As they are about to leave, a Gunship guns down Daina and her associates, allowing Isaac to escape. Upon his arrival, two guards seize Isaac as Daina reveals that she is a Unitologist sent to “recover” Isaac, claiming that he is responsible for building the Marker that is causing the current infestation and that they need him to build more.

Ignoring Stross, Isaac fights his way across the city, making his way to Daina. He is also contacted by another patient, Nolan Stross, claiming he and Isaac can destroy the Marker. He is later contacted by a woman named Daina Le Guin, who guides him to her location. However, before he can remove the straitjacket, Franco is killed and transformed into a Necromorph, leaving Isaac to escape on his own. Isaac Clarke has no memory of the last three years, having just been released by Franco, the protagonist of Dead Space: Ignition.

The game begins in a hospital on the Sprawl, a densely populated metropolis built on a shard of the moon Titan, Saturn's largest moon.

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