Old World disease destroyed American Indian society in all respects. By 1648 even the least affected Indians, those living in what is now the Northeastern United States, were virtually exterminated by these diseases.
Oh, yes, the Iroquois won their 300 year war with the Mohicans that year ~ the next they adopted the remnant of a few hundred members into the Oneida tribe. They still exist in the Munsee Band up on Lake Winnebago.
From that year on America belonged to the Europeans, and the Indians who were left went to work as professional meat hunters and guides.
A recemt article in Scientific American concerning the possibility of a new Ice Age points to the atmospheric CO2 drop that may be directly attributed to the sudden absence of over 50 million American Indians raising crops.
BTW, I have seen several figures on the estimated number of Natives in NA at the arrival of the Europeans, but have not seen one as high as 50 million. Do you have a link to a source for that?