Omicron's 'wacko' combination of mutations has scientists split over whether it developed in humans or animals

• The Omicron variant has a strange set of mutations. It doesn't resemble Delta, the dominant strain.
• That has led scientists to wonder about its origin — namely, whether it came from humans or animals.
• One of the most promising theories suggests Omicron emerged in an immunocompromised person.

Omicron looks odd, even to scientists who study coronavirus strains.

The variant has spread to nearly 30 countries since it was first detected in Botswana roughly three weeks ago. Scientists are trying to make sense of its concerning number of mutations, which could make Omicron more transmissible then Delta, render vaccines less effective, or lead to more severe disease. For now, those answers are pending. 

Omicron doesn't resemble common coronavirus variants like Alpha or Delta (still the world's dominant strain), and many of its strange mutations haven't been spotted in other variants before. Scientists estimate that Omicron's closest ancestors date back to mid-2020. 

"It's not the son or daughter of Delta," Andrew Read, who studies the evolution of infectious diseases at Pennsylvania State University, told Insider. "It branched off earlier from the human lineages, so it has been somewhere for awhile. So where's that reservoir? Was it an individual person or an individual animal or a population of animals or population of people that haven't been properly sampled?"

Scientists are debating the answer.

One of the most promising theories is that Omicron emerged in an immunocompromised host, such as a person with an untreated HIV infection. People with weakened immune systems are common reservoirs for mutations, since their bodies often struggle to clear viruses, allowing the pathogen to replicate for months.

The theory may explain why Omicron contains "such a wacko combination of mutations," Charity Dean, a former official at the California Department of Public Health, told Insider. 

"It's probably more likely that this was the result of ongoing molecular evolution inside a single host that spilled over into the population," she said.

But some scientists aren't ready to rule out the idea that Omicron developed in an animal species. Robert Garry, a professor of microbiology and immunology at Tulane Medical School, noted to STAT News this week that Omicron carries several key mutations that could have helped the coronavirus infect rodents. 

"It could be that the virus moved into a wild animal population and then we didn't see it for a while and it came back — that's not a crazy hypothesis," Martin Hibberd, professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine, told Insider. "But we don't have as much evidence of that."

Other coronavirus variants likely evolved in immunocompromised people

Omicron contains 50 mutations in total, more than two dozen of which are brand new. To develop that many mutations, scientists say, the virus needs plenty of opportunities to replicate — a sign that Omicron likely evolved in an immunocompromised host.

"We don't know at the moment to any great detail how long infections can persist in individual animals of any sort, whereas we do know that immunocompromised humans can have chronic infections," Read said. 

A 2020 case study published in the New England Journal of Medicine found that the coronavirus persisted for five months in a 45-year-old man with antiphospholipid syndrome, an immune disorder. During that time, it developed key mutations found in other variants of concern like Delta, Alpha, and Gamma.

Researchers also suspect that the Alpha variant developed in an immunocompromised person.

Omicron "reminds me a little bit of how the Alpha variant arose in the UK," Hibberd said. "That's why people have thought about this as perhaps originating in a single patient."

The animal theory could explain the variant's early origin

Still, scientists say it's theoretically possible for the coronavirus to chronically infect animals. Outbreaks in white-tailed deer last winter and Dutch mink farms in June 2020 may be evidence of that — though Hibberd and others remain skeptical.

"I don't see why the virus would have an easier time in an animal than in a human," Hibberd said. "We did see that in Europe a little bit with the mink infection and we were worried about those variants that got passed through the mink outbreak, but in the end they didn't prove to be any more advantageous than the current strains."

The animal theory, however, may help explain why scientists detected the first Omicron case on November 9, when the variant's lineage dates back to last year. Had Omicron been lurking in animals, it would have been particularly difficult to spot.

"The surveillance in humans has only recently ramped up to something that we're not embarrassed about," Read said. "The surveillance in animals is an awful long way away."

It's probably too late to find 'patient zero'

Scientists may never know Omicron's origin.

"If we actually found the Omicron variant in a wildlife population, that would obviously be a smoking gun," Read said. But, he added that the variant's continued spread increases the odds that it will spill over to animal species eventually, if it hasn't already. That means there's a narrow window to see if animals were indeed the original hosts.

Hibberd expressed reservation about scientists doing too much sampling for the variant in wild animals, since our interactions with them increase the odds of new pathogens emerging. 

"I don't want people going around chasing bats, for example, because we might cause more trouble than where we're trying to fix," he said. 

Even finding an original human host for the variant would be difficult.

"If we found an immunocompromised human with Omicron now, we wouldn't know whether that was patient zero," Read said.  

So scientists are left to wager their best guesses amid a dearth of information.

"My money's on the immunocompromised person, but not a lot of money," Read said.