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Instead of a scenario where the original inhabitants of the Americas are immune to a disease what if there was an airborne virus that developed in the Americans that caused 8 in 10 to die. The virus just developed right around the time explorers arrive so there isn't any time for it to burn out in the Americas, and it's dormancy period is just long enough that it can be carried back to Europe.
What would be the effect on society if this virus spread throughout the old world?