The chain-reaction pileup occurred about 9:30 a.m. at Oak Hill Road and left most of the victims with moderate to minor injuries, according to the county fire department, which was performing triage at the crash site.
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The majority of the patients declined to be transported to a hospital, according to fire officials.
Weather was a contributing factor to the collision, investigators said. Visibility was poor in the area due to heavy fog.
A Caltrans camera showed a miles-long backup of traffic at the scene.
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It was unclear when the southbound side of the interstate would be reopened. Drivers were urged to use Ranchero Road as an alternative route.
DEVELOPING: More details will be added to this report as they become available.