>Europeans didn't really get to most of the more isolated inland areas in the Americas until the 1600s or well after that, though.

It takes more than a few decades for things to regrow. There's a reason that half of all towns in New England have the name "field" in them. The impenetrable thicket that characterizes unmaintained New England land would have been foreign to literally every human to ever set foot there prior to the mid 1700s (decades of re-growth after the natives had been mostly driven off but not long enough for complete cultivation by europeans).

Now, obviously that's not that far inland, but by the time you're talking about the french surveying the continental interior native populations had stabilized. The worst disease epidemics were very much at 1500s and early 1600s thing.