Officials warned of nearly instant frostbite as temperatures in the region plunged below zero Wednesday. In nine states, mail delivery has stopped.
About 212 million people - or 72% of the continental USA population - will see temperatures drop below freezing over the next few days.
Over 1,440 flights have been canceled at O'Hare Airport, and over 250 flights have been canceled at Midway airport.
In Illinois, at least 144 people visited hospital emergency rooms for cold-related injuries over two days. Chicago's forecast low temperature Thursday morning is within the margin of error of its lowest on record, minus-27 set on January 20, 1985. Its daytime high Wednesday is forecast to be 15 below zero. The overnight low in Boston was at minus 5, according to the National Weather Service. Officials said weather was a factor.
This time, it is being said, higher than usual temperatures in the Arctic region have forced the bitterly cold winds to travel south, affecting the temperatures in the U.S. and Canada.
While the adjustment could be hard, not many people will miss the cold after at least 160 record lows were set throughout the Midwest and Northeast in recent days.
Frigid weather has already started to hit the Dakotas, Minnesota, Wisconsin and IL. It said it typically operates 55 trains daily to and from the Chicago hub. "Best thing you can do is limit your time outside", the office said.
Hennen described it as the "coldest air in a generation".
Thousands of flights to and from Chicago have been cancelled as temperatures have dropped to an "life-threatening" -21 degrees Celsius.
In central Iowa, wind chills are also a major concern.
The cold temperatures are caused by Arctic air masses drifting farther south than usual, bringing biting winds that are pushing wind-chill temperatures in regions of a dozen states as low as minus 40 degrees Fahrenheit (minus 40 degrees Celsius).
According to reports, the last time the U.S. was this cold was in 1994.
Wind chill refers to how cold people and animals feel when they're outside, according to the weather service. The extreme cold was "a scary situation", because much of the housing is of poor quality, said Chris Fairbanks, energy assistance program manager for the White Earth Band of Ojibwe in Minnesota.
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And that doesn't include wind chill, which in northern IL made the air feel as cold as negative 57 degrees (negative 49.4 Celsius).
Frostbite is caused by freezing of the skin and underlying tissues. Severe cases can kill body tissue. But students headed back to school Thursday in eastern North Dakota, where the weather was forecast to crawl out of double-digit sub-zero temperatures.
The North Dakota Highway Patrol said it also issued a travel alert for southeast North Dakota due to blowing snow. The condition results in a loss of feeling and color in affected areas. "Motorists are encouraged to wear seat belts, reduce speeds and drive according to the conditions", it said.
On Thursday evening, a snow squall was issued for NY by the National Weather Service.
The cold weather was even affecting beer deliveries, with a pair of western Wisconsin distributors saying they would delay or suspend shipments for fear that beer would freeze in their trucks.
The lowest temperature recorded that day was minus 40 in International Falls, Minn., just south of Canada.
"We are not used to this".
"Stay inside", Brunette said, warning of the heightened risks of frostbite and hypothermia.
States of emergency have been declared from Wisconsin and MI, down to Alabama and Mississippi.
"Such widespread, extreme conditions have not occurred in MI for many years".
Of the 23 deaths linked to this week's extreme weather, three were in New York's Erie County and two in Chicago.
Companies told their workers to stay home. He didn't have keys to the home and was unable to enter after being dropped off that morning. No foul play was suspected, police said.
And in IL, a man died Monday in a crash involving a village plow truck and a pedestrian, Libertyville police said.