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All New Yorkers will need to be vaccinated if they want to go to work, the city's mayor has announced.
Public sector employers already have to be inoculated, but the mandate will now be extended to all private sector employees, Bill de Blasio told MSNBC.
The policy will take effect on 27 December, he said.
"We in New York City have decided to use a pre-emptive strike," said Mr de Blasio, who leaves office in early January.
"We've got Omicron as a new factor, we've got the colder weather which is going to really create new challenges with the Delta variant, we've got holiday gatherings," he said.
"Vaccine mandates are the one thing that breaks through."
He said New York would be the first US city to mandate vaccines for private sector workers.
A mandate for public sector workers which came into force earlier this autumn met vocal resistance, and led some employees to leave their jobs. However, rates of vaccination rose in response to the policy.
Ten cases of the new Omicron variant, which is thought to be more transmissable than previous strains of Covid, have been identified in New York City and the immediate surrounding region.
One person attended an anime convention in Manhattan on 23 November, mixing indoors with hundreds of other attendees.
Mr de Blasio said it should be assumed that there was already community spread of the variant in New York.
Describing the mandate for private sector workers as a "first in nation" strategy, he urged other cities to follow suit.
"This would be my advice to mayors, governors, CEOs all over the country - use these vaccine mandates. The more universal they are, the more likely employees will say, OK it's time I'm going to do this, because you can't jump from one industry to another or one company to another. It's something that needs to be universal to protect all of us."
Mr de Blasio said he expected to receive cooperation from New York's business community, in the same way they had adopted and enforced vaccination requirements for eating indoors at restaurants, events and gyms.
President Biden's nationwide policy to mandate vaccines for the private sector has been stalled by opposition in Congress and the courts.