The collisions began about 8 a.m. on Interstate 57 as thick fog enveloped the Charleston area, about 150 miles (240 kilometers) south of St. Louis.
Mississippi County Coroner Terry Parker confirmed the five deaths and said a mobile morgue has been set up at a funeral home in Charleston, KFVS-TV reported.
Officials did not have an estimate of how many people were injured.
Missouri State Highway Patrol Sgt. Jeff Kinder said about 50 vehicles were involved, including several semitrailer trucks. He said some of the vehicles caught fire but that the fires were extinguished by about 4 p.m. and officials were beginning to tow vehicles away.
“It will be hours, well into the night, before the highway can be reopened,” Kinder said.
The interstate was closed for about 25 miles (40 kilometers) in both directions in Mississippi County from the Missouri-Illinois border to Sikeston, Missouri.
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