Smiting sickness is caused when angels release an immense force of power on Earth, causing fallout to poison the surrounding area for some miles. If a human ventures into an area that has fallout, they will become disoriented and begin vomiting the closer they get to ground zero. The symptoms are so severe that they cannot be healed by an angel, with the effects of the sickness becoming worse the closer a human gets, Lot's wife having turned to salt due to her proximity to a smiting event. Smiting of this magnitude rarely happens on Earth, with the destruction of Sodom and Gomorrah and the two attacks on Amara being the only known cases.
Though a similar smiting was launched against Amara in 11.22 We Happy Few, there was no sign of smiting sickness afterwards in 11.23 Alpha and Omega with the Winchesters and Rowena MacLeod being able to stand in close proximity to the ground zero without suffering any harm from it due to God protecting them.