A second and a third American patient have been confirmed to be infected with the Omicron variant: an adult male in Minnesota who recently traveled to New York for an anime convention, and an adult female in Colorado who recently returned from southern Africa.

The second known case of Omicron was confirmed as of Thursday morning, as KRON4 reports, and the vaccinated patient in Minnesota says he began showing symptoms not long after attending the Anime NYC 2021 convention at the Javits Center in Manhattan from November 19 to 21. This case suggests that the variant had already crossed into the U.S. the week before the San Francisco patient, confirmed as of Wednesday, landed back in the country from a trip to South Africa during Thanksgiving Week.

It's also further proof that the San Francisco case was extraordinary in the speed with which it was confirmed. That patient was tested on Sunday, November 28, the test came back positive on Monday, and by Tuesday night a UCSF lab was fairly certain they had an Omicron case. The Minnesota patient began feeling ill on November 22, and sought testing on November 24, as NPR reports. That means it was a full eight days for that sample to get genetic sequencing and be confirmed as Omicron.

Experts have since explained that the Omicron variant presents a specific signature that acts as a flag on a PCR test, but it still requires hours of sequencing in a lab for a sample to be definitively confirmed as the variant.

In the coming hours, we are likely to hear about more Omicron cases popping up around the country, following this second Minnesota case, as more aggressive surveillance work occurs. Update: A third U.S. case was confirmed Thursday in a vaccinated Colorado woman, as the Denver Post reports. The woman's travel dates are not yet being reported, but NPR reports that she had been traveling in multiple countries in southern Africa and she tested positive for COVID one day after returning to the Denver area. Her test was flagged by the state health system due to her recent travel, and subsequently genetically sequenced.

"This news is concerning, but it is not a surprise," said Minnesota Gov. Tim Walz in a statement from the health department about the new case there. "We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster."

As of Wednesday, the new "variant of concern" had been found in 24 countries, and while scientists say its constellation of mutations make it look like it will be highly infectious and could evade vaccines to a point, its actual transmissibility and virulence has yet to be proven in data.

That wide array of mutations was surprising to researchers in part because it appeared out of nowhere, and we're now learning more about how this strain might have become so highly mutated without being detected as that process took place. As NPR explains, experts are working with three different theories, and one seems the likeliest.

Epidemiologists tracking the pandemic have been able to create a family tree of sorts for the variants that have already been observed, and they've been able to see where a mutated variant has picked up its original genetic code.

"With Omicron, your closest sequences are back from mid-2020 — so over a year ago. That is very rare to see," says Trevor Bedford, a computational virologist and professor at the Fred Hutchinson Cancer Research Center in Seattle, speaking to NPR. Bedford explains that with a circulating variant, you should be able to see marks of more recent strains, but Omicron arrived with its base code from well over a year ago, as if it had been hiding all that time.

"It doesn't tie into anything that was circulating more recently," says Bedford. "Yet its mutations put it a long way from that 2020 strain."

The theories go like this: Omicron could have been a strain that jumped back into an animal population and then crossed back into people, but Bedford dismisses this one saying the code shows it was evolving inside a human; the variant could, maybe have been quietly circulating all this time in a corner of Africa with little genetic surveillance of virus samples; or option c) it's been steadily mutating inside a single, immunocompromised person — likely someone with an untreated HIV infection, whose immune system was strong enough to keep COVID in check, but not strong enough to fully clear the virus. In that patient, Omicron could have been mutating and learning its way around immune responses for over a year, before jumping back into the wider population.

If the latter scenario were the true one, it would point to a more urgent need for HIV treatment in places where it is harder to get, showing how one lingering pandemic can serve to amplify another one.

But, Bedford tells NPR, we can't yet rule out the possibility that Omicron has been circulating undetected in a wider population — which would show us that it is not, in fact, very transmissible, or it would have made itself known much sooner.

Related: Swift Sequencing of Omicron Sample at UCSF Highlights Challenges of Tracking Variant's Spread

Top image: The nastiest computer-art rendering of the Omicron variant thus far, via Uma Shankar Sharma/Getty Images

This post has been updated to include the third case in Colorado.