Can a new app predict the next pandemic?

When asked about the possibility of future pandemics, virologists rarely mince words: Another one is coming. It’s just a matter of when.

In fact, there are an estimated 1.7 million viruses that are believed to exist in mammals and birds, and nearly half could potentially follow the deadly trajectory of the coronavirus responsible for the spread of COVID-19—meaning it could jump from animal to human and kick off another pandemic.

Finding ways to prevent that is the motivation driving a team of researchers at the University of California at Davis. They are trying to help the world’s scientists determine how dangerous each one might be by ranking its likelihood of being transmitted between species and evolving into a form that humans could easily pass to one another. This poorly understood phenomenon called “viral spillover” has a long track record in causing outbreaks, including Ebola, MERS, SARS, and HIV, the virus that causes AIDS.

The team has launched a web-based tool appropriately called SpillOver. The app assesses 32 risk factors—such as virus species, host species, and country of detection—to generate a spillover risk score. “We looked at viruses known to be transmissible from animals to human and those that were newly discovered,” says Zoe Grange, who worked on the project as a postdoctoral wildlife disease ecologist at Davis. By flagging so-called “viruses of concern,” the publicly available database is intended to create a watchlist for scientists and policymakers.

Grange and her advisor, Jonna Mazet, an epidemiologist at the UC Davis School of Veterinary Medicine, came up with the idea of a ranking tool during a beach walk in the spring of 2017. Grange says, “we asked, ‘Why can’t we create a credit report for viruses?’”

The tool is an attempt to make sense of a surge of reports of new animal virus sequences that were collected as part of the of the $238 million PREDICT project run by the United States Agency for International Development between 2009 and 2019. In a prescient pre-COVID 19 recognition of the threat of wildlife viruses, the program created a global army of 6,800 virus hunters in 35 countries. Some workers collected blood, saliva, urine, or feces from bats, rodents, and primates, while others analyzed the genetic sequences of those samples.

They discovered nearly 900 new viruses, including 160 coronaviruses and a previously unknown strain of Ebola. They also detected 18 previously known zoonotic viruses, such as Lassa and Marburg, which cause hemorrhagic fevers. “We discovered a lot of viruses. But what does that tell you?” says Grange, who now is lead health protection scientist at Public Health Scotland. “Not every virus will cause a pandemic.”

The SpillOver database is configured so that researchers can add their own reports. “We wanted to make a tool everyone can use. They can add their virus discoveries and do their own rankings,” Mazet says.

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In a study published this week, researchers led by Grange and her team at UC Davis used data from nearly 75,000 animals as well as public records of virus detections to rank the spillover potential of 887 wildlife viruses. SARS-CoV-2, which is the virus behind COVID-19, came in second place for its likelihood to cause disease and spread within human populations. Although the data was based on limited reports of the virus in zoo tigers, lions, and mink, it served as proof that the ranking tool worked. Now, the World Health Organization believes that SARS-CoV-2 likely spread to humans either directly from a bat to human, or via an intermediary animal, such as a pangolin. The top-ranked virus was Lassa, which is endemic in the rodent population of West Africa and causes hemorrhagic fever, which kills 1 percent of victims.

Rising threat of spillover

Unlike other tools that assess the risk of a limited number of viruses, such as influenza, this database focuses on viruses found in wildlife from 26 virus families. It’s a welcome resource for the field because the pace of spillover is accelerating, says Raina Plowright, a wildlife ecologist at Montana State University who studies disease dynamics between human and animal populations.

“What I like is that they’re thinking very broadly about the risk factors, in particular the stresses on the ecosystem where the reservoir host resides and the potential interaction that humans have with these hosts,” she says. “We’re intruding into the last wild spaces and coming into more contact with wildlife and taking away key resources that animals need to survive.” When animals’ habitat is limited, they’re forced into more populated areas in search of food. Just like humans, when animals are stressed, they’re more vulnerable to getting sick and spreading viruses—among their species, to other animals, and potentially to humans.

What’s unknown is how some of these new viruses might infect humans, a complex sequence that involves a pathogen entering human cells, multiplying, and spreading in the body while evading the immune system. While some viruses, such as the Nipah virus, can be passed from bat to humans, other viruses need to go through an adaptation process to become contagious.

“Typically a virus needs multiple mutations to be transmissible to humans,” says Hector Aguilar-Carreno, a virologist at Cornell University College of Veterinary Medicine who studies viral immunology. “It will depend on the virus. In some cases, you might need one or two mutations. But some might need 20 or more to undergo the necessary steps to be transmissible or to replicate in the host.” Complicating the issue further is whether these mutations need to happen through a third-party animal, as has been suggested with SARS-CoV-2. The virus would have changed when it possibly jumped to a pangolin and then again when it jumped to humans.

The value of watchlists

The slipperiness of such potential spillover events begs the question: What should we do with all this information? According to Mazet, who was principal investigator at PREDICT, the data puts high-risk viruses on policymakers’ radars. “We created this tool because we didn’t just want to scare the world that there are a bunch of new viruses and no one knows what to do with them,” she says. “The tool is to create watchlists for surveillance with all the data about how people are exposed.”

One possible scenario: Given that bat-borne diseases can be transmitted through guano (in which coronavirus RNA has been detected), farmers who collect guano for fertilizer might be advised to use personal protective equipment or disinfect guano. “We may need to talk about alternative kinds of livelihoods if it’s too dangerous or find new safe practices,” Mazet says. One outcome of the PREDICT project was the creation of book titled “Living Safely with Bats”—the animal most implicated in viral spillover events—that was translated into 12 languages and presented at hundreds of public meetings in Africa and Asia.

Bats who love date palm sap

When epidemiologist Emily Gurley worked in Bangladesh in the early 2000s, her team was able to use specific information about the bat transmission of Nipah, a deadly virus with no known treatment, to help villages reduce their risk. After puzzling outbreaks of Nipah, Gurley and her colleagues traced the virus back to fruit bats. (Before then, the virus had been transmitted to humans in Malaysia through sick pigs.) In many areas of Bangladesh, drinking fresh date palm sap is considered a delicacy; it turned out that bats loved to lick the stream of sap as it flowed into collection pots—and in the meantime contaminated the supply through urination or defecation.

“From this spillover pathway, we set out the evidence that it was the predominant route of transmission,” says Emily Gurley, who’s now an associate scientist at Johns Hopkins Bloomberg School of Public Health. Their efforts led to a “drink safer sap” public education campaign advising villagers to install netting to keep bats away from the collection pots.

Although the PREDICT program ended in September, Mazet says its goal was to build countries’ capacities to continue such surveillance and engage local communities before the next spillover—and possibly next pandemic—take place. A second initiative is focusing on educating a pipeline of health professionals in multiple disciplines at universities in Africa and Southeast Asia to focus on disease prevention and detection. “There are thousands of viruses yet to be discovered,” she says.