After COVID-19, how we can prepare for a new pandemic

As the world reels from the worst pandemic in a century, scientists are calling for new warning systems, tools to track the emergence of exotic pathogens and a battery of anti-viral drugs.

Staff applaud as a masked nurse carries baby Amine Tepe, who was diagnosed with COVID-19 when she was 37 days old, as she is taken out of the intensive care unit at an Istanbul hospital this week. Picture: AP

The virus hunters had spent five years tracking down their quarry, a colony of horseshoe bats teeming with an ominous collection of coronavirus strains.

In a single cave in the Chinese province of Yunnan a team of researchers found inside these small mammals all the genetic building blocks of SARS, a virus closely related to COVID-19 that killed nearly 800 people in 2003 while causing economic mayhem across Asia. They warned that all the elements were in place, as they presented their findings two years ago, for a new SARS-like disease to skip again from animals to humans.

As the world reels from the worst pandemic in a century, scientists are calling for new systems that react to these kinds of warnings.

They argue that we need new tools to track the emergence of exotic new pathogens and a battery of new anti-viral drugs to treat them. A pharmaceuticals industry incentivised to develop treatments for the rich world’s non-infectious diseases — diabetes, heart disease and dementia among them — should be nudged towards new priorities. Pandemic plans focused on influenza must be rewritten, experts say, while still recognising that the world is overdue a cataclysmic flu pandemic.

An Indonesian medic takes a blood sample from a woman during a rapid test in Surabaya. Picture: AFP

“We need to get on a completely different footing now,” says Sir John Bell, regius professor of medicine at Oxford. “This has been a wake-up call”.

Vincent Racaniello is a professor at Columbia University, New York, and a host of the podcast This Week in Virology. He’s one of many experts who say we need to gather better intelligence on our formidable microbial foes.

“The first thing people need to understand is that every virus that you can think of that infects people — polio, measles, herpes, chickenpox — they all came from animals,” he says.

He might also have added influenza, ebola and HIV/Aids.

He supports the creation of a new global atlas of zoonotic pathogens, a catalogue of the bugs that exist in other species that have the potential to spill over into the human population. Researchers would use it, in part, to develop “plug and play” vaccine technologies that could rapidly be modified to counter new threats.

The idea already has a price tag attached: the Global Virome Project, which plans to identify 70 per cent of the estimated 1.6 million potentially zoonotic viruses over 10 years, is projected to cost between up to $5.3bn. Given the trillions being spent to prop up the global economy, Racaniello suggests that constitutes good value.

A monk walks in front of a giant Buddha statue wearing a face mask at Wat Nithet Rat Pradit temple in Pathum Thani outside Bangkok. Picture: AFP

A new institute being founded at Oxford University will have similar goals. The Pandemic Preparedness and Vaccine Research Centre, a collaboration with the drugmaker Astrazeneca, aims to become a global sentry. It will evaluate techniques for screening blood transfusions around the world, to search for the genetic signatures of ominous novel pathogens, and it will seek to galvanise research into anti-viral treatments and diagnostics.

“It’s an interesting space academically, but also, ultimately I think, commercially,” says Bell, one of the driving forces behind the project.

It also plans to monitor for signs of unusual illnesses, across Africa, Asia and the Indian subcontinents, and it will look at tracking zoonoses, diseases that can be transmitted to humans from animals.

Bats, Racaniello says, are an obvious starting point. They are abundant, accounting for a fifth of all mammals. They thrive across a vast range of habitats, individuals often cover large distances and they harbour an extraordinary range of viruses.

“We’ve barely scratched the surface of asking what viruses bats have and which ones are a threat to people,” he says.

The effort would have to cover other animals too. SARS and COVID-19 are thought to have leapt from bats to humans via intermediary “amplifier” species.

Mice carry the dangerous hantaviruses; dromedary camels harbour MERS, another coronavirus that kills a third of the humans it infects; HIV/Aids, which has killed 32 million people since 1981, came from chimpanzees. And as a growing human population continues to clear wild areas we will, inevitably, brush up against more novel microbes.

“Even our pets can be infected with influenza and I hear that dogs have become popular in China,” Racaniello says. “Suddenly there are millions and millions of dogs. We are worried that they’re going to be the source of the next influenza pandemic.”

Influenzas are particularly tricky customers, largely because of how two entirely separate strains can swap genetic material if they cross paths in a single host. Once in the lungs of a mammal, an avian strain can “reassort,” or mix genes, with any human influenza viruses that are also present. This can lead to an entirely new viral strain, capable of sustained human-to-human transmission. If this virus has not circulated before, the entire global population will be susceptible.

Plastic partitions separate children at lunch time at a kindergarten in Yongzhou in China's central Hunan province. Picture: AP

“That’s the worry. That a dog would be infected with two different influenza viruses, one human and another from the faeces of a bird,” Racaniello says. “They make a new virus, which then makes the jump to the pet’s owner and it takes off.”

The point of cataloguing animal viruses is to build weapons against them. One focus could be on so-called pan-viral treatments, medicines that have the potential to be effective against a range of pathogens.

Some of the most promising candidates so far have come from screening drugs originally created for different purposes. This is how Remdesivir came to prominence. It was originally developed to treat hepatitis C and later tested against ebola, but with disappointing results. Last month, however, it became the first treatment to show signs, in a high-quality trial, of working against COVID-19.

Broadly speaking, anti-viral drugs are tricky to make because viruses replicate by hijacking the machinery of our cells. A drug that clogs up that machinery might destroy the virus, but there is a very good chance that it will harm the human host as well.

Relatives prepare the burial a COVID-19 victim at a graveyard in New Delhi, India. Picture: AFP

With remdesivir, we may have got lucky. It inhibits a so-called polymerase enzyme — a compound that the coronavirus uses to assemble new copies of its genetic code. Human cells also use polymerases, but the drug leaves them alone.

The way in which they co-opt our biology mean that viruses have very few weak points of their own. However, Racaniello argues that the main obstacle to the development of an effective coronavirus treatment has been a lack of funds.

“We could have had a drug to block every coronavirus years ago,” he says. “But we got complacent after SARS. And people don’t want to spend the money — companies don’t want to invest when they don’t see a bottom line. And we’re at the mercy of that short-sightedness.”

Dr Andrew Preston, reader in microbial pathogenesis at the University of Bath, agrees that drugmakers have not made dealing with pandemics a priority.

“You’re asking people to develop a drug that hopefully is going to get used very rarely,” he says. “And if it’s really good, it’ll be used over a relatively short course and then not used again.”

Investment is instead skewed towards treatments for chronic diseases such as diabetes, which tend to be taken daily and for a lifetime. One story that’s often cited involves the drugmaker Gilead. After it announced a potentially revolutionary hepatitis C drug, its share price dropped: by curing patients it was destroying its market.

Italian violinist Fiamma Flavia Paolucci performs at Tor Vergata Hospital in Rome. Picture: AFP

Research by Dr Michael Head, of the University of Southampton, suggests that funding decisions for infectious disease research are overwhelmingly reactive. Coronaviruses accounted for as little as 0.1 per cent of spending on disease research between 2000 and 2020. More than 40 per cent of all coronavirus funding over the past 20 years has been awarded in the past four months.

Head is among those calling for a more long-sighted approach. “The inter-pandemic period is the time to prepare,” he says. The aim, he adds, is to avoid the “reactive, running-around-screaming we have at the minute, where we’re all trying to do our best in very difficult circumstances”.

Oxford’s new pandemic preparedness centre would work in several fields, Bell says.

“First will be surveillance — so understanding what’s out there and when it’s coming.”

The university already has tropical medicine partners across the world. The centre will seek to link them into a surveillance network. Alarm bells should sound, for instance, if a cluster of pig farmers in Indonesia suddenly fall mysteriously ill.

It will also start to evaluate new ways of surveilling threats, such as analysing blood transfusions from around the world, searching for suspicious genetic sequences.

Groom Vitthal Koditkar. left, of Hirpodi village speaks with his bride, Vrushali Renuse, of Pabe village and family members after their wedding during lockdown in the Pune district of India. Picture: AFP

Will the investments pay off? The contours of the post-lockdown world are unknown but scientific consensus is rock solid on one point: COVID-19 will not be the last virus to sweep the planet.

Over the past 300 years, there have been 10 influenza pandemics and avian flu outbreaks have bubbled away since 2003.

“None of them has yet gone on to develop the person-to-person spread which would make it the killer that we all fear,” Preston says.

In 2009, however, a swine flu epidemic highlighted the limits of the World Health Organisation’s existing monitoring systems. And we have now seen three coronaviruses in three successive decades — SARS in 2003, MERS in 2012 and COVID-19. Bigger cities, global travel, intensive animal farming, a rising human population — all will increase our vulnerability.

As the science writer David Quammen put it, “zoonosis”, the term for an animal infection transmissible to humans, is “a word of the future, destined for heavy use in the 21st century.”

The Times