As omicron cases crop up around the world, scientists are trying to determine the variant's origin. But some experts disagree on where—and how—this puzzling variant evolved.

The omicron variant: The 'good,' 'bad,' and 'ugly' scenarios

Did omicron originate in South Africa?

Omicron was first identified by South African scientists, who reported the variant to the World Health Organization (WHO)—however, it's not certain that the variant started in that country. For example, the National Institute for Public Health and the Environment in the Netherlands said retests of samples taken on Nov. 19 and 23 found that omicron was already in the Netherlands before South Africa reported it to WHO.

In addition, Nigeria's national public health institute on Wednesday announced it had detected the country's first omicron case in a sample that was collected in October. "Retrospective sequencing of the previously confirmed cases among travelers to Nigeria also identified the omicron variant among the sample collected in October 2021," said Ifedayo Adetifa, director-general of the Nigeria Centre for Disease Control. Nigeria was the first country to detect the omicron variant in West Africa since it was first reported in southern Africa.

As of Nov. 30, theEuropean Centre for Disease Prevention and Control confirmed 33 omicron cases across eight countries in Europe, including the Netherlands, Austria, Belgium, Czechia, Denmark, Germany, Italy, and Portugal. It's also been found in other areas of the world, from Hong Kong to Israel, NPR reports.

As a result, it's unclear where the variant actually emerged, STAT News reports—and South Africa and Botswana's may have spotted it early on only because of the strength of those area's genetic sequencing networks.  

Scientists analyze the variant's genetic code

As scientists race to learn more about omicron, they have turned to clues in the variant's genetic code to determine its origin.

According to Trevor Bedford, a computational virologist and professor at the Fred Hutchinson Cancer Research Center, "It's been very common to use an evolutionary tree—or a family tree—of these SARS-CoV-2 viruses to catch introductions in places like Australia and Taiwan that have not had a lot of local spread."

"You can figure out where the importations are coming from by looking at the viral genome and checking, 'Is it close in its sequence characteristics to [strains] that are circulating elsewhere that have been sequenced and shared with the database?'" Bedford added. 

As scientists collect samples throughout a region, they can track how a particular strain picks up additional—often benign—mutations until it turns into a significantly different strain, NPR reports.

"With omicron, your closest sequences are back from mid-2020—so over a year ago. That is very rare to see," Bedford said.

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Although scientists were able to determine that omicron evolved from a strain that was circulating in mid-2020, they were not able to trace any intermediate versions they expected to find as omicron morphed into its current form, NPR reports. In fact, Bedford said, "[Omicron] doesn't tie into anything that was circulating more recently," even though its it has mutated significantly from the 2020 strain.

3 possible originations

So where could omicron have come from? Scientists have three possible hypotheses:

1. An animal source

According to Bedford, one possibility is that the mid-2020 strain infected an unknown animal population, mutated as it spread among them, and recently began infecting humans again.

Kristian Andersen, an immunologist at the Scripps Research Institute, said, "[I] actually think this reverse zoonosis followed by new zoonosis seems more likely to me … I don't think we should dismiss that possibility, because I think it's definitely on the table."

However, Bedford doesn't believe this is the most likely cause. "This is getting technical," he said, but you typically see signs of an animal's genetic material in the virus' genome—but instead there's an insertion of human RNA "that suggests that along [omicron's evolutionary] branch, it was evolving in a human."

Separately, Aris Katzourakis, an evolutionary biologist at the University of Oxford, said he is also skeptical of the variant's evolution in an animal due to the number of human infections. "I'd start worrying about animal reservoirs more if we were succeeding in suppressing the virus, and then I could see it as somewhere it might hide," he said.

2. A 'cryptic spread' in an unmonitored region

Another possible scenario is that the mid-2020 strain began circulating somewhere that has minimal monitoring and would allow the virus to evolve undetected—"perhaps somewhere in Southern Africa," Bedford suggested. "And eventually, by the time you get to 2021, it's picked up enough mutations that it has become [much more] transmissible and then kind of explodes onto the scene at that point," he added.

However, Bedford said that he finds the idea of "cryptic spread" difficult to believe. "Because it would seem that as [this strain of the virus] was on its path to becoming omicron and becoming a quite transmissible virus, [the earlier versions] would have started to spread more widely before just now, " he said.

Richard Lessells, an infectious disease specialist at the University of KwaZulu-Natal and a member of the team that identified omicron in South Africa, echoed Bedford's skepticism. "If you've got representative sequencing and frequent sequencing, and if you can be nimble enough to respond to what you're observing in the cases in the diagnostic lab, then you can pick up these variants that are at a relatively early stage," he said. "So you'd have to have a pretty big blind spot to be missing something that's really evolving over a period of months."

3. Incubation in an immunocompromised person

The virus may also have incubated and evolved inside of a single person—likely evading detection by health officials. More specifically, scientists have theorized that the virus could have mutated inside of an individual with a suppressed immune system—for example, an individual with an untreated HIV infection.

According to Bedford, an immunocompromised person's immune system may be strong enough to keep them from dying as a result of a coronavirus infection. However, it probably wouldn't be strong enough to completely clear the virus. As a result, the virus could stay inside the person for several months—and continually reproduce. With each replication, there is a chance the virus could acquire a mutation that increases its ability to evade the person's antibody-producing immune cells, NPR reports.

"It creates this kind of cat-and-mouse game where the immune response is chasing and the virus is running," said Bedford. "And so over the course of the year, if you look in these individuals, you see, at the end of that time, generally a quite evolved virus." (Aizenman, "Goats and Soda," NPR, 12/1; Kupferschmidt, Science, 12/1; Branswell, STAT News, 12/2; Chappell, NPR, 11/30; AP/NPR, 12/1; Joseph, STAT News, 11/26)