The variant is expected to become the "dominant strain" in the coming weeks, CDC Director Dr. Rochelle Walensky said on Friday.
And after nearly two years of a pandemic that has caused more than 800,000 deaths in the US and overloaded hospitals, the omens aren't favorable for the next few months, experts say.
"Even if (Omicron) is less virulent than earlier strains, if we have a point where we're seeing a half-million cases a day or more, we are going to swamp our hospitals -- even with a relatively low rate of hospitalization," said CNN medical analyst Jonathan Reiner, a professor of medicine and surgery at George Washington School of Medicine & Health Sciences. "When you have that kind of denominator, our hospitals will be completely underwater as they are in some parts of the country."
Dr. Peter Hotez, professor and dean of tropical medicine at Baylor College of Medicine, told CNN's Jim Acosta Saturday, "We are going to see a lot of health care workers get sick," pointing to the potential for breakthrough infections.
"Even though they're not going to be severely ill, they're going to be knocked out of the health care workforce," he said. "And that's going to present yet another big stressor on the system."
It's still too soon to assume Omicron will cause milder disease, according to Dr. Francis Collins, director of the National Institutes of Health.
"We still don't really know -- and there's some controversy about this -- whether Omicron causes the same kind of severity of disease or whether it's a somewhat milder form of the illness," Collins told CNN's Anderson Cooper.
Data from two weeks of South African cases appeared to indicate Omicron was milder in severity. The CDC said last week it looked at 43 cases and most of those people had mild symptoms. Most were vaccinated, with about a third of the total group boosted.
But UK epidemiologists said this week they found no evidence Omicron is causing milder disease there, although the Imperial College London team also said there was not much data to go on yet.
However, it's "clear that Omicron is an extremely contagious variant, that it doubles every two to four days," Collins said.
"The problem, of course, is if this is so infectious -- and we might see hundreds of thousands of cases every day, maybe even a million cases in a day from Omicron -- even if it's a little less severe, you are going to have a lot of people in the hospital and our hospitals are already really stretched with Delta, especially in the northern part of the country," Collins said.
"What we would like to see, though, is as many people as possible protecting themselves with vaccines and, especially, with boosters, in order to limit the consequences," he said.
Overall, the US on Friday was averaging 121,707 new Covid-19 cases each day, according to data collected by Johns Hopkins University. Fourteen states saw an uptick of at least 10% in cases over the past week compared to the previous week, the data shows.
About 68,900 Americans are hospitalized with Covid-19, according to data from the US Department of Health and Human Services. More than 20% of all ICU beds in use are occupied with Covid-19 patients, the data shows.
California health officials said Friday they were seeing hospitalization numbers begin to trend upward, stressing the need for vaccinations and booster vaccines. In New York, officials said they're seeing the highest hospitalization rate they've recorded in months, with Gov. Kathy Hochul noting that the staff shortages will weigh into potential new restrictions.
On Thursday, New York state had the highest single-day count of new cases with 21,027, according to data released Friday.
In New Jersey, "we're seeing long lines outside of our testing clinic, more demand than we've seen in many months for testing, because folks are getting sick," Dr. Shereef Elnahal, president and CEO of University Hospital in Newark, told CNN's Amara Walker.
Hospitalizations have doubled over the last two weeks, he said, and although 46% of those hospitalized earlier this week had been vaccinated, they had not had a booster shot.
People not only need to get vaccinated, but they also need to get a booster, Elhahal said, "because what we're seeing is just not sustainable."
Dr. Marc Gorelick, who heads Children's Minnesota hospital, said the facility is already struggling to cope with the numbers.
"When you're on top of a surge where you're already at 90%, 95% capacity, those extra ... preventable Covid patients coming in are the thing that pushes the system to the brink. And that's what we're seeing here in Minnesota," Gorelick told CNN's Kate Bolduan on Friday.
It got so bad that hospital leaders in Minnesota took out a full-page newspaper ad this week to say they were overwhelmed by the pandemic.
"It feels like you are drinking from a fire hose with no way to control that flow," Dr. John Hick, an emergency physician at Hennepin Healthcare in Minnesota, told reporters Tuesday. "I have been practicing for 25 years in the emergency department, and every shift I am working these days is like the worst shift in my career."
In Oregon, officials forecast a grim early 2022.
"We can expect a surge in Oregon hospitalizations by mid-January, with infections that begin sooner than that," said Dr. Peter Graven, a data scientist for Oregon Health and Science University. "Combined with its heightened transmissibility, we expect Omicron will generate a large increase in the number of Oregonians that will become severely ill and likely need a hospital."
The US has fully vaccinated just over 61% of its total population, with about 29% having received a booster dose, according to the latest CDC data. According to CNN's analysis, at the current pace it will take more than two months for half of US adults to get a Covid-19 booster.
As cases climb and anxiety about Omicron grows, school officials and event organizers across the country -- but particularly in the Northeast -- have moved to reinstate restrictions or cancel events altogether.
Harvard University on Saturday became one of the latest schools to announce a shift to remote learning for some in response to "the rapid rise in COVID-19 cases locally and across the country, as well as the growing presence of the highly transmissible Omicron variant."
In a letter to the community, university officials said students must be authorized by their schools to return to campus for the first three weeks of January, while faculty and staff who can should work remotely. The aim, the letter said, was to "reduce density on campus by moving much of our learning and work remotely."
In Maryland, Prince George's County Public Schools will shift to remote learning beginning December 20 through January 18 due to "the stark rise in COVID-19 cases throughout (their) school system," according to a Friday statement from the school district's Chief Executive Officer Monica Goldson.
The University of Maryland canceled its winter commencement ceremonies, noting that all social gatherings on campus where mask wearing could not be strictly enforced should follow suit. Final exams will be conducted in person, but students and faculty will be required to wear a university-provided KN95-rated mask, it said.
In New York, the Radio City Music Hall's Rockettes canceled their "Christmas Spectacular" show. And "Saturday Night Live" announced in a tweet it was canceling its live studio audience for Saturday's taping of the show.
Michigan State University and New York's Hofstra University both said Friday that students and staff will be required to have booster shots for start of the spring semesters.
In Hawaii, a ceremony that was slated to celebrate the end of the state's National Guard's Joint Task Force on Covid-19 was canceled, and the governor's office said the task force is being reestablished due to Omicron.