More than half the continental United States will have below-average temperatures Friday. Temperatures will be 20 to 30 degrees below average in locations stretching from the Montana to South Texas.
Dangerous wind chills could yield temperatures as low as 40 degrees below zero in the Northern Plains on Friday.
Snow contributed to a 30-car pileup on Interstate 96 in Fowlerville, Michigan, on Thursday. Police reported two deaths.
In Ohio, snowy conditions led to a more than 50-vehicle pileup on I-90 in Lake County, officials there said. The Lake County Sheriff's Office said multiple people were trapped in their cars.
Authorities said at least 19 people were injured, including five seriously, in the crash between Route 44 and Vrooman Road in the area of Painesville, CNN affiliate WJW
Greg Carmichael, a passenger on a Greyhound bus involved in the pileup, told WJW he was bound for Buffalo when a semi hit the bus from behind about an hour into the ride.
"It just was a domino effect, everybody crashed," he said.
Carmichael added: "There was some guy that was literally buried under his truck."
Several passengers on the bus were among those treated for serious injuries, WJW reported.
In Portland, Oregon, state police said icy conditions contributed to a crash that killed one person Thursday morning on Highway 99 in Benton County, CNN affiliate KOIN
Cold air will push into the Northeast and Southeast on Friday, with subfreezing low temperatures reaching the Gulf Coast by Saturday morning.
Another, even colder air mass is forecast to enter the Midwest and Northeast late next week.
According to meteorologist Ryan Maue, the upper-level atmosphere configuration looks very similar in scale and magnitude to the January 2014 "polar vortex
" that left the country in below-average temperatures for days. Luckily, next week's cold spell will last only a few days.
Lake-effect snow started along the southern and eastern shores of the Great Lakes on Thursday and is expected to last until early Saturday. More than 5 million people are living in areas covered by a lake-effect snow warning, watch or advisory.
The heaviest snow bands could bring over a foot of accumulation in the Upper Peninsula of Michigan and nearing 2 feet in parts of upstate New York.
A strong storm entering the Northwest will bring more snow on Friday, not only to the mountains but to lower elevations as well.
About 10 million people are under winter storm warnings and winter weather advisories in the West.
Snow will spread throughout the region, with feet of accumulation expected in the mountains. Portland, Oregon, and Seattle will get a couple of inches.
After exiting the West, this system will leave a swath of snow as it passes over the Northern Plains and southern Great Lakes this weekend.