There’s two views on how greyscale will affect the future plot of ASOIAF. The first view, which I don’t agree with, is that it will be solely personal and localized only to Jon Connington, spurring his actions in TWOW and ADOS (if he lives that long).
The second view – well, that theory says JonCon is just the start.
“Ser Jaime, I have seen terrible things in my time,” the old man [Pycelle] said. “Wars, battles, murders most foul… I was a boy in Oldtown when the grey plague took half the city and three-quarters of the Citadel. Lord Hightower burned every ship in port, closed the gates, and commanded his guards to slay all those who tried to flee, be they men, women, or babes in arms. They killed him when the plague had run its course. On the very day he reopened the port, they dragged him from his horse and slit his throat, and his young son’s as well. To this day the ignorant in Oldtown will spit at the sound of his name, but Quenton Hightower did what was needed. Your father was that sort of man as well. A man who did what was needed.”
–AFFC, Jaime I
“How did she die?” Tyrion knew that she was dead; no man spoke so fondly of a woman who had abandoned him.
“A Braavosi trading galley called at Pentos on her way back from the Jade Sea. The Treasure carried cloves and saffron, jet and jade, scarlet samite, green silk… and the grey death. We slew her oarsmen as they came ashore and burned the ship at anchor, but the rats crept down the oars and paddled to the quay on cold stone feet. The plague took two thousand before it ran its course.”
–ADWD, Tyrion II
“And the daughter… her face…”
“The grey death is what we call it.”
“It is not always mortal in children.”
“North of the Wall it is. Hemlock is a sure cure, but a pillow or a blade will work as well. If I had given birth to that poor child, I would have given her the gift of mercy long ago.”
This was a Val that Jon had never seen before. “Princess Shireen is the queen’s only child.”
“I pity both of them. The child is not clean.”
“If Stannis wins his war, Shireen will stand as heir to the Iron Throne.”
“Then I pity your Seven Kingdoms.”
“The maesters say greyscale is not—”
“The maesters may believe what they wish. Ask a woods witch if you would know the truth. The grey death sleeps, only to wake again. The child is not clean!”
“She seems a sweet girl. You cannot know—”
“I can. You know nothing, Jon Snow.” Val seized his arm. “I want the monster out of there. Him
and his wet nurses. You cannot leave them in that same tower as the dead girl.”
Jon shook her hand away. “She is not dead.”
“She is. Her mother cannot see it. Nor you, it seems. Yet death is there.”
–ADWD, Jon XI
So, two characters in AFFC/ADWD relate tales of grey plague epidemics that killed thousands… and Val is certain that Shireen is not cured, merely a dormant greyscale vector… and Jon Connington got infected with greyscale in the Sorrows and has returned to Westeros… That’s four pieces of evidence that hint that something terrible is coming. The only question in my mind is just how widespread a killer it’s going to be.
Now, I’m not fully certain of the theory that Patchface is going to kill Shireen and let the greyscale out (although I am unfortunately sure that Shireen is doomed and I am tremendously creeped out by Patchface nevertheless), because, well, the North does have enough problems. Between winter’s cold and blizzards, the Others and their wights, and the coming fall of the Wall, a grey plague would just be adding insult to injury. And while I wouldn’t put it past GRRM to pile one horrible thing on top of another, after a point I’m not sure there’d be enough people left in the North to kill.
But the South… well, that’s got Aegon’s invasion on the east coast, and the Ironborn invasion on the west coast, and dragons are coming, and wildfire is going to take out King’s Landing. But there’s a large central section that’s too south for winter to be as big a killer as it is in the north, unlikely to be reached by Others and wights (if the theory that they’ll be stopped at the Trident is true), and so it’s just cruisin’ for a bruisin’. A grey plague, with JonCon as the vector, could be bring more death than the Great Spring Sickness did back in the day. It could take out lots of characters too… minor, major, who knows. And I’m not guaranteeing anything, but will there be a person like Quenton Hightower, able to do what is needed for the long-term and for the safety of the many, rather than fall to short-term desires and the pleading of the few? Well, we’re just going to have to wait and see.
(BTW, someone once asked me if greyscale could be a defense against the Others, and um, how? It turns you to flaky stone, not adamantium. And then you die. Also before that you’re not invulnerable to being hacked to bits, I mean amputation is one of the attempted treatments for greyscale after all. Greyscale does not make you invulnerable to fire either, so nobody’s getting stoned to protect themselves from dragons tyvm. Also Targaryens are not immune to greyscale, so someone not getting sick is not proof of anything. Greyscale is not a solution to anything except life.)