The idea that there was open space in the Americas before the Europeans came is a myth. It neglects the inconvenient fact that the native Americans were already here.
The indigenous population of the Americas was absolutely destroyed by Old World diseases. This happened mostly by accident (although sometimes done intentionally) but was probably near inevitable once first contact was made. (In many places it out-paced the actual extent of direct European contact as indigenous people traveled.)
So there WAS vast expanses available by that time, even without intentional genocide (which also happened).
Disease killed a lot of the native population, maybe even decimated, but it did not leave the USA a vast open space. Otherwise the US Army would not have had almost continuous warfare from the conclusion of the Revolution War to the surrender of Geronimo (minus the Civil War) to displace the natives to make room for American settlers.
https://en.wikipedia.org/wiki/United_States_military_casualt...
A large percentage of the land battles of the War of 1812 were fought between the US and natives because the US wanted the land of the natives to become open space so the natives allied themselves with Britain.
Lewis and Clark would not have survived or even made it to the coast if they had not had help from most of the tribes they met along the way. Of course we displaced all of the natives they met eventually.
So why settlers spent so many bullets to kill people who were already dying by nobody else's fault? And if there was so much open space in America, why Europeans happened to locate exactly in the "very few" places where natives lived? Strange, indeed.
In the specific year you state was four years before Lewis and Clark started their expedition. They would not have survived if they did not have help from most of the natives they met along the way, one of the main objectives was to document all the natives that lived there. That would have been kind of weird goal if it was all open space.
re point one
the __lowest__ plausible percentage of North America and South Americans that died of disease before ever hearing a rumor of it source is 90% and has a fair chance of being higher, the disease front traveled as quickly as the natives, refuges from one dying village to the next, or people coming to investigate why no body has visited from the next community over in a while.
The deliberate atrocities later were just a mop up action in the larger picture.
I've read estimates of smallpox outbreak at 20-50% mortality across the continent. Some areas in New England are estimated to have a 96% mortality rate. Pretty crazy.