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Bodies of as many as 46 people, who are believed to be migrants, were recovered from an abandoned lorry on the outskirts of San Antonio, Texas, media reports said on Tuesday.
A fire official told BBC 16 people, including four children, had also been taken to hospital.
The survivors were "hot to the touch" and suffering from heat stroke and heat exhaustion, reports BBC.
San Antonio is located 250km from the US-Mexican border.
This is considered as a major transit route for human traffickers, media reports said.
San Antonio Mayor Ron Nirenberg reacted to the incident and tweeted: "Migrants seeking asylum should always be treated as a humanitarian crisis, but this evening we're facing a horrific human tragedy."
Migrants seeking asylum should always be treated as a humanitarian crisis, but this evening we're facing a horrific human tragedy.
— Mayor Ron Nirenberg (@Ron_Nirenberg) June 28, 2022
More than 40 hopeful lives were lost. I urge you to think compassionately, pray for the deceased, the ailing, and their families at this moment.
"More than 40 hopeful lives were lost. I urge you to think compassionately, pray for the deceased, the ailing, and their families at this moment," he said.