Croatoan
The Croatoan virus is demonic in origin, and causes a murderous rage in the people in infects. It is transmitted through blood to blood contact.
Sam is immune to its effects.
It is a key tool in the plans for the Apocalypse.
See also: Zombie
2.09 Croatoan
Following a vision of Sam's, Sam and Dean travel to River Grove, Oregon where people are overcome with a murderous rage. Sam and Dean save A local doctor studies the blood of an infected person, noting that there appears to be traces of sulfur in the blood, leading Sam to further suspect demonic intervention. The virus is transmitted via exchanging blood, but the sulfur does not manifest in the blood until four hours after infection.
Sam speculates that it could be related to a theory in John's Journal, that Croatoan - a word they find carved into a telephone pole, is the name of a demon associated with plague and pestilence. Sam calls what's going on "demonic germ warfare".
Sam says, "I've been pawing through Dad's journal, I found something about the Roanoke Colony. Dad always had a theory about 'Croatoan'. He thought it was a demon's name, sometimes known as 'Deva', sometimes 'Resheph', a demon of plague and pestilence."
Duane Tanner, the man Sam saw in his vision and whose family Sam and Dean first encountered exhibiting signs of infection, turns up at the medical centre, claiming to have been out of the town fishing and just returned. The medical centre occupants suspect he might be infected, and they restrain him by tying him to a chair.
Recognising the scene from his vision, Sam tries to convince Dean not to kill Duane, as they don't know yet whether he's infected with the Demon virus or not. Dean locks Sam in a room to stop him from preventing the killing, but Dean is unable to follow through anyway.
A nurse deliberately infects Sam, and he resigns himself to dying but doesn't show any symptoms. Five hours later, the doctor announces that there is no trace of the virus in Sam's blood. All the remaining townsfolk have disappeared.
At the end Duane Tanner communicating with Azazel via the Goblet of blood reports that "The Winchester boy is immune" (to the virus). Considering Sam's vision led them to River Grove, it's implied that this 'demon virus' is the work of the Yellow-Eyed Demon.
5.04 The End
In 2012, Lucifer releases the the Croatoan virus in order to wipe out humanity. In 2014, many have been infected and died. Infected zones are quarantined and the military kills infected on sight. President Palin orders the bombing of Dallas following an outbreak.
In 2014, Dean leads a small group of survivors, and is trying to kill Lucifer.
5.20 The Devil You Know
Two Scientists are discussing about the Swine Flu epidemic happening. A Demon possessing a janitor tells them he's seen the Vaccine and is saying he's running the experiment and injects it on one of the scientists and knocks the other down, he than locks and traps them in the room. The Scientist injected with the "vaccine" awakes seeminlgy different and kills the other scientist. The Demon Janitor states "it works". Suggesting that the vaccine is the Croatoan virus. It is guessed that spreading the Swine Flu disease and giving out the *Vaccine* is Pestilence's and the demons' plan.
