I don’t think that can be concluded, the Spanish appear to have made little to no contact with natives during those early exploratory ventures that weren’t real

I don’t think that can be concluded, the Spanish appear to have made little to no contact with natives during those early exploratory ventures that weren’t really expeditions in that sense, but rather more scouting. So, e.g., they described being on large bluffs overlooking the horizon and setting an immense number of smoke columns rising, as would be expected from tribal communities, which were then not at all witnessed 100 years later. I also don’t think it’s conclusive that it was disease or disease alone, it’s the rather blind assumption today that it must have been disease and somehow that makes Europeans culpable for something they also didn’t understand, but there are any number of things that could have happened in 100 years that led to such changes. It seems more plausible to assume that semi-nomadic hunter gatherer societies that were extremely conflict prone would have likely moved, been overrun by hostile tribes and/or been decimated in wars with other tribes, faced hunger, followed livestock, or simply just moved. In spite of the semi-religious nature of what I’ll call native-worship, (and don’t get me wrong, I find them fascinating for different reasons) fact of the matter is that the indigenous people were very underdeveloped relative to the European state, and as such were confronted with all the similar trappings of hunter-gatherer societies that didn’t even have the wheel, let alone a writing system or even bronze weapons. They were in effect Stone Age people, dealing with Stone Age systems and parameters. And that doesn’t even go into the fact that genetic testing has shown that the mass extinction event of the Americas due to what were Asian pathogens that Europeans almost didn’t survive either, was inevitable because any contact prior to the technology of the last few decades would have resulted in the same outcome.