Some experts believe the Omicron variant may have evolved in a host animal
WWhen variants of Covid-19 emerge, the accepted wisdom is that the constellation of mutations they contain developed in an immunocompromised person who contracted the virus and was unable to shake off the infection. But some scientists have an alternate theory as to where the latest worrying variant, Omicron, may have acquired the unusual mutations that dot its spike protein.
They speculate that the virus may have evolved into another animal species.
The theory is that a certain type of animal, potentially rodents, was infected with the SARS-CoV-2 virus in mid-2020. In this new species, the virus evolved, accumulating around 50 mutations on the spike protein before spreading again to humans.
Kristian Andersen, an immunologist at the Scripps Research Institute, is among those who have raised the idea that Omicron may have emerged from a reverse zoonotic event.
(A zoonotic event occurs when an animal pathogen begins to infect and spread among humans. A reverse zoonosis occurs when such a virus returns to an animal species.)
“I know that most people think that these [come from] immunocompromised individuals, and I think it’s plausible, but to be completely honest I actually think this reverse zoonosis followed by a new zoonosis seems more likely to me given the available evidence from the really deep branch, then the mutations themselves, because some of them are quite unusual, âAndersen told STAT.
“I don’t think we should rule that out, because I think it’s definitely on the table.”
A number of other scientists who study the evolution of viruses told STAT they believe the idea is not out of the question. Some give more weight to the theory that variants develop in immunocompromised people, while others believe that there is not enough evidence at this point to favor one option over the other.
“Personally, I think it’s probably more likely that it was circulating undetected, in an immunocompromised individual,” Emma Hodcroft, molecular epidemiologist at the Institute of Social and Preventive Medicine in Bern, said by email in Swiss. That said, Hodcroft insisted that it is important to explore the hypothesis.
“I would certainly view this as a plausible alternative hypothesis to evolution during persistent infection in a human,” said Andrew Rambaut, professor of molecular evolution at the Institute of Evolutionary Biology in Edinburgh. He warned that finding a definitive answer will not be quick.
“I’m not sure we’ll be able to say that for sure for a while,” Rambaut wrote in an email.
One of the special features of SARS-2 underlies this thinking. This is what virologists describe as a promiscuous virus; it is capable of infecting a number of species. Domestic dogs and cats. Big cats. Mink. Virginia deer. Given the ease with which the virus appears to pass from species to species, people studying it assume this list will grow.
The original virus that emerged from Wuhan, China in early 2020 has not infected rodents. But as variants – Alpha, Beta, Delta – began to emerge, these viruses could infect rodents.
Robert Garry, professor of microbiology and immunology at Tulane Medical School, has been tracking the SARS-2 mutations that have emerged. Seven are associated with rodent adaptation – changes that appeared to allow the virus to infect mice, rats and related species. These seven mutations are all found in Omicron, Garry noted. He thinks it’s a fluke that the variant developed in an animal or human host, but if it’s the first, his bet would be on rodents.
Getting a firm answer can take a lot of luck. Scientists are examining various animal species to see if they can be infected with SARS-2; if they found viruses like Omicron in any of them, it would tip the needle.
But Michael Worobey, professor of evolutionary biology at the University of Arizona, believes that one could do experiments on selected species of wild animals to see if they can be infected and if, when infected, similar patterns of viral evolution occur.
Studying the molecular clock of viruses that spread in animals – looking at the speed at which they evolve and comparing it to the evolution of SARS-2 in humans – could also provide some clues, said Worobey, who initially thought Andersen’s idea was not impossible, but not the most likely explanation for Omicron. After hearing the details of the explosive white-tailed deer epidemic, he rethinks the idea.
For Worobey, the question is whether an animal species can become chronically infected with SARS-2 – in fact, if there are animal species in which SARS-2 persists as it does in immunocompromised people. This could exert positive selective pressure on the virus, in other words causing it to mutate to stay ahead of the animal’s immune response.
“It moves my thinking in terms of Omicron that can come from a reservoir, if there is [animal] reservoirs that cause chronic infections, âhe said.
Part of what makes Andersen question an animal source is the fact that the variant dates back to viruses that spread over a year ago. âThat in itself you have to be able to explain,â he said.
Angela Rasmussen, coronavirus virologist at the Vaccines and Infectious Diseases Organization at the University of Saskatchewan, agreed.
“I think it’s pretty obvious to everyoneâ¦ that this virus has been on an independent evolutionary path for quite some time and it’s very surprising, which to me is kind of like saying well, the idea that that might beâ¦ plausible. âshe said.
Whether or not this variant has appeared in another species, given SARS-2’s ability to skip species, it’s possible the world will be facing animal-derived variants in the future, Garry warned. The result of that? âWe’re going to have to keep fine-tuning the vaccines. “