I know that it was sometimes (not sure how often) intentionally spread for ethnic cleansing purposes, and that the colonists and explorers were systemically brutal and terrible to the natives.

But if these people were naturally susceptible to catching European diseases due to lack of exposure in the Americas and they naturally spread like wildfire and decimated the population, wouldn't something like that have been inevitable (assuming technology would lead globalization and cross-continent communication to happen at some point)?

I'm sure the Europeans could have washed their hands and coughed into their elbows more, but was something like that actually feasible at the time? Or was there no way the native population could have survived?