The Europeans had endured some of the most devastating diseases that arose do to them choosing to live in close quarters with animals. The Americans just didn't have this habit. A lot of terrible diseases come from something that jumped species.

Syphilis may have originated in the Americas.

The Old World was a much larger "disease production lab", especially zoonotic one, where a disease jumps from an animal to a human. This transmission happens especially often between domesticated animals and people who are in everyday contact with them.

The New World people only domesticated a handful of animals, such as the guinea pig and the llama. So, fewer opportunities to catch something from them.

Still, they had a new disease that spread to the Old World: syphilis, which certainly killed several million Old-Worlders, only it took longer to run its course and could be prevented by, well, chastity.

An interesting idea: if you count victims of smoking towards the total death toll (tobacco is a New World plant), it may well be that the Old World suffered more deaths from the Columbian Exchange. But spread over a much larger population and a much longer time, these deaths didn't amount to destruction of entire civilizations.

Many of the most deadly pathogens to indigenous Americans were born from livestock or frequent cross-exposure between different populations spanning Europe and Asia.

See https://en.wikipedia.org/wiki/Native_American_disease_and_ep...