A massive snowstorm that has already turned deadly churned up the East Coast on Friday afternoon, forecast to transform into an angry blizzard that could bury the nation's capital under more than 2 feet of snow.
The weekend whiteout, which threatens to be Washington, D.C.'s worst in a century and bring blizzard conditions to Philadelphia and New York, has led to 6,000 canceled flights and caused at least six deaths.
"We see this as a major storm. It has life and death implications. And all the residents of the District of Columbia should treat it that way," Washington, D.C., Mayor Muriel Bowser said.
The main priority, Bowser said, was to keep people safe, from students to commuters to the homeless. Public schools were closed Friday, the Metro will stop operating at 11 p.m. and outreach workers will try to find shelter for people who would otherwise sleep outside. Federal government workers have been told to leave work at noon Friday, just before the front edge of the blizzard is expected to arrive.
READ MORE: Millions Brace for Major Snowstorm
— The Weather Channel (@weatherchannel) January 22, 2016
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The immense and sprawling storm will blast snow across 15 states beginning Friday afternoon and evening and continuing well into Sunday night, forecasters say. That has prompted rare blizzard warnings not only for Washington, D.C., but also Baltimore, New York City, Philadelphia, Trenton, New Jersey, and Long Island, New York.
The storm has killed at least six people, including three in North Carolina who died in traffic accidents on icy roads.
Where there weren't blizzard warnings, there were fears of other dangerous conditions. Various winter weather warnings, watches and advisories were in effect in more than 20 states, from New York to South Carolina to Kansas, the Weather Channel reported. That covers more than 85 million people -- more than a quarter of the U.S. population. Heavy winds and ice in North Carolina and South Carolina could knock out power lines.
The National Weather Service warned of "extremely dangerous travel" conditions and "numerous power outages" across the region. More than 2,500 flights had been canceled as of Friday morning, with thousands likely to follow.
That includes Philadelphia International Airport, which preemptively canceled all Saturday flights in anticipation of up to 18 inches of snow. American Airlines canceled all of its Friday flights out of the Washington, Baltimore and Charlotte, North Carolina, airports.
We will suspend flights at our Dulles hub and other mid-Atlantic airports starting Friday, Jan. 22, at 4 p.m. ET.
— United Airlines (@united) January 21, 2016
Amtrak canceled several national services for Friday, Saturday and Sunday, including Crescent service from New York to New Orleans, Cardinal service from New York to Chicago and Silver Meteor service from New York to Miami.
"This is going to be a legitimate blizzard," said Ari Sarsalari, a meteorologist for The Weather Channel. "Some of these [snow] numbers are absolutely staggering."
Saturday will be "an absolute mess," he added, predicting that travel would be "literally impossible anywhere in the Mid-Atlantic region."
By 3:30 a.m. ET Friday, snow was falling across a crescent stretching from Arkansas through Kentucky and down into North Carolina.
One area where the forecast had changed was New England, which now looked likely to miss out on the snow, save for a possible inch in Boston on Saturday, according to Weather Channel lead forecaster Michael Palmer.
"I think the folks up there are probably used to that, anyway," he said.
See President Obama's motorcade slip and slide in the snow:
A day after a mere inch of snow paralyzed Washington, transit authorities shut down the D.C.-area Metro system -- the nation's second-busiest mass transit network -- for the entire weekend. No trains will run after 11 p.m. Friday, and buses will be benched at 5 p.m., during the heart of the evening rush hour.
New York Mayor Bill de Blasio, however, suggested his city is made of sterner stuff and said there were no plans yet to close the subway. Latest forecasts predicted a range of 8 to 12 inches of snow there.
Many areas were under blizzard advisories because of strong winds forecast for the weekend. Forecasters warned that 60-mph gusts could blow wet, heavy snow into trees, power lines and transformers, presaging widespread power failures in the East from North Carolina to New England.
And because a full moon will swell tides this weekend, "moderate to major" coastal floods could be in store from Maryland and Delaware to Connecticut -- including coastal New York -- said Michael Lowry, a storm surge specialist for The Weather Channel.
The storm is expected to reach so far south that it could affect Sunday's National Football Conference championship game between the Carolina Panthers and the Arizona Cardinals in Charlotte.
A forecast of freezing rain Friday led the city to cancel a pep rally for the team, and snow up to 3½ inches is forecast for Saturday, when the Cardinals are scheduled to fly to Charlotte ahead of Sunday's game.
Charlotte-Douglas International Airport had canceled almost 400 arrivals for Friday and about 50 so far for Saturday, but the Cardinals said that for now, they didn't expect to be delayed.
But for the team's fans, getting to the game could be tricky.
"I'm a little nervous," Tyler Vasquez of Phoenix told NBC station KPNX. "I have yet to get an email from my airline, [but] a lot of people in our group that we have that are going on this trip have posted, 'I've got this email or my flight's been canceled.'"
If necessary, Vasquez said, he'll fly to Atlanta on Saturday and try to make the 4½-hour drive to Charlotte.
Meanwhile, in Chesterfield County, Virginia, school officials got creative in announcing the cancellation of classes with a district-wide music video.
The weather system produced entirely different effects further south, with a "possible tornado" causing major damage to two homes and downed trees and power lines in Mississippi's Lamar County late Thursday, according to The National Weather Service.
In Florida's Calhoun County, radar detected "tornado debris signature" at 4:50 a.m. ET, although both twisters were yet unconfirmed.
Thunderstorms were also possible across Georgia, Alabama and South Carolina, sparked by the same warm air from the Gulf of Mexico that was clashing with cold air further north and producing all that snow.
Learn more about the wild weather in Mississippi: