Cahokia, according to BBC, was a Native American city near present day St. Louis. It reached its peak of about 30,000 people around 1,000 A.D., which may not sound impressive but was a larger city than Paris at the time. One interesting thing the article mentions is that there is no evidence of a market economy found, but instead the city appears to have been a “cultural center” renowned for feasts, parties, and…graveyards.
This is a seminal 1976 paper by Alfred Crosby on the epidemics that devastated Native Americans after Europeans first came. I’m sure there is plenty of scholarly work since then that may have refined this, but it is horrifying even if some of the details have changed. The most extreme estimates are that as many as 100 million people lived in the Americas pre-Columbus, or one-sixth of all humans alive at the time, and only a few million survived. If true, this is much worse than the Black Death in Europe. This would mean that Native American civilizations might have been equivalent in size and sophistication to European and Asian ones. We just don’t know.
I think this is also a cautionary tale for what a novel disease or combination of novel diseases could do to our current civilization, whether natural or man-made. He does point out though that genetic factors and never having been exposed before were only some of the factors. People at the time did not understand quarantine for example, and some practices for dealing with the dead led to more contagion. People might have been weakened by exotic diseases like smallpox, then finished off by diseases they would have experience with like malaria or pneumonia. They didn’t understand how hydration, nutrition, and keeping warm could keep their strength up to fight off secondary infections, or else people may have been too sick to fetch water and food and keep fires burning. Hopefully we can do much better today if and when some terrible epidemic strikes.