As many as 29 people were reported injured in the crash, which occurred at around 9 am on busy Via Cassia in the north of Rome.
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Between five and nine people were rushed to hospital with serious injuries, though none are said to be in critical condition.
Pictures showed the bus, a 301, with its windscreen smashed and the front partly wrapped around a tree on the side of the road.
#ATAC prime foto dello schianto di un bus poco dopo le 9 sulla Cassia, (altezza Via Oriolo).
Il bus era in servizio sulla linea 301. Si registrano diversi feriti. Ambulanze sul posto#UltimOra #Roma pic.twitter.com/t3uQynXxMC
— Mercurio Viaggiatore (@MercurioPsi) October 16, 2019
Public transport company Atac says it is investigating what caused the crash, which it called a “serious incident”.
The vehicle involved is 12 years old, while the driver has been in service since 2007, the company said.
The road was partially closed and traffic was being diverted around the site of the crash on Wednesday afternoon, with severe delays on the bus lines 301, 201 and 223 as a result.
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It's just the latest problem for Atac, which has lost more than 20 buses to spontaneous fires this year alone.
Three of the company's managers are also currently under criminal investigation over dangerously neglected escalators in the capital's metro system, which investigators found to pose an urgent hazard to public safety. Several metro stations have been ordered closed for months at a time while the creaking infrastructure is repaired.