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An Associated Press photographer near the port saw people lying injured on the ground, and hospitals called for blood donations, but exact casualties were not immediately known.
Miles from the scene of the blast, balconies were knocked down, ceiling collapsed and windows were shattered.
The cause of the blast was not immediately clear. It came at a time when Lebanon is passing through its worst economic and financial crisis in decades.
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Online video showed a column of smoke rising from the port area from what appeared to be an initial explosion, followed by a massive blast that sent up a mushroom cloud and a shock wave racing over the city.
Some local TV stations reported the blast was at Beirut’s port inside an area where fireworks were stored.