
It will likely take six to nine months “at best”, Young says, to get a vaccine through human trials and into large-scale manufacturing.
But none of this would have been possible without the genome sequences that were decoded and published for the world by Chinese scientists at mind-boggling speed.
“We are not the only ones with platforms that are attempting to drive production of a vaccine in a rapid turnaround time,” says Young, “and virtually all of them are dependent on that initial genetic sequence.”
Given the ubiquity of the coronavirus family of pathogens, Young and his team knew exactly what sequence they needed to isolate from the 2019-nCoV genome – the spike protein. This is the molecule that gives the virus its distinctive crown – the spike – and also helps it bind with and enter human cells. Acting like a signpost, this protein is targeted by our bodies in a natural response to infection.
“You are basically mimicking the immune stimulus that the virus would naturally provide to the immune system, but not in a virus form, in a synthetic form,” Young says.
The UQ team is about 20-strong, with more drafted in from across the university and further afield. They work in shifts, late into the evening during the week and over the weekend.
“We are trying to do it in a shift form,” Young says, “but there are certain expertises held by certain members of our staff … It is a constant run at the moment.”
As the team leaned into the work, the number of coronavirus victims rose sharply. On January 26, 1975 infections and 56 deaths. A day later, 2798 people with the virus, 80 dead. Then more than 5000. Six thousand, 132 dead. Seven thousand, 170 dead.
At this stage, fatalities are mostly in the elderly, the young and people with existing respiratory problems. Coronavirus is essentially a viral pneumonia at its worst stage, but is less deadly than SARS. Like flu, there is no magic cure: symptoms are treated with drugs and intravenous fluids.
“We really don’t know where it is going at the moment,” Young says. “Will it plateau out? Will it continue to expand? It will probably be stable enough for a vaccine to be effective over the next few years. There have already been some … mutations within this virus but we don’t believe they are going to impact significantly on the efficacy of the vaccine that we are producing.”
The next fortnight is when we will really see what the world is facing.
On Wednesday, Scott Morrison announced a possible rescue mission for some of the 600 Australians still in Hubei province, but it came with a condition: they will be brought to Christmas Island for a two-week quarantine period.
Authorities are now attempting to strike a delicate balance between public health and overcorrection, especially when the latter can bring disastrous economic consequences.
British Airways this week suspended all flights to China. Hong Kong closed most of its mainland border with China.
Earlier in the week, Professors Gabriel Leung and Joseph Wu of the University of Hong Kong’s faculty of medicine, a WHO collaboration centre for infectious diseases, warned that “substantial, draconian measures limiting population mobility should be taken immediately”.
“Self-sustaining human-to-human spread is already present in all major Chinese cities,” they said in a presentation.
“2019-nCoV may be about to become a global epidemic.”
On Friday, WHO declared the coronavirus was now a public health emergency of international concern.
This article was first published in the print edition of The Saturday Paper on Feb 1, 2020 as "Anatomy of an epidemic".
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