Virus World

Humans are not the only species facing a potential threat from SARS-CoV-2, the novel coronavirus that causes COVID-19, according to a new study from the University of California, Davis. An international team of scientists used genomic analysis to compare the main cellular receptor for the virus in humans -- angiotensin converting enzyme-2, or ACE2 -- in 410 different species of vertebrates, including birds, fish, amphibians, reptiles and mammals.  ACE2 is normally found on many different types of cells and tissues, including epithelial cells in the nose, mouth and lungs. In humans, 25 amino acids of the ACE2 protein are important for the virus to bind and gain entry into cells. 

The researchers used these 25 amino acid sequences of the ACE2 protein, and modeling of its predicted protein structure together with the SARS-CoV-2 spike protein, to evaluate how many of these amino acids are found in the ACE2 protein of the different species. "Animals with all 25 amino acid residues matching the human protein are predicted to be at the highest risk for contracting SARS-CoV-2 via ACE2," said Joana Damas, first author for the paper and a postdoctoral research associate at UC Davis. "The risk is predicted to decrease the more the species' ACE2 binding residues differ from humans." About 40 percent of the species potentially susceptible to SARS-CoV-2 are classified as "threatened" by the International Union for Conservation of Nature and may be especially vulnerable to human-to-animal transmission. The study was published Aug. 21 in the Proceedings of the National Academy of Sciences. 

"The data provide an important starting point for identifying vulnerable and threatened animal populations at risk of SARS-CoV-2 infection," said Harris Lewin, lead author for the study and a distinguished professor of evolution and ecology at UC Davis. "We hope it inspires practices that protect both animal and human health during the pandemic."

Endangered species predicted to be at risk

Several critically endangered primate species, such as the Western lowland gorilla, Sumatran orangutan and Northern white-cheeked gibbon, are predicted to be at very high risk of infection by SARS-CoV-2 via their ACE2 receptor. Other animals flagged as high risk include marine mammals such as gray whales and bottlenose dolphins, as well as Chinese hamsters. Domestic animals such as cats, cattle and sheep were found to have a medium risk, and dogs, horses and pigs were found to have low risk for ACE2 binding. How this relates to infection and disease risk needs to be determined by future studies, but for those species that have known infectivity data, the correlation is high. In documented cases of SARS-COV-2 infection in mink, cats, dogs, hamsters, lions and tigers, the virus may be using ACE2 receptors or they may use receptors other than ACE2 to gain access to host cells. Lower propensity for binding could translate to lower propensity for infection, or lower ability for the infection to spread in an animal or between animals once established. Because of the potential for animals to contract the novel coronavirus from humans, and vice versa, institutions including the National Zoo and the San Diego Zoo, which both contributed genomic material to the study, have strengthened programs to protect both animals and humans. "Zoonotic diseases and how to prevent human to animal transmission is not a new challenge to zoos and animal care professionals," said co-author Klaus-Peter Koepfli, senior research scientist at Smithsonian-Mason School of Conservation and former conservation biologist with the Smithsonian Conservation Biology Institute's Center for Species Survival and Center for Conservation Genomics. "This new information allows us to focus our efforts and plan accordingly to keep animals and humans safe." 

The authors urge caution against overinterpreting the predicted animal risks based on the computational results, noting the actual risks can only be confirmed with additional experimental data. The list of animals can be found here. Research has shown that the immediate ancestor of SARS-CoV-2 likely originated in a species of bat. Bats were found to be at very low risk of contracting the novel coronavirus via their ACE2 receptor, which is consistent with actual experimental data.  Whether bats directly transmitted the novel coronavirus directly to humans, or whether it went through an intermediate host, is not yet known, but the study supports the idea that one or more intermediate hosts was involved. The data allow researchers to zero in on which species might have served as an intermediate host in the wild, assisting efforts to control a future outbreak of SARS-CoV-2 infection in human and animal populations.

No matter what happens now, the virus will continue to circulate around the world.  The coronavirus that causes COVID-19 has sickened more than 16.5 million people across six continents. It is raging in countries that never contained the virus. It is resurgingin manyof the ones that did. If there was ever a time when this coronavirus could be contained, it has probably passed. One outcome is now looking almost certain: This virus is never going away.  The coronavirus is simply too widespread and too transmissible. The most likely scenario, experts say, is that the pandemic ends at some point—because enough people have been either infected or vaccinated—but the virus continues to circulate in lower levels around the globe. Cases will wax and wane over time. Outbreaks will pop up here and there. Even when a much-anticipated vaccine arrives, it is likely to only suppress but never completely eradicate the virus. (For context, consider that vaccines exist for more than a dozen human viruses but only one, smallpox, has ever been eradicated from the planet, and that took 15 years of immense global coordination.) We will probably be living with this virus for the rest of our lives. Back in the winter, public-health officials were more hopeful about SARS-CoV-2, the coronavirus that causes COVID-19. SARS, a closely related coronavirus, emerged in late 2002 and infected more than 8,000 people but was snuffed out through intense isolation, contact tracing, and quarantine. The virus was gone from humans by 2004. SARS and SARS-CoV-2 differ in a crucial way, though: The new virus spreads more easily—and in many cases asymptomatically. The strategies that succeeded with SARS are less effective when some of the people who transmit COVID-19 don’t even know they are infected. “It’s very unlikely we’re going to be able to declare the kind of victory we did over SARS,” says Stephen Morse, an epidemiologist at Columbia University.

If not, then what does the future of COVID-19 look like? That will depend, says Yonatan Grad, on the strength and duration of immunity against the virus. Grad, an infectious-disease researcher at Harvard, and his colleagues have modeled a few possible trajectories. If immunity lasts only a few months, there could be a big pandemic followed by smaller outbreaks every year. If immunity lasts closer to two years, COVID-19 could peak every other year.  At this point, how long immunity to COVID-19 will last is unclear; the virus simply hasn’t been infecting humans long enough for us to know. But related coronaviruses are reasonable points of comparison: In SARS, antibodies—which are one component of immunity—wane after two years. Antibodies to a handful of other coronaviruses that cause common colds fade in just a year. “The faster protection goes away, the more difficult for any project to try to move toward eradication,” Grad told me. This has implications for a vaccine, too. Rather than a onetime deal, a COVID-19 vaccine, when it arrives, could require booster shots to maintain immunity over time. You might get it every year or every other year, much like a flu shot. Even if the virus were somehow eliminated from the human population, it could keep circulating in animals—and spread to humans again. SARS-CoV-2 likely originated as a bat virus, with a still-unidentified animal perhaps serving as an intermediate host, which could continue to be a reservoir for the virus. (SARS also originated in bats, with catlike palm civets serving as an intermediate host—which led officials to order the culling of thousands of civets.) Timothy Sheahan, a virologist at the University of North Carolina at Chapel Hill, wonders if, with SARS-CoV-2 so widespread across the globe, humans might be infecting new species and creating new animal reservoirs. “How do you begin to know the extent of virus spread outside of the human population and in wild and domestic animals?” he says. So far, tigers at the Bronx Zoo and minks on Dutch farms seem to have caught COVID-19 from humans and, in the case of the minks, passed the virus back to humans who work on the farm...