Science reports:

Since South African scientists announced last week they had identified an unsettling new variant of SARS-CoV-2, the world has anxiously awaited clues about how it might change the trajectory of the pandemic. But as big a mystery—if less urgent—is where and how Omicron evolved, and what lessons its emergence holds for avoiding future dangerous variants.

Omicron clearly did not develop out of one of the earlier variants of concern, such as Alpha or Delta. Instead, it appears to have evolved in parallel—and in the dark. Omicron is so different from the millions of SARS-CoV-2 genomes that have been shared publicly that pinpointing its closest relative is difficult, says Emma Hodcroft, a virologist at the University of Bern. It likely diverged early from other strains, she says. “I would say it goes back to mid-2020.”

That raises the question of where Omicron’s predecessors lurked for more than a year. Scientists see essentially three possible explanations: The virus could have circulated and evolved in a population with little surveillance and sequencing. It could have gestated in a chronically infected COVID-19 patient. Or it might have evolved in a nonhuman species, from which it recently spilled back into people.

Christian Drosten, a virologist at Charité University Hospital in Berlin, favors the first possibility. “I assume this evolved not in South Africa, where a lot of sequencing is going on, but somewhere else in southern Africa during the winter wave,” he says. “There were a lot of infections going on for a long time and for this kind of virus to evolve you really need a huge evolutionary pressure.”

But Andrew Rambaut of the University of Edinburgh can’t see how the virus could have stayed hidden in a group of people for so long. “I’m not sure there’s really anywhere in the world that is isolated enough for this sort of virus to transmit for that length of time without it emerging in various places,” he says.

Instead, Rambaut and others propose the virus most likely developed in a chronically infected COVID-19 patient, likely someone whose immune response was impaired by another illness or a drug. When Alpha was first discovered in late 2020, that variant also appeared to have acquired numerous mutations all at once, leading researchers to postulate a chronic infection. The idea is bolstered by sequencing of SARS-CoV-2 samples from some chronically infected patients. [Continue reading…]