We do know from the records of the first English colonists that the Americas resembled a vast abandoned park. Millions of acres of forest had been burned to create grasslands and there was evidence of a lot denser population in the past. We know too that in the lower portion of N America and in Central/South America there were cities whos size rivalled or surpassed any city in Europe.

It seems that the aboriginals of the Americas were ill equipped to deal with foreign diseases. Remember that Europeans had a much more diverse ethnic population and had contact with Africa, Asia and Asia Minor. Even so plagues of the day killed half their population. The native Americans suffered far worse mortality once their "virginal" immune systems were faced with new bacteria.