London: Developing a vaccine or a treatment for a newly discovered virus is a painstakingly slow and detailed endeavor. Finding a compound that works, testing it in animals, and then rolling it out to clinical trials in humans can take years. And even the top experts in virology and epidemiology typically toil in obscurity, spending long, lonely hours in the lab and garnering fleeting interest only when an unknown ailment sparks headlines. The novel coronavirus has changed all that.
“I’ve got 57 million things to do at once,” says Sarah Gilbert, an Oxford University researcher who devised a vaccine considered one of the frontrunners to stop the outbreak. Like other leading lights in the battle to contain Covid-19, she’s short on sleep and time as she cobbles together funding and fields calls on how to quickly get the vaccine into production.
Gilbert is one of the heroes of the current crisis, scientists who are racing against a virus that’s sparking fear and havoc across the globe. From Asia to Europe, North America, and Africa, infectious disease experts are trialing vaccines, developing new tests for the virus or devising innovative public health strategies to control the outbreak. This is a story about the people working flat-out to save us from the pandemic.
The tale begins in China, where doctors and scientists played pivotal roles in alerting the world about what would come to be called Covid-19. Few deserve more credit for sounding the alarm than Ai Fen, head of the emergency department at Wuhan Central Hospital. On Dec. 30, she received a lab report on a patient with unexplained pneumonia. Ai says she broke out in a cold sweat as she circled the words “SARS coronavirus” in red ink.
After notifying her superiors and warning fellow doctors to take precautions, she sent screenshots of the report to her old medical school classmates. “If I had known how this was going to play out, I wouldn’t have worried about being reprimanded,” she told the Chinese magazine Renwu. “I would have spread the word everywhere.”
Even so, Ai’s report ricocheted among doctors in the city, ending up with Li Wenliang, the 34-year-old ophthalmologist who became known as the Wuhan whistleblower. He began alerting the public about the dangerous virus spreading in the city even as Chinese officials insisted there was no human-to-human transmission. He died in February after becoming infected, prompting a wave of criticism of how China handled the outbreak.
“I’m not a whistle-blower,” Ai told Renwu. “I’m the one who distributed the whistle.” A senior hospital supervisor scolded her for “spreading rumors” by sending texts to other doctors about the virus. Chinese censors have attempted to erase her interview from the internet but bloggers have captured and reposted it. She didn’t respond to requests for comment.
While Ai was putting fellow doctors on alert, researchers in Shanghai led by Zhang Yongzhen were studying a specimen from a patient from Wuhan with an unexplained fever. Zhang’s team concluded the specimen was a novel coronavirus similar to SARS. They started sequencing the complete genome of the virus, which was published on Jan. 11 at virological.org by Edward Holmes, a virologist at the University of Sydney who is part of Zhang’s consortium. Zhang, a researcher at Fudan University, declined to comment.
With the genome’s release, infectious disease experts worldwide pounced on the code in a rush to understand how quickly this new pathogen might spread and how deadly it might become.
Gilbert runs the emerging pathogens program at Oxford’s Jenner Institute, named after the physician who invented the smallpox vaccine in the 18th century. When she heard about the novel coronavirus spreading in China around the New Year holidays, the immunologist had a sense of what might be at stake. She’d been overseeing clinical trials of a vaccine against another coronavirus that causes respiratory pneumonia and sparked a global public health crisis in 2014—Middle East respiratory syndrome (MERS). When it first emerged, MERS looked exceptionally dangerous, killing about a third of those infected. But while it spread to 27 countries and more than 850 people died from the virus, it isn’t as easily transmitted as the virus that causes Covid-19.
Last year, as the new virus emerged in China, Gilbert was starting a second set of human trials in Saudi Arabia for a MERS vaccine, showing it was safe and triggered an immune response. “We know it works in a monkey,” Gilbert says. “It wasn’t clear whether it was effective in humans because there weren’t enough MERS cases to find out.”
That won’t be a problem for the current outbreak, which has infected more than a half-million people worldwide. As soon as the Shanghai scientists released the genetic sequence for the virus, Gilbert’s team began making a vaccine against Covid-19 to test in mice, using the same technique she used for the MERS vaccine: The spiked protein of the coronavirus is added to an adenovirus—a harmless carrier—to make a vaccine that stimulates an immune response to protect the body.
Gilbert was one of several researchers who responded to a call from the World Health Organization in 2015 to propose methodologies for developing vaccines against Ebola, MERS, and a clutch of other more obscure but terrifying sounding illnesses. The WHO’s list also included “Disease X”—that unknown pathogen lurking around the corner waiting to spark a global pandemic. Gilbert proposed her team’s platform, which allows researchers to rapidly respond to new diseases as they emerge. “We can go from sequence to vaccine in a very short space of time,” she says.
Gilbert’s Covid-19 vaccine is one of roughly three dozen in development around the world. While they all have their strengths and weaknesses, and some are farther along than others, scientists say it’s a good thing to have so many competing ideas, because any of them risks being quickly shut down if safety concerns emerge.
One thing all the teams share is a thirst for cash, which is always in short supply. In February, the Coalition for Epidemic Preparedness Innovations, a group in Oslo founded in 2017 to fund vaccine development, gave Gilbert money to produce enough vaccine for small-scale tests. Then on March 24, Gilbert’s team won a 2.2 million-pound ($2.7 million) grant from the U.K. government to help pay for clinical trials on humans, expected to begin in April.
“We’re working around the clock,” she says. “We have a lot of plans to develop.”
While it will likely be a year or more before a vaccine is ready, there’s growing hope that drugs to treat Covid-19 patients could ease the effects of the disease. Scientists are closely watching clinical trials led by Andre Kalil, a 54-year-old physician specializing in pneumonia at the University of Nebraska Medical Center.
The Brazilian-born infectious disease specialist is overseeing the first U.S. clinical trials to determine whether an experimental drug called remdesivir might help patients suffering from the coronavirus. The trial, with more than 100 patients at dozens of hospitals, will yield initial results in another week or so, but for now even Kalil doesn’t know which patients are getting the drug or only standard supportive treatment.
“My hope is that this could be a game-changer, but as a clinician and scientist I have no means to know if this drug is working or not,” he says. “That’s the only way to do good science.”
As soon as Kalil saw the reports about coronavirus in China in January, he and his team began investigating potential therapies, thinking: “We’ve got to start preparing ourselves for the worst.”
That led them to remdesivir, first developed by Gilead Sciences Inc. for Ebola. Though it had proved disappointing as an Ebola treatment, remdesivir had been studied in animals against other coronaviruses, such as SARS and MERS. “The data is compelling,” he says. “But each bug is so different.”
In February, Nebraska Medical Center’s Biocontainment Unit received the first patients returning to the U.S. from the Diamond Princess, a cruise ship that had been quarantined off Yokahama, Japan, after a coronavirus outbreak. An American from the ship was the first volunteer for the trial, and now Kalil’s team is enrolling new patients every day as the virus spreads in the local community. The hospital is treating Covid-19 patients on two floors, and Kalil and his staff regularly check their own temperatures to make sure they’re not becoming infected themselves. “It’s going faster than I predicted,” he says. “It’s a race against time.”
Like many experts on infectious diseases, Kalil says he learned important lessons from the Ebola outbreak in 2014-2016. While the outbreak claimed thousands of lives and lasted almost two years, scientists didn’t have enough time to complete rigorous studies designed to prevent bias—randomized trials in which neither doctors nor patients know who’s getting the drug or a placebo—or they ignored those vital controls altogether.
“What did we learn?” Kalil says. “We learned absolutely nothing in terms of new therapies. We cannot afford to repeat this.”
Kalil worries that the same mistake could be made today as doctors worldwide hand out untested treatments without the rigor of clinical trials. That includes chloroquine, the anti-malarial drug, and HIV antivirals lopinavir and ritonavir, both of which have been used to treat Covid-19 patients but can be toxic and haven’t been approved for use against the novel coronavirus.
“If these drugs can be helpful to clear the coronavirus that’s great news, but you will never know unless you do a randomized, controlled trial,” he says. “We have to offer our patients real science. It’s the only way to help them.”
For the man leading the coronavirus response at the World Health Organization, the fact that scientists such as Kalil have to rush testing potential new therapies is a travesty. Why, he asks, wasn’t this done years ago, and why do we have so few effective antiviral drugs?
“It’s almost laughable given the scale of the perceived threat,” says Michael Ryan, the head of the health emergencies program at the UN agency. “We’re still going back to the same old drugs we’ve been using for 20 years now.”
It’s Ryan’s job to wrangle the WHO’s 194 member-states into developing treatments and stockpiling resources to prepare for a pandemic during times of calm. The world spent about $1 billion to stop the Ebola epidemic in the Democratic Republic of Congo last year, but the surrounding countries have only gotten a fifth of the $65 million they requested from wealthier nations to prepare for the next outbreak.
“When the crisis strikes, you react and say, why didn’t I do something about this before?” he says. “That’s the human condition. But the reality is, the price we pay for that as a society is very high.”
But the political agendas of wealthier countries—which contribute the bulk of the WHO’s funding—can trump the agency’s recommendations. With little enforcement power and a history of not standing up to governments during health crises, the WHO is frequently derided as toothless.
The criticism comes from all sides. When Ryan and WHO director general Tedros Adhanom Ghebreyesus praised China for its “laser focus” approach to tackling Covid-19 in January, critics attacked them for sounding like Beijing’s pawns. Then six weeks later, he came under fire for a veiled criticism of governments that respond slowly. “Speed trumps perfection,” Ryan said during a March 13 press conference. “Be fast. Have no regrets.”
Ryan has little patience for such debates, insisting that countries must pursue aggressive contact tracing to contain the outbreak. He has understood the importance of quick, decisive action since the first emergency he faced, an outbreak of Ebola in Gabon in the 1990s.
“In a crisis, you don’t have the luxury of time, and you have to accelerate decisions uncomfortably,” he says. “You won’t always be right. You will always have to make a decision before you have enough data.”
Ryan never planned a career in public health. Trained as a trauma surgeon, the Irishman got a short-term contract in 1990 to help teach doctors in Iraq. While there, he broke his back in a car crash, which made it difficult for him to spend the long hours on his feet required of a surgeon.
He retrained in epidemiology and joined the WHO in 1996, where he has coordinated the agency’s reaction to SARS, fought Ebola, and steered the response to the H1N1 flu pandemic. After a failed push to get the organization to put more resources into emergencies and epidemics, he left in 2011 to work on polio eradication. When Ghebreyesus was appointed director general in 2017, he brought Ryan back to head up the group’s emergency response effort after it had been widely criticized for being too slow to respond to Ebola to the 2014-2016 Ebola outbreak.
Ryan is confident a vaccine will eventually be developed and new therapies will be found, but he worries whether those will be available to everyone in need.
“I won’t be happy if we get a good vaccine and only people who can afford to pay for it get it,” he says. “That would be the great tragedy.”
That’s a tragedy that threatens to unfold in Africa, where fragile health systems and a population already battling malaria, HIV, and Ebola make Covid-19 all the more dangerous. The virus has been slow to reach Africa, but the continent of 1.2 billion people has more than 4,200 cases in 46 countries, and many more have likely gone undetected.
In the vanguard of Africa’s effort is Amadou Alpha Sall, a 50-year-old infectious disease expert who leads the Senegal branch of the Institut Pasteur, a global research center. In January, as Sall started hearing about the mysterious pneumonia in China, he began thinking, “Let’s get ready.”
On Feb. 27 Nigeria confirmed the first case in sub-Saharan Africa. Four days later—the day Senegal reported its first infection—Sall was summoned to a meeting at the presidential palace with top government officials and disease experts. Around the same time, the WHO asked Sall’s group to run one of two key labs coordinating tests across the region.
Since then, Sall, who studied virology and public health in France and Britain and has advised governments worldwide on outbreaks, has been working 18-hour days with colleagues from across Africa. “I don’t sleep that much,” he says.
Health authorities hope the continent’s experience with Ebola will help tackle the coronavirus. After Ebola hit neighboring Guinea in 2014, Sall’s team was one of the first on the ground to oversee testing, a crucial part of the response. The epidemic overwhelmed the region, killing more than 11,000 people and hindering treatment of other diseases, but Sall says Africa is in a stronger position this time around.
“At the highest levels, people are much more aware and they are reacting quickly,” he says. “That doesn’t mean it’s going to be perfect, but it’s going to be much better.”
Ebola also underscored the need for Africa to build its own capacity to respond to emergencies. There was no Ebola vaccine in time to help the people of West Africa, but one was deployed in the Democratic Republic of Congo in 2018 following a new outbreak.
With a partner in Britain, Sall is developing a test for Covid-19 that can yield results in as little as 10 minutes, rather than the hours it takes today. Though cost remains a barrier, he aims to make it affordable even for countries with vulnerable health systems. And his testing technology is designed to work for other illnesses that will surely emerge, spurred on by climate change, increasingly mobile populations, and antibiotic resistance.
“We are going to be living in an era of epidemics coming regularly,” he says. “This is going to be our way of life.”
Amid efforts across the world to face down Covid-19, Singapore’s success in keeping a lid on the virus offers a model for containing an outbreak. It only reported its first deaths from Covid-19 on March 21, almost two months after the virus arrived in the city-state. While cases doubled in the last week to 844, mostly due to travelers returning home, the country’s coronavirus testing has been among the world’s most aggressive. As of last week, Singapore had conducted more than 39,000 tests, a higher rate per capita than South Korea, widely seen as having succeeded in driving down cases through extensive checks.
As executive director of the National Centre for Infectious Diseases, Leo Yee Sin is helping steer Singapore’s response, deploying lessons learned while combatting SARS in 2003 and H1N1 in 2009. In early January, as reports of the virus began emerging from Wuhan, she immediately began preparing, knowing it would inevitably be headed her way given the extensive links between China and Singapore.
“SARS arrived in Singapore without us realizing it,” says Leo, 60. “With Covid-19, the distinctive difference is we saw it coming.”
Before the first case was discovered in Singapore on Jan. 23, her center had already developed its own test for the virus and began ramping up its capacity for mass assessments. Singapore can administer more than 2,000 tests daily and is working to expand that.
The first patients who tested positive received treatment at Leo’s center, where researchers immediately began studying the virus. Leo hoped that, as with SARS, infectious coronavirus patients would show symptoms that would make them easier to spot and quarantine before they transmitted the disease. She soon understood she was dealing with something altogether different.
“Patients can transmit the virus very early on,” she says. “Viral shedding, to our surprise, was highest at the early stages of illness and decreases as the disease progresses.”
She used that early research to advise a strategy shift for Singapore’s Ministry of Health, recommending that physicians offer five days of medical leave to anyone showing signs of respiratory distress so they could stay at home and not spread the sickness.
Singapore’s tactic of aggressively testing while tracing and isolating contacts of infected people has worked in part because Leo’s center has a place to quarantine patients. Just over a year ago, her team began moving into a new 14-story building with 330 beds devoted to treating infectious diseases.
“We count ourselves very lucky that we have a new building just in time for this mobile pathogen,” she says. “We joke among ourselves that it’s a very expensive building and very costly to maintain, but the investment has returned more than we hoped.”
With its population of 5.7 million, Singapore may not be easy for larger countries to copy. So far it’s managed to limit transmission without draconian measures such as shutting down schools or shopping malls, but it has announced the closure of bars and cinemas as cases continue to rise.
“We anticipate this is only the beginning of the epidemic,” Leo says. “The best thing to do in terms of school closures and social distancing is when the epidemic is about to hit the peak. Nobody has a crystal ball to pinpoint when that will be.”-Bloomberg
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