Future pandemics—and suffering of the kind inflicted by COVID-19—could be avoided if we troubled ourselves to see where dangerous pathogens lie in wait. We could, two unrelated studies suggest, save ourselves untold woe and conserve our fortunes if we were to look into matters geographic, zoologic, and genomic. More specifically, we need to keep our eyes wide open when we venture into the planet’s last wild places. There, we may run into wild animals that are infected with pathogens harboring wild genetic traits—which is to say, genetic traits that evolved naturally, beyond our gaze, and that waited patiently, perhaps decades, for a chance to strike.

Recognizing the potential for outbreaks

According to an international research team of Chinese, European, and U.S. scientists, the SARS-CoV-2 lineage responsible for the COVID-19 pandemic has been circulating in bats for 40–70 years and likely includes other viruses with the ability to infect humans. This finding, which is derived from a newly constructed evolutionary history of SARS-CoV-2, has implications for the prevention of future pandemics stemming from this lineage.

To put together SARS-CoV-2’s evolutionary history, the scientists had to account for recombination events, which occur frequently in coronaviruses and which complicate inquiries into a pathogen’s origins.

“Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus’s genome can be derived from multiple sources,” explained Maciej Boni, associate professor of biology at Penn State and the lead author of a study that appeared July 28 in Nature Microbiology. “This has made it difficult to reconstruct SARS-CoV-2’s origins. You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution.”

The study, titled “Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic,” described how the team used three different bioinformatic approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. The article also detailed how the team reconstructed phylogenetic histories for the nonrecombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past.

“We find that the sarbecoviruses—the viral subgenus containing SARS-CoV and SARS-CoV-2—undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China,” the article’s authors wrote. “SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination.”

The authors maintained that the results generated by the three bioinformatic approaches were consistent with Bayesian evolutionary rate and divergence date estimates as well as with two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. In addition, the authors estimated that divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000), and 1982 (95% HPD: 1948–2009).

These findings led the scientists to conclude that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. The scientists added, “The unsampled diversity descended from the SARS-CoV-2/RaTG13 common ancestor forms a clade of bat sarbecoviruses with generalist properties—with respect to their ability to infect a range of mammalian cells—that facilitated its jump to humans and may do so again.”

The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the spike protein, which enables the virus to recognize and bind to receptors on the surfaces of human cells.

The team emphasized that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.

“The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans,” said the article’s senior author, David L. Robertson, PhD, professor of computational virology, MRC-University of Glasgow Centre for Virus Research. “We should have been better prepared for a second SARS virus.”

“We were too late in responding to the initial SARS-CoV-2 outbreak,” added Boni, “but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits.”

Investing in prevention

A surveillance system of the kind suggested by Boni is in line with recommendations from another recent study, one that argues for investments in preventive efforts. The study, prepared by scientists from Boston University, Princeton University, Duke University, Conservation International, and other institutions, indicated that “preventive efforts would be substantially less than the economic and mortality costs of responding to these pathogens once they have emerged.”

The scientists assessed the cost of monitoring and preventing disease spillover that is driven by the unprecedented loss and fragmentation of tropical forests and by the burgeoning wildlife trade. They discovered that significantly reducing transmission of new diseases from tropical forests would cost, globally, between $22.2 and $30.7 billion each year.

In stark contrast, they found that the COVID-19 pandemic will likely end up costing between $8.1 and $15.8 trillion globally—roughly 500 times as costly as what it would take to invest in proposed preventive measures. To estimate the total financial cost of COVID-19, researchers included both the lost gross domestic product and the economic and workforce cost of hundreds of thousands of deaths worldwide.

These findings appeared in Science, in a policy brief titled, “Ecology and economics for pandemic prevention.” The brief emphasized that “we invest relatively little toward preventing deforestation and regulating wildlife trade, despite well-researched plans that demonstrate a high return on their investment in limiting zoonoses and conferring many other benefits.”

For decades, scientists and environmental activists have been trying to draw the world’s attention to the many harms caused by the rapid destruction of tropical forests. One of these harms is the emergence of new diseases that are transmitted between wild animals and humans, either through direct contact or through contact with livestock that is then eaten by humans. The SARS-CoV-2 virus—which has so far infected more than 15 million people worldwide—appears to have been transmitted from bats to humans in China.

“Much of this traces back to our indifference about what has been occurring at the edges of tropical forests,” said Les Kaufman, PhD, one of the article’s co-authors and a Boston University professor of biology.

To reduce disease transmission, Kaufman and his collaborators propose expanding wildlife trade monitoring programs, investing in efforts to end the wild meat trade in China, investing in policies to reduce deforestation by 40%, and fighting the transmission of disease from wild animals to livestock.

The researchers also propose to increase funding for creating an open-source library of the unique genetic signatures of known viruses, which could help quickly pinpoint the source of emerging diseases and catch them more quickly, before they can spread.

“The pandemic gives an incentive to do something addressing concerns that are immediate and threatening to individuals, and that’s what moves people,” argued Kaufman. “There are many people who might object to the United States fronting money, but it’s in our own best interest. Nothing seems more prudent than to give ourselves time to deal with this pandemic before the next one comes.”

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