"It’s a localized infection," Sam whispered, hopping out of the car to inspect a fallen road worker. "Whatever that smoke was, it changed them."
The black smoke that had roared across the landscape was gone, leaving behind a stillness that felt like a trap. Dean wiped a smear of blood from his forehead, his eyes darting to the tree line. He could still feel the phantom touch of the woman in the black dress, the Mark of Cain gone from his arm but the weight of her words settled deep in his marrow. "Sam," Dean rasped, his voice cracking. "You okay?" [S11E1] Out of the Darkness, Into the Fire
They climbed back into the car, the rumble of the engine the only familiar thing left in a world that had suddenly turned alien. As they drove toward the nearest town, Superior, Nebraska, the signs of the "Darkness" began to manifest. It wasn't monsters in the shadows; it was a sickness. "It’s a localized infection," Sam whispered, hopping out
If you want to explore more about this specific era of the show: The psychological bond between Sam’s secret struggle with the Rabid infection Castiel’s torture at the hands of the angels He could still feel the phantom touch of