Did Omicron Come From Mice? Animals Infecting Humans Is Happening

Many species are susceptible to Covid, including those present in US cities and suburbs like deer and mice. 

New research suggests that the Omicron variant jumped from humans to mice, then back to humans again, where it spread like fast and widely. JL 

Carolyn Kormann reports in The New Yorker:

Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans. Pet dogs and cats, then tigers and lions at the Bronx Zoo. Infected zoo animals include gorillas, cougars, otters, spotted hyenas, and hippos. Species shown to be susceptible to sars-CoV-2 include cows, African green monkeys, macaques, baboons, golden hamsters, dwarf hamsters, ferrets, raccoon dogs, European rabbits, deer mice, bank voles, skunks, marmosets, and tree shrews, wild white-tailed deer and snow leopards.

Last Thanksgiving, Rilu, an eleven-year-old snow leopard and father of seven, began sneezing and wheezing. Snow leopards are native to the Himalayas, but Rilu was born in a zoo in Oklahoma City, then moved to the Miller Park Zoo, in Illinois, in 2011, to form part of the Species Survival Plan—the zoos’ matchmaking effort to maintain a genetically diverse “insurance” population of endangered animals. A PCR test in early December confirmed that Rilu had covid-19. He developed pneumonia and grew weaker, despite various attempts at treatment. On January 6th, he became the fifth captive snow leopard in the United States to die from covid-19 complications within three months. There are roughly five thousand snow leopards in the wild, according to conservationists’ best estimates. Five leopards is, on a species level, equivalent to 7.9 million humans—or, nearly every person in New York City. (More than 5.7 million humans have died from covid-19 globally, over two years.) The leopard deaths are, perhaps, the pandemic’s most tragic example of reverse zoonoses—when humans transmit a pathogen back to animals.

Because ancestral sars-CoV-2 initially evolved in bats, then somehow found its way into humans, it is called a “zoonosis”—a disease that transmits from animals to us. Roughly seventy-five per cent of all emerging infectious diseases are zoonoses. But, as scientists learned in the early months of the pandemic, sars-CoV-2 transmits easily back to other species. It isn’t a picky virus, either. “I can’t think of any single zoonotic virus with an equivalently broad host range,” Barbara Han, a disease ecologist, told me.

First, there were pet dogs and cats, then tigers and lions at the Bronx Zoo. The list of infected zoo animals now includes gorillas, cougars, otters, spotted hyenas, and hippos. Dozens of other species were shown to be susceptible to sars-CoV-2 in experimental infections in a lab, including cows, African green monkeys, macaques, baboons, golden hamsters, dwarf hamsters, ferrets, raccoon dogs, European rabbits, deer mice, bank voles, skunks, marmosets, and tree shrews. Outside of zoos, investigators found that wild populations of free-ranging white-tailed deer across North America had been infected with sars-CoV-2.

Most recently, on February 7th, scientists at Penn State posted a paper (not yet peer-reviewed), revealing that the Omicron variant was widespread among white-tailed deer on Staten Island. (The blood and nasal samples came from a sterilization program under way to control the borough’s deer population.) It’s unclear whether infected deer display symptoms, but they seem to shed and spread the virus in the same way that humans do. Evidence from antibody analysis suggests they might even be susceptible to reinfection, which would indicate the species’ potential as a sars-CoV-2 reservoir—a distressing thought, considering that their population numbers roughly thirty million and they thrive among humans. But whether the first deer to be infected picked it up from a person or another animal “remains an open question,” Suresh Kuchipudi, a virology professor at Penn State and the lead scientist on the study, told me. “The sort of hidden exposure of the virus in animals is the most alarming part of this whole process.”

When sars-CoV-2 spills over into new animal hosts, it adapts, accumulating mutations that could give rise to a new variant, which could then spill back over into people. “We were hoping to end this pandemic by, you know, vaccinating everybody,” Kuchipudi told me. “But, when the virus finds safe haven in another animal, or animals, and continues to circulate, that creates a much more complex ecological-transmission network, which is much more difficult to comprehend and manage.”

Reverse zoonosis might explain where Omicron came from. After it emerged in November, in South Africa, the scientists who sequenced its genome quickly saw something strange. Omicron has nearly fifty mutations when compared with the original 2019 virus, and thirty-seven of them are clustered on its spike protein; this is far more than there were on any of the four other variants of concern (Alpha, Beta, Gamma, and Delta). On the sars-CoV-2 family tree—a map formed by about eight million publicly shared sars-CoV-2 genomes—Omicron sits out on a limb, at the end of an exceptionally long branch. Scientists concluded that it did not derive from any of the other variants, but, rather, it seemed to have evolved along its own trajectory. But where had it been hiding out?

 

In December, Wenfeng Qian, a Beijing-based scientist, and a group of his colleagues, offered a possible answer: mice. In a paper published in the Journal of Genetics and Genomics, they argued that Omicron’s mutations had been subjected to greater pressure to evolve than the other sars-CoV-2 variants, which had evolved in human hosts—indicating, perhaps, that it had evolved in a different species. They also found that some of the mutations in Omicron’s spike are the same mutations that had already been found to help sars-CoV-2 infect mice. (Scientists identified these mutations when they created mouse-adapted strains of sars-CoV-2 in order to research vaccines and therapeutics.) “Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans,” Qian and his co-authors wrote. How infected mice might have infected people is anyone’s guess.

Trevor Bedford, a professor at Fred Hutchinson Cancer Research Center in Seattle, and a leading expert on viral evolution and surveillance, said that Qian’s paper “is the most compelling case for rodent origin I’ve seen.” But Bedford favors a more popular hypothesis—that Omicron evolved in a chronically infected, immunocompromised patient, such as someone who is H.I.V.-positive. “I’d place more likelihood on the chronic infection route,” he wrote in an e-mail, “but definitely not certain of this origin.” Richard Lessells, an infectious-disease physician in South Africa who was part of the team that initially identified Omicron, agreed. “My own view is still that chronic infection and evolution in a human host may be the most likely mechanism.”

Omicron has a mysterious insertion in its genome, which, Bedford believes, could have been acquired when it was replicating for months in an immunocompromised person’s cells. But Qian said that this “fragment in Omicron consists of just nine nucleotides, making it too short to reveal its source.” He and his co-authors argue that the more parsimonious explanation is that it came from another location within the sars-CoV-2 genome itself. “Every sars-CoV-2 genome has this fragment,” he wrote in an e-mail. (A new group formed by the World Health Organization to research the origins of the pandemic—the Scientific Advisory Group for the Origins of Novel Pathogens, or sago—is currently completing a report that will address the emergence of Omicron. Its findings, however, which are largely based on available data, are not expected to settle the debate.)

Omicron most likely evolved to its current form in South Africa, where it was first detected, or somewhere in the wider region, where both vaccination rates and disease surveillance are low, until it began rapidly infecting people in South Africa. And yet, its geographic origin remains unclear, Marietjie Venter, a South African researcher and the chair of sago, told me. Maybe “it was just detected here first because we had almost no sars-CoV-2 by the end of October, and it could outcompete the Delta variant through partial immune evasion.” She added that they later found that the variant was already circulating in Europe by the time her group detected it. In any case, “at the moment,” Venter said, “the hypothesis of reverse transmission to a mouse is interesting, but at this stage theoretical.” It’s based only on analysis of mouse strains in labs, not on the detection of Omicron in wild mice.

This could be because disease surveillance in wild animals is challenging, if it happens at all. House and deer mice have been found, in the lab, to be not only susceptible to sars-CoV-2, but capable of transmitting the virus through aerosolized particles (from cage to cage). Scientists have posited that animals could contract the virus in human wastewater, which, research has revealed, is teeming with sars-CoV-2 variants. The wide-ranging white-footed mouse, well known among New Yorkers, and very closely related to the deer mouse, was predicted to be susceptible by a computer model that Barbara Han and her colleagues built. “It coexists quite easily with us,” she said, and presents a risk of “carrying sars-CoV-2, becoming infected, and transmitting onward.” But whether a mouse could transmit a sars-CoV-2 variant to humans is unknown. “Airtight evidence of that nature is typically very difficult to come by,” Han said.

Until recently, there had been only one known secondary spillover event—when sars-CoV-2 was found to have infected mink and spread like wildfire on fur farms across Europe; later, in the Netherlands, the virus was transmitted from mink back to farmers. Thousands of mink were culled, farms were shuttered, and the fur industry was destroyed. Last week, however, researchers found that pet hamsters had likely carried the Delta variant into Hong Kong, sparking an outbreak in a pet store that eventually led to infections in dozens of people.

Because Hong Kong has a robust contact-tracing program, which is part of a wider effort to keep case counts at zero, officials could easily determine that the outbreak began in the pet store; this would be almost impossible in the United States and most other places. With wildlife—unmonitored, mostly unseen—anything is possible. “Given how many people are infected in the world,” Han said, “the chances of sars-CoV-2 becoming established in a new animal reservoir and just becoming this endemic source of new sars-CoV-2 virus seem to be quite high.”