IN THE FIELD OF epidemiology, an “spillover” is a virus that has jumped from one host species to another. The fallout of most concern to humans is that of other animals on Homo sapiens. These can then create “zoonotic” human diseases, of which covid-19 is believed to be a part (the original host of SARS-CoV-2 is believed to be a bat species as yet undetermined).
However, such traffic can be carried out in both directions. For example, in 2020, the World Health Organization reported that SARS-CoV-2 had spread in Denmark from humans to farmed mink and then passed from animal to animal to create a separate veterinary epidemic. And, earlier this month, an article posted on BioRxiv, an electronic host for work that has yet to be peer reviewed, presented evidence that the virus also circulates in white-tailed deer in North America, presumably having overwhelmed people there. This all adds up to reports suggesting that pets, especially cats and dogs, can also catch SARS-CoV-2 – and in the case of cats at least, then pass it on to others of their kind. .
The fallout of this type is potentially serious for two reasons. The first is that they create viral reservoirs beyond the easy reach of medical science and surveillance. Even if there are no human cases of covid in an area, such animal reservoirs mean SARS-CoV-2 can still lurk, waiting to spread into people. The other is that exposure to the immune system of new hosts can lead to the evolution of new and (if they then reverberate) potentially threatening strains of the virus. The mink incident therefore led the governments of Denmark, the Netherlands and Spain to slaughter 18 million animals and impose strict closures in the areas around the affected fur farms. Treating a wild population, such as white-tailed deer, in the same way would be more difficult. But precautions are still possible. Educating those who interact with deer, such as hunters, can go a long way.
These are, however, reactive approaches. A proactive approach would try to establish which species are most at risk of becoming reservoirs for SARS-CoV-2 before they actually do. This would allow threats to be monitored before they get out of hand. And, as she reports this week in the Acts of the Royal Society, Barbara Han of the Cary Institute of Ecosystem Studies, an independent environmental research organization based in Millbrook, New York, thinks she has found a way to do this.
Starting in early 2020, just after the emergence of covid, Dr Han and colleagues focused their attention on ACE2, a cell membrane protein that was identified early in the epidemic as the point of entry of the virus. ACE2’s daily job is to help regulate blood pressure, and most vertebrates have it in one form or another. The researchers wanted to determine in which other vertebrate species SARS-CoV-2 could bind as strongly to local ACE2 receptors as to those in humans. These would be candidates for the role of reservoirs.
To that end, they gathered molecular information on every version of ACE2 they could get their hands on. Most of them were mammals, 142 of which were species. They then used computer modeling of the interatomic forces involved to determine the strength of the bonds likely to develop between the SARS-CoV-2 spike protein and each version of ACE2. As expected, based on news that broke while they were doing their work, the connection with Mink ACE2 was particularly strong. They found an equally strong affinity with ACE2 in white-tailed deer, long before any reports of infections in this species emerged. Cats and dogs were also found to be at risk, which the data later confirmed. And gorillas and macaques, which have suffered a few cases in zoos, also seemed susceptible.
As useful as this information was, Dr. Han wanted to go beyond these 142 species. To go further, the team built a database of evolutionary traits shared by species with the most vulnerable ACE2 receptors. This is a technique that has been used successfully in the past on rodents and bats, to assess their likelihood of acting as reservoirs of viruses, including Ebola and Zika. It is based on the idea that particular proteins from species with similar physiologies and lifestyles could evolve in similar ways.
The researchers studied everything they could – from the extent of diet, metabolic rate and age of sexual maturity to litter size, lifespan, geographic distribution, and phylogenetic relationships. – on more than 5,000 mammals for which little or no information on ACE2 receptors was available. With that huge database completed, they fed the results into a machine learning system that had been trained on the characteristics of the 142 species they had already examined. The result was the revelation of 540 species that appeared likely to have vulnerable ACE2 receptors and therefore the potential to function as covid reservoirs.
Most of the primates were on this list, which, given that people are also primates, was expected. Given the suspicions about the origins of SARS-CoV-2, the inclusion of 35 types of bats also came as no surprise. Surprises, however, there were. While the common house mouse does not appear to be a risk, which is good news, two of its rodent companions, the rice field rat and the Malaysian field rat, both do. Since these species are often preyed upon by domestic cats, themselves now known to be susceptible to viruses, this provides a route through which people could become infected.
Dozens of other species have also been reported as potential reservoirs. These included red foxes and raccoon dogs – two creatures that, like mink, are sometimes bred for their fur – and white-lipped peccaries (pig-like creatures found in South and Central America) and nilgai ( a large Asian antelope), which are occasionally raised, but also hunted and eaten.
Of the most common farm animals, the species of most concern is the water buffalo. It is estimated that there are more than 200m in the world, acting both as beasts of burden and sources of milk. And other frequently hunted animals, such as duiker (another antelope), warty pig and mule deer were also found to be vulnerable, along with some rarities, including two critically endangered antelopes, the addax and the scimitar-horned oryx (photo below), which was once extinct in the wild and is only now being reintroduced. In these cases, the threat weighs less on humans than on the survival of the species.
Pay the bison bill
The vast array of species involved amazes Dr. Han. “I never imagined that we would one day see a virus with such a high potential for interspecies infection,” she says. “It appears that there are at least an order of magnitude more species susceptible to infection with SARS-CoV-2 than any other zoonotic virus I can think of.”
Warned, however, is warned. And here there may be a lesson in keeping Arsenal weapons sharp. One of the reasons Dr. Han’s study took so long from start to publication is the disparate nature of the sources it had to draw on. Scattered as they were in the natural history collections of the world, their assembly took time. Many museums are now working to make their collections accessible electronically. To some, this may seem like a low priority. Work like this suggests not.