This is an idea I had while eating lunch and reading a Smithsonian magazine.
Imagine in the early 1340's ships from Europe reaching parts of North America and returning with evidence, including people. News and rumors of this new world spreads throughout Europe, more or less. More ships sail west and return, with people, animals, and plants. Then the historical Black Plague strikes on schedule. Those Europeans who survive put two and two together and decide that the Black Plague came from that new world across the Atlantic.
What does this do for further European attempts to sail west? How long till Europeans decide to take another look at the new world?
A big historical change is that Europeans (and others) know there is another land across the Atlantic. Hmm, would they think it is China/Cathey? If so, will the search for a sea route to China not be pursued?