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.

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.

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...

Syphilis may have originated in the Americas.