The search for animals that could carry the next deadly virus

Which animal is most likely to host the next deadly coronavirus?

With the Covid-19 pandemic fueling a sense of urgency, researchers are finding new ways to predict the answer to that question.

“We are thinking about the next one,” says Maya Wardeh of the University of Liverpool, one of the authors of an article in the journal Nature Communications who found that there are many more mammals that can be infected with multiple coronaviruses than was previously known.

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Several countries around the world are involved in or funding programs to test wild animals that have been linked to previous outbreaks or are considered to be at high risk, such as bats and rodents. Samples are collected and sequenced to identify new viruses, including those with the potential to infect humans. Efforts are also underway, including one at Ohio State University, to test domestic, wild, zoo and livestock animals to see if they can catch SARS-CoV-2, the pathogen that causes Covid-19 infections.

The Covid-19 pandemic spawned additional strategies to better quantify risks, make more accurate predictions, and then identify which animals need closer surveillance.

“You can’t look for something dangerous everywhere all the time. This is not sustainable and is expensive and hard work, especially if you don’t know what you are looking for, ”says Barbara A. Han, a disease ecologist at the Cary Institute of Ecosystem Studies in Millbrook, NY, who is applying the existing prediction algorithms for new combinations of ecological and other data to better predict the risk of SARS-CoV-2 disease in animals. Her and her colleagues ‘research combines data on the animals’ ACE2 receptors, which the virus uses to infect human cells, with information on the habitats, diets, metabolism and biology of animals, to predict which specific animals and species may be infected with SARS-CoV-2 and pass it on to others.

“We wanted to make more accurate predictions that could be tested in the field,” said Dr. Han.

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Making the leap

Most human infectious diseases come from animals and then “spill over” to humans. Viral outbreaks such as Ebola virus disease, Middle East respiratory syndrome and severe acute respiratory syndrome have been linked to human interactions with algae, dromedary camels, non-human primates and rodents. Many scientists believe that SARS-CoV-2 probably originated in animals, but it is still a matter of debate.

Scientists are concerned not only with animals that may have caused the initial overflow to humans, but also with the potential for humans to transmit the coronavirus to animals. In such cases, the disease can remain in the animal population, continuing to infect animals and potentially infect humans again. There are already reported cases involving mink in the US and Europe that initially caught Covid-19 in humans and then transmitted the virus back to people. Viruses often make genetic changes as they spread between hosts. If the animals eventually transmit a more lethal variant of the virus back to people, it could undermine efforts to control the pandemic through vaccination, says Dr. Han.

According to the Centers for Disease Control and Prevention, a small number of pet dogs and cats have been reported to be infected with SARS-CoV-2 worldwide, including in the United States. Studies are underway to examine which animals can transmit the disease to humans. The data so far show that dogs can be infected, but they don’t seem to spread the virus to other animals of the same species as easily as cats or ferrets, at least in the laboratory.

Vanessa Hale of Ohio State University, which launched eScout, a surveillance program for Covid-19, is testing SARS-CoV-2 on animals and the environment. Surveillance teams target cats in animal shelters and veterinary practices, pigs at farm fairs and animals captured by hunters and hunters, among others. So far in Ohio, all animals tested since May 2020, including ferrets, horses and goats, are negative. “We don’t want people to be afraid of cats and dogs in their homes,” says Hale. “At this point, animals are not playing a significant role in human infections.”

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A difficult process

For some scientists, the most urgent threat to public health is the potential for SARS-CoV-2 to recombine with another coronavirus in an animal, a process that can occur when two viruses infect the same animal, viruses exchange genetic material and, in they then create a new disease, says Dr. Marcus Blagrove, from the University of Liverpool, one of the authors of the Nature Communications article who tried to predict where new coronaviruses might arise.

The new study identified more mammals than currently known that could be potential sources for the generation of new coronaviruses. Some involve familiar names believed to be sources or intermediaries in previous coronavirus outbreaks, such as horseshoe bats, civets, dromedary camels and pangolins. But there were also new suspects that emerged through the team’s analysis, including the African green monkey and the Asian yellow bat. Other animals on the watch list include the common hedgehog, the European rabbit and domestic cats, the study concluded.

Predicting future outbreaks is not easy. On the one hand, pandemics tend to happen more often, say the researchers, driven by human behavior that is difficult to change. Farms and markets contain domestic and wild animals that live nearby and increase the potential for diseases that spread between animals and people. People continue to invade wildlife habitats through deforestation and the construction of roads and cities.

“We are putting ourselves in greater contact with animals and their microbes,” says Dr. Scott L. Nuismer, professor in the biological sciences department at the University of Idaho.

“There are so many different ways that a virus can spread to people, and it’s hard to take them all into account,” says Simon Anthony, a virologist at the University of California, Davis.

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Dr. Anthony says that developing mathematical and statistical ways to discern patterns and make better predictions is helpful. But the overflow process is complex, not fully understood and probably involves random events that, by definition, cannot be predicted. “We need all the help we can get to make decisions. But many chances occur in virus outbreaks, ”he says.

When trying to create a better algorithm to predict the animals that are likely to host SARS-CoV-2, researchers often encounter challenges. Databases contain much more information about animals that people have been studying for decades because of longstanding research by scientists or because animals are an important industry, such as poultry.

For example, bats are known as important sources of coronavirus, but data sets containing genetic sequences for these viruses are not comprehensive, especially compared to avian flu databases, says Maciej Boni, an evolutionary biologist and associate professor at the University State of Pennsylvania. Before Covid-19, there was no economic incentive for bat studies, he says, while the poultry industry is a multi-billion dollar business. In addition, many bats prefer to gather in dark, remote locations that are not always easy to reach. “Populations of bats die and no one knows about it,” says Dr. Boni. “Bats are much more difficult to taste than chickens.”

Dr. Han, of the Cary Institute, says that, in building their prediction algorithm, the research team looked for genetic sequence data from ACE2 receptors in animals. But no single database contained all the information that scientists need to know. In the case of Dr. Han’s study, the genetic sequence data on some animals’ ACE2 receptors was incomplete, with information from just 142 mammals out of about 6,000. Some of the most robust data involved fish with ray fins, which were not considered essential to predict future coronavirus pandemics, given what is known about the transmission of SARS-CoV-2.

Thus, they also collected information from other databases on animal habitats, diets, metabolism and biology, which they then combined with sequence and molecular data to provide information on which animals have the ability to become infected with SARS-CoV-2 and pass it on to others.

Some animals have been shown to be highly likely to transmit SARS-CoV-2, but unlikely to encounter humans regularly – such as the scimitar horned oryx or addax, says Dr. Han. These animals have been down on the list of animals that need closer surveillance. At the top of the list were deer mice and white-footed mice, which usually harbor pathogens and thrive living among humans. It turns out that when it comes to making predictions about the animals most likely to be involved in future pandemics, Dr. Han says, “contact with humans is the most important element.”