As scientists around the world frantically try to work out the properties of the Omicron variant, one of the most puzzling questions concerns how the new strain came into existence in the first place.

We know that the variant has around 30 mutations on its spike protein – the part targeted by vaccines. It’s spreading quickly in South Africa where it was first identified, and has now been detected in 24 countries.

Yet Omicron’s origin story remains a mystery. Scientists have traced the variant’s lineage back to a strain that was circulating in mid-2020. But there’s no sign of the intermediate iterations of the virus which eventually led to Omicron. 

Working out how Omicron evolved matters. It will give clues about the strain’s transmissibility and lethality. But it also has profound implications for how we think about new variants and the policy measures we use in response to them.

Smoking gun?

One plausible theory is that the mutations developed in someone who was immunocompromised, whose weakened immune system was strong enough to prevent the virus from killing the host, but not strong enough to get rid of it completely. So the virus lingered, mutating and replicating, before eventually infecting someone else and spreading. Researchers have observed this phenomenon before with other variants.

But Kristian G. Andersen, a professor in the Department of Immunology and Microbiology at the Scripps Research Institute in California, is sceptical about embracing the immunocompromised theory: “While that’s certainly possible, we don’t have any data showing that’s the case,” he writes. “Let’s keep all hypotheses open.”

Andersen favours the idea that the virus jumped from human to animal, mutated, then jumped back to humans again. This “reverse zoonosis” hypothesis is consistent with the fact that SARS-COV-2 is a “promiscuous virus”, capable of infecting a large number of species. “Several of the mutations in Omicron have been observed in animals, including rodents,” writes Andersen.

“It’s a very interesting idea”, says Lawrence Young, a virologist and Professor of Molecular Oncology at the University of Warwick. “One of the fascinating things about the variants we’ve seen is that they have tended to be more infectious to animals than the original Wuhan strain.

“Regarding Omicron’s origin, you could call it a smoking gun. But you have to think about the proximity of humans to animal reservoirs in these populations to see whether it is in fact likely.”

Planning for Omega

If Omicron turns out to have mutated in an animal host, we may need to rethink the logic behind virus control measures; animal-to-human distancing (rather than human-to-human) would become much more important.

“We don’t do enough in thinking about the interactions of animals with humans,” says Young. “Around the world there isn’t as much research that joins up infectious disease in animals and infectious disease in humans. One would help prevent the other.”

If Omicron originated in someone with a suppressed immune system, then our priorities shift once again. Tulio De Oliveira, the South African scientist who first detected Omicron, has warned that the roughly eight million sub-Saharan Africans with unrecognised or poorly treated HIV are the people mostly likely to spawn mutations.

As Richard Lessells, an infectious disease specialist and part of De Oliveira’s team, put it: “The intervention here is clear. We just need to strengthen our HIV response and get as many people as we possibly can onto effective treatment regimens.” It’s worth noting that pandemic restrictions have disrupted the distribution of antiviral HIV drugs across sub-Saharan Africa.

Whichever explanation proves correct, the idea that universal vaccine coverage will stave off new variants doesn’t hold water. Vaccines save lives, and coverage should be extended across the world on that basis. But as Covid becomes endemic, it will be impossible to monitor all isolated populations, those with weak immune systems will continue to become infected, and SARS-COV-2 will continue to jump between animals and humans.

New variants are inevitable – Omicron won’t be the last. Working out how it evolved will help in deciding whether we want our response to this latest variant scare to be the model going forward.