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"It slimed me! God damn it! I'm covered in goo!"
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Having just survived an encounter with the Infected of epic proportions, the Survivors prepare themselves on a rooftop in Fairfield, only to hear a helicopter flying overhead announcing evacuation at the city's Mercy Hospital. Already acquainted with one another, the Survivors make haste to the hospital in question, and, after fending off the Infected, are picked up by the helicopter's pilot.
Just a few minutes after escaping in the helicopter, the pilot turns into an infected. After Zoey shoots the newly turned pilot, the helicopter crashes in the outskirts of Riverside, and the Survivors head off in search of a rescue vehicle. They finally discover an armored truck in a car garage and use it to escape.
The Survivors are once again stranded when they find that the bridge is destroyed. After abandoning the truck, they head into the town of Riverside. Along the way they find a crazy guy in a church and finally find a boat house at a lake. The Survivors use this to call for rescue from John and Amanda Slater, two people with a nearby boat.
The Survivors are left to die by the Slaters in a city called Newburg, where the team takes shelter in a rooftop greenhouse. A low flying C-130 plane gives them hope that the local airport might still be running evacs. Upon reaching the airport, the Survivors must defend it while the pilot prepares the plane for flight before escaping.
When the Survivors reach Allegheny National Forest, they decide to head towards a military rescue outpost. Upon reaching a farm house, the Survivors use a radio to request rescue from the military. They then hold off the infected until an armored personnel carrier picks them up and takes them to Millhaven's military base.
The military locks up the Survivors and a doctor explains to them that they are carriers. When Lieutenant Mora sounds the base's alarm to command retreat, the infected attack. Louis saves the lives of soldiers Jeff and Anne, who in return allow them to carry weapons to fight the infected with. Meanwhile, Bill, Zoey, and the doctor head towards the armory as well. They all meet up there and head across the base courtyard, towards an old train. When they get there, Jeff and Anne leave to go with the rest of the soldiers, and the Survivors, with the doctor, head towards the train. When they reach it though, the doctor is stopped and killed by Special Infected, and the Survivors head south on the train.
The train comes to a halt in Rayford, Georgia, where the Survivors' new plan is to find a boat and travel somewhere free of the infected. However, on the first boat, Louis finds a dozen Witches on board who almost rip his leg off. They find a different boat, but when they try to raise the bridge that's in the way, one of the generators breaks down, making the bridge stop half way up. Now the biggest horde they have ever seen plus 3 tanks are right in front of the Survivors. Seeing that there's only one way this can end, Bill jumps down and fights his way to the generator that stopped and turns it back on, making sure that the bridge raises with the other 3 Survivors on it, but stranding himself in the process, and committing the ultimate sacrifice. A short time later, the remaining three Survivors encounter four other Survivors who arrive in a racing stock car. They help them cross the bridge and see them on their way. When the other Survivors have left, Louis, Zoey, and Francis take the sailboat to inhabit islands far away from all their troubles, and rest out until the apocalypse is over.