It took over 3 centuries to repopulate the area up to anywhere near the numbers that had been here.
One of humankind's most devastating plagues destroyed the Indian nations and cultures - not genocide!
In fact, just about the only folks to survive it had an European ancestor or two from the first contacts. They still suffer a very high infant mortality rate. Reference the Apostolic Charismatic Church of the First Born. They have their Indian roots although most people who come in contact with them believe them to be white. Still, the peyote use after main church services is one give away. Another is their practice of serial polygamy. There are others.
Those still identifying themselves as Indians, particularly those on the reservations, know about the infant mortality rate first hand, as well, and will tell you about it. I don't know if they do the same things as COTFB, but I wouldn't be surprised.