What the genetics of COVID-19 mean for the survival of wild great apes

In 1994, researchers found two chimpanzees dead in Côte d’Ivoire’s Taï National Park, which holds West Africa’s largest rainforest. Autopsies of the chimpanzees revealed signs of hemorrhage resembling those found in humans during outbreaks of ebolavirus that occurred decades earlier in Zaire and Sudan. Indeed, further studies led to the designation of Taï Forest ebolavirus, one of five known strains of the virus that can lead to the ebolavirus disease. One researcher in the park contracted the disease during this time.

This is one of many stories of a zoonotic disease, also referred to as a zoonosis, which is a disease transmitted to humans by animals. Zoonoses are transmitted via direct or indirect contact with an infected individual, consuming contaminated food or water, or through vectors – for example, being bitten by a mosquito carrying the disease.

The focus on transmission to humans dominates the global narrative of zoonoses, which include West Nile, rabies, Lyme and others. But certain pockets of the zoological research community focus on the reverse: humans transmitting zoonoses to wildlife, known as zooanthroponosis or anthroponosis.

In the current case of COVID-19, researchers of non-human primates have sounded alarm bells for the risks humans pose for transmitting SARS-CoV-2, the viral pathogen that causes the COVID-19 or coronavirus disease, to species of primates, including monkeys and apes. Being among some of the world’s most endangered species, of particular concern are wild great apes, including bonobos, eastern and western gorillas, orangutans and chimpanzees.

“These types of outbreaks can have really devastating effects on primate populations,” says says Amanda Melin, a biological anthropologist who runs the Primate Genomics and Ecology lab at the University of Calgary. “This is a great example of the risks that we pose to other animals in the earth.”

So far, there have been no positive tests of COVID-19 in wild great apes – but the deadliness of the disease, should transmission occur, is likely high.

Meet the ACE2 inside of you

“It’s the quickest study I’ve ever been involved in,” says Melin of a study she co-led with Mareike Janiak, a postdoctoral scholar in molecular anthropology, and James Higham, a primate evolutionary biologist at New York University, that helps dispel the guesswork of which non-human primate species are at greatest risk. The study was conducted within about seven days in early April and posted to a preprint server shortly thereafter because of the urgency of its findings, which examine the genetics behind how the SARS-CoV-2 pathogen triggers the COVID-19 disease itself.

In order for a viral pathogen to take hold in a host, the proteins on its surface must bind with certain proteins on the surfaces of a host’s cells. Once the pathogen’s protein has found its cellular protein match, known as a ‘receptor,’ the pathogen can enter the cell and trigger the disease. Coronavirus pathogens – not just of COVID-19, but of other coronaviruses as well – express spike proteins on their surfaces.

“If the virus’s protein can’t find anywhere to bind, then it’s not going to become infectious,” Melin puts simply.

Genes determine which proteins are formed on which cells. Melin’s study examines the coding sequence of the ACE2gene, which codes the cellular protein (the ACE2 receptor) for the SARS-CoV-2 pathogen. These receptors are found in endothelial tissues throughout the body, including in the lungs, hence the disease’s respiratory effects.

As is the case concerning most forms of life, less diversity means less resilience to threat, and so too does it go for genetic predisposition to COVID-19.

Proteins are made of amino acids. Genes can vary in the sequences of their comprising DNA, and the variants of a gene will code protein receptors with different structures of their amino acids. Receptors with a range of structures make it more difficult for a pathogen to find its match.

With that context, consider this statement from Melin’s study: “Here, we show that all apes, including chimpanzees, bonobos, gorillas, and orangutans, and all African and Asian monkeys, exhibit the same set of twelve key amino acid residues as human ACE2.”

In other words, we and many of our primate cousins are in the same boat of being highly susceptible because we have highly similar ACE2 genes and receptors, making it easier for the SARS-CoV-2 pathogen to find its binding match on our cells.

Interestingly, the study found that monkeys in the Americas, and some tarsiers, lemurs and lorisoids, had more ACE2 genetic variation, indicating that many species are likely less susceptible. However, Melin warns, “some lemur species are also likely to be highly susceptible, which is worrying as they are also among the most endangered primates”.  

(Bats, notorious for being hosts and spreaders of coronaviruses, have exceptionally high ACE2 genetic variation. “Within just the handful of bat species that we looked at, we saw genetic variation equivalent to the variation we saw across the entire range of other mammals we included,” says Melin.)

“It’s easy to imagine that we’re closely related to other non-human primates, and so we should be careful with diseases. But knowing that they have the exact same sites and should be equally susceptible to us, and seeing what it’s doing to humans around the world… it’s really concerning.”

Signs of trouble

At the end of 2016 and into early 2017, chimpanzees in the Taï forest were seen with cold-like symptoms. While it did not prove deadly, the illness was found by researchers to have been a coronavirus passed to the chimpanzees from humans, likely poachers.

“Similar to Gombe, disease is the leading challenge for conservation of chimpanzees at Taï,” says Thomas Gillespie, whose work with wild great apes in Africa includes directing the Gombe Ecosystem Health Project, in addition to running the Gillespie Lab at Emory University. “Because of that, we’re always alert to the risk of disease exposure from people. The Taï team, 10 years ago or so, had a major respiratory outbreak that killed all the young chimpanzees”

The tell-tale signs of COVID-19 are likely also the same for human and non-human primates, namely dry cough and fever.

“We expect to see human-like symptoms, or more extreme versions of those. Laboratory-based infection of macaques resulted in similar disease progression to what we’re seeing in humans,” says Gillespie.

Because best practices of wildlife conservation, and especially with wild great apes, demand limited human interaction, researchers rely on technology to check animals for symptoms from a safe and hidden distance. Laser thermometers are used to check fecal masses immediately after defecation to determine body temperatures. Blood meals from mosquitos are tested to keep track of pathogens circulating between them and animals. Carrion flies, which feast on dead animals, can give insights on mortality.

“The Cross River gorillas, for example – we never see them because they’re very cryptic,” says Gillespie of the critically endangered species. Only an estimated 200 or 300 remain, residing at the border of Nigeria and Cameroon. “But the flies are still going to find them. Flies are going to let us know if there’s a spike in mortality. And then that can alert us to potential issues.”

Should COVID-19 begin to be found in wild great apes, there is good and bad news. The bad is that quarantining isn’t an option. Because of group dynamics, individual animals within most groups cannot be removed – “They don’t respond well… it tends to go quite badly,” says Gillespie – making the likelihood of virus spreading to the entire group of a single infected animal quite high.

“And, once a wild animal has left the wild,” he adds, “there are tremendous threats involved with putting them back in the wild because we might have exposed them to additional pathogens in the sanctuary setting.

“So we can’t think about things like darting individuals, removing them from the group, quarantining them. We have to really focus on them not becoming infected. And that’s the most important thing.”

Gillespie nonetheless expects the virus to make its way into at least some populations of wild apes populations. The key now is to understand how it is likely to spread among species, based on exposure as well as the apes’ behavior and ecology. For example, in some places, habituated apes – those accustomed to proximity to humans – might be exposed to SARS-CoV-2, but will likely never come into contact with non-habituated apes. In other areas, this might not be the case.

And in yet other areas, monkeys that share habitats with apes – baboons and vervet monkeys in Africa; macaques in Asia – might spread the virus among great ape groups, or act as intermediaries, carrying the virus from humans to great apes.

“This is something we’re actively working on,” says Gillespie, who is leading a team focused on creating a model of sites across Africa and Asia to guide location-based best practices for ape conservation during the pandemic. “We’re modeling the different ape species, including variables like demographics, behavioral ecology, and proximity to humans and other susceptible species. This can all influence the dynamics of transmission to wild great apes.”

Protein-informed policy

Many protected areas inhabited by wild great apes have quickly developed lockdown measures of their own, such as shutting down tourism, logging and mining operations and extensively testing staff and researchers.

One of the major efforts currently addressing this is led by the Primate Specialist Group and the Wildlife Health Specialist Group, both of the International Union for Conservation of Nature. The two groups released a joint statement in early March, listing ways that humans can minimize risks to wild great apes, including disinfecting their footwear, wearing surgical masks, quarantining when coming from abroad, and immediately leaving an area when feeling the need to cough or sneeze – and not returning.

But for local communities who depend on the use of certain forests, current measures might mean they’re left without a livelihood. To this end, the IUCN has created a task force, which includes Gillespie, focused on COVID-19’s impacts on areas where wildlife and communities share and depend on the same ecosystems. One component of this effort has been distributing funds to communities that might otherwise be forced to resort to actions that could threaten wildlife.

Melin’s and Gillespie’s studies and others like them are proving crucial tools for these conservationists to know where and how to allocate resources to protect species highly vulnerable to the disease, as well as provide scientific backing to policy- and decision-makers about the vulnerability of these species.

Even after the heightened phase of the pandemic has lessened, changes must continue to be made, she says: “For primate observational research, we need to continue to be really careful about quarantining ourselves and about our proximities, always using best practices when we’re interacting with non-human primates. More generally, I hope we can slow and then stop the illegal trade of wildlife, which might help prevent future, different outbreaks.”

And then she broadens her thoughts: “How will it feel collectively, as humans, if we’re responsible for the rapid extermination of these species from the Earth?”