"It looks like a bomb exploded," one witness told Action News.
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Viewer video: South Philadelphia explosion, fire leaves two people trapped
It happened around 11:40 a.m. Thursday on the 1400 block of South 8th Street near Reed. Fire officials said the gas-fed fire was brought under control at about 2:45 p.m. after it raged for hours.
"We believe now...we have a pretty good confidence that there are two people who are missing and presumably deceased," said Fire Commissioner Adam Thiel on Thursday evening during a news conference.
Philadelphia fire commissioner provides update on house explosion
Google Street View shows what the South Philadelphia neighborhood looked like before the explosion.
Chopper 6 over the scene showed flames shooting through the roof at about noon.
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Rowhomes burn in South Philadelphia
Authorities said they responded to the scene after they received multiple calls about a house explosion and the smell of "possible gas."
A second-alarm was struck. More than 100 Philadelphia firefighters were called to the scene.
Officials said three or four buildings were involved and that two homes collapsed following the explosion. Officials said they are not sure how many others may be injured because they have not yet been able to make it through all the debris.
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As the Action Cam arrived at the scene, a woman who appeared to be crying was being escorted away by firefighters.
Mike Seccia, who owns the nearby Cosmi's Deli, said the explosion was "the loudest bang he's ever heard."
He gave his employee a fire extinguisher and they headed to the scene.
"The small fire then became one of the worst spectacles I have ever seen," Seccia said.
Seccia said they saw a man caught in the rubble, but they couldn't get to him.
"They couldn't get him and within seconds, the flames started coming from the second floor and they had to get out of there," he said.
Thiel said crews were doing everything they could to help save others.
"We're not giving up. We don't ever give up," he said.
Brian Contrsciane also tried to help after the explosion leveled his neighbors home, spilling fiery debris into the street.
"We were trying to pull the guy out but so much rubble had fallen we couldn't get leverage to pull him out," he said.
The rescue effort, now a recovery operation is a difficult thing to hear for neighbors who tried to help.
"I'm a little shook up. It's a weird thing to see somebody try to pull him out and the house falls on him," one neighbor said.
Commissioner Thiel says to even begin removing debris, heavy equipment needs to be brought in and parked right in front of the collapse. But the explosion has compromised the road and now a sinkhole is forming. The road has to have work done on it with new supports.
The cause of the explosion remains under investigation.