A huge section of the Morandi Bridge collapsed at mid-day over an industrial zone, sending tons of twisted steel and concrete debris onto warehouses below. Photos published by the Italian news agency ANSA showed a massive, empty gulf between two sections of the bridge.
There was initial confusion over the exact death toll and officials were still searching for people in the rubble. Firefighters said two people were pulled alive from vehicles in the rubble and transported by helicopter to a hospital.
The head of Italy's civil protection agency, Angelo Borrelli, told reporters at a news conference in Rome that the collapse left 20 people dead and 13 injured. He said all the victims appeared to all have been in vehicles that plunged from the bridge.
Earlier, an Italian transport official, Edoardo Rixi, had said that 22 people were killed and 13 injured in the collapse.
Borrelli said 30-35 cars and three heavy trucks were caught up as an 80-meter (260-foot) stretch of the bridge collapsed.
Borrelli said highway engineers were checking the safety of the bridge at other points and that some areas were being evacuated as a precaution. He said they were still trying to figure out the reason for the collapse.
"You can see there are very portions big of the bridge (that collapsed). We need to remove all of the rubble to ascertain that all of the people have been reached," Borrelli said, adding that more than 280 rescue workers and sniffer dogs units are at work. "Operations are ongoing to extract people imprisoned below parts of the bridge and twisted metal."
Video of the collapse captured the sound of a man screaming: "Oh God! Oh, God!" Other images showed a green truck that had stopped just short of the gaping hole in the bridge and the tires of a tractor trailer in the rubble.
Firefighters told The Associated Press they were worried about gas lines exploding in the area from the collapse.
Italy's transport minister, Danilo Toninelli, called the collapse "an enormous tragedy."
News agency ANSA said Prime Minister Giuseppe Conte will travel to Genoa later Tuesday. "We are following minute by minute the situation," Interior Minister Matteo Salvini said on Twitter.
The disaster occurred on a highway that connects Italy to France, and northern cities like Milan to the beaches of Liguria.
It came on the eve of a major Italian summer holiday on Wednesday called Ferragosto, which marks the religious feast of the Assumption of Mary. It's the high point of the Italian summer holiday season when most cities and business are closed and Italians head to the beaches or the mountains. That means traffic could have been heavier than usual on the Genoa highway.
The Morandi Bridge is a main thoroughfare connecting the A10 highway that goes toward France and the A7 highway that continues north toward Milan. Inaugurated in 1967, it is 45 meters (148 feet) high, just over a kilometer (.6 miles) long.
The collapse of the bridge comes eight days after another major accident on an Italian highway, one near the northern city of Bologna.
In that case, a tanker truck carrying a highly flammable gas exploded after rear-ending a stopped truck on the road and getting hit from behind itself. The accident killed one person, injured dozens and blew apart a section of a raised eight-lane highway.
This story corrects the height of the bridge to 45 meters (147 feet).
Simone Somekh contributed from Rome.
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