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Blizzard, winter storm and freezing rain warnings were issued for more than 25 states, from North Dakota and Colorado down to New Mexico, then up through Texas, Kansas and Missouri to the Great Lakes region and across Pennsylvania to New England.
The Federal Emergency Management Agency (FEMA) urged residents to prepare in earnest for the fury of the storm as it barrels eastward across the country.
"A storm of this size and scope needs to be taken seriously," said FEMA Administrator Craig Fugate, who warned that "it's critical that the public does its part to get ready."
Fugate urged residents in storm affected regions to "check on your neighbors, especially the elderly and young children -- those who can be most vulnerable during emergencies."
Scores of schools and government offices in US Midwest were closed Monday as freezing rain began to fall, threatening to turn roads into deadly ice rinks and down power lines and trees.
Airlines warned of significant delays and cancellations and offered customers a chance to rebook flights at no fee.
The worst of the storm was expected Tuesday as a large amount of moisture sucked up from the Gulf of Mexico feeds the huge system and is transformed into snow and thunderstorms.
Powerful winds and heavy snow could create white-out conditions and drifts as high as six to eight feet (1.8 to 2.4 meters), making travel impossible.
"Lurking behind this impressive winter storm is a powerful shot of Arctic air as a frigid surface high drops down from central Canada," the National Weather Service warned.
Wind chills were forecast to drop to 30 to 50 below in Colorado, Wyoming, the Dakotas, Kansas, Idaho and even parts of Texas.
Officials warned the public to stay at home rather than try to brave the crippling storm.
"It doesn't take a whole lot to make everything slick and if roads aren't treated they're going to get icy and then it's going to snow on top of that, which is going to make matters worse because you can't see the ice," Pat Slattery, a spokesman for the weather service, told AFP.
"One of the concerns about the freezing precipitation is if it gets heavy and starts taking down power lines and trees because people have no way to keep their homes warm, and a bitter cold will follow right on the heels of the snow and freezing rain."
As much as 18 inches (45 centimeters) of snow was expected in the Chicago area and officials warned that ploughs would not be able keep up, making side streets impassable.
Gusts up to 60 miles per hour could also lead to flooding along the lake shore as waves build up to 25 feet.
Many other areas were predicted to get over a foot (30 centimeters) of snow.
"The east coast will begin to get in on the winter weather action Monday night as the precipitation begins to nose its way over the Appalachians," the weather service warned.
"By Tuesday morning the mid-Atlantic and southern New England states will be in the mix."
The storm arrived just days after a rare thunder-snow storm paralyzed air and ground travel from Washington to Boston.
After building up early Wednesday with ice and freezing rain, last week's storm blindsided the US capital at the height of the evening rush hour Thursday, not even sparing President Barack Obama, who faced travel delays upon returning from a day trip to the US Midwest.
There was no word yet on whether the latest storm would impact Groundhog Day on Wednesday, when the nation watches Phil, the weather predicting groundhog in Punxsutawney (Pennsylvania), to see if six more weeks of winter are still to come.
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