After the mark of cain was taken off of Dean, Sam and him celebrate for what feels like seconds before the ground breaks and 'the darkness' is released after Dean chose to kill death over his baby brother. Sam and Dean drive further and further only to see depression and strife, everyone who was in the vicinity of the black smoke 'the darkness' released, was either dead or killed by mutated humans that the smoke created.

Those who survived the black smoke, where turned into blood hungry monsters with black veiny necks being the only tell-tale sign. As Sam and Dean are headed to leave the hospital after they rescue a survivor deputy and a man with his newborn, the ancient 'darkness' would come to find them.