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The southern cold snap is part of an arctic front that has put much of the Northeast and northern Plains under warnings and advisories for dangerous wind chills. Temperatures in parts of those regions could feel as cold as minus 34 Celsius, the National Weather Service said.
Schools and government offices across a wide swath of the country were closed. Airlines canceled or delayed thousands of flights, and officials closed roads as conditions worsened.
North Carolina and South Carolina were expected to get the most snow, while the heaviest ice accumulation was forecast from Louisiana to the Carolinas, the weather service said.
Temperatures between 10 and 20 degrees colder than normal were expected to continue for much of the eastern United States. In Washington, DC, the National Gallery's skating rink shut down, with officials saying it was too cold for skaters to be out on the ice.
"We're getting a bit of everything," said Jody White, a police sergeant in Opelousas, Louisiana. "It's cold. The sleet is coming down in patches."
In Alabama, two people died and five others were hospitalized after a seven-car crash on an iced-over bridge near Montgomery, said Robyn Litchfield, an Alabama Department of Public Safety spokeswoman.
Lawmakers in South Carolina canceled this week's session of the state legislature due to weather concerns, and Mississippi Governor Phil Bryant declared a state of emergency for at least three dozen counties.
The storm took a toll on air travel across the region, with more than 3,000 U.S. flights cancelled and hundreds of others delayed, according to flight tracking website FlightAware.com.
In New Orleans, which last got an inch of snow in 2008, freezing rain and sleet were likely through most of the afternoon and would possibly turn into snow in the evening, said Danielle Manning, a forecaster with the National Weather Service in Slidell, Louisiana.
Schools were closed and jury selection in the corruption trial of a former mayor was suspended due to the cold weather. The manager of a popular grocery store said it was packed with shoppers stocking up on food and supplies before it also closed.
"They were buying hurricane stuff, including a lot of spirits, of course," said Edwin Moreno, manager at Dorignac's Food Center in suburban New Orleans.
The bad weather prompted a federal judge in Knoxville, Tennessee, to postpone court proceedings part way through a sentencing hearing for three peace activists, including an elderly nun.
Winter weather advisories were also issued for a wide swath of eastern and central Texas for Tuesday, with predictions of up to 1 inch (2.5 cm) of snow near the state's border with northern Louisiana.
Freezing temperatures and rain snarled the morning commute through large parts of central Texas and Louisiana, where roads and bridges were iced over. Police in Austin, Texas, reported about 100 crashes caused by icy roads but said there had been no fatalities.