I suppose you're asking about the modern-day US, but in case you're interested in other regions I wrote about this for Aztecs of central Mexico.
From the sources I know there are short reports of the disastrous effects of the epidemies of the mid- to late 16th century, but no attempts at explanation that I'm aware of.
Some additions for your question:
At this early point in time (16th c.), Spaniards would not have necessarily made the connection either of them bringing over disease - and certainly not from our modern understanding of immunology (ie. of native Americans lacking immunity to diseases like smallpox).
Rather we find a multitude of explanations: tying the epidemics to everything from the American food to climate, to a punishment by (the Christian) God. Esp. the latter one was popular as one more of placing native people in an inferior social position. The reasoning of Europeans went that indigenous people as non-Christians were receiving the "wrath of God" due to their wrong faith [note: I'm only relating and in no way condoning those views].
The other caveat for my above answer is that most of the important writing by Mexican native writers deal much more with pre-Hispanic times, which was less risky to discuss than their own time. Those passages I do mention are by authors living in the 17th c., and so less familiar with those earlier epidemics. Plus the many native colonial maps we have do not really work as sources for your question either, lacking more text.
Still, I find that the excerpts I mention above do give a sense of the immense loss people and culture then still very much happening throughout central Mexico. We're talking of over 90% population loss in modern-day Mexico into the 17th c., of a region with roughly 20 million inhabitants in pre-Hispanic times - through epidemics, combined with the effects of wars, forced labor and often harsh working conditions.
Finally something that I can answer. Albeit, with a Canadian example but if you consider the word American to mean North American, then it works.
In 2018 the Government of Canada officially apologized and exonerated six Tsilhqot'in chiefs that were hanged in the mid 1860s. In the apology, the federal government echoed the wording of the British Columbian provincial government's exoneration in 2014 that the historical record reliably showed that the chiefs were unjustly executed. Both governments now believe that the Tsilhqot'in who attacked and killed 21 road workers in 1864, were doing so under the orders of the chiefs to protect the sovereignty of their territory.
During the early 1860s the colonial government in the territory of British Columbia was aggressively attempting to link the capital of Victoria with the gold fields of the Cariboo Gold Rush and ultimately the British colonies in the east. The colonial administration believed that the Bentinck Arm --a long inlet jutting into the mid-coast of British Columbia -- would be where the sea would meet an overland route and the Bentinck Arm Company sought to claim the land in the Bella Coola valley. Official colonial policy was that land could be claimed as long as it was uninhabited. George Cary was the Attorney General for the colony and noted in a letter that there were "no Indian settlements" in the Bella Coola valley. This is the traditional territory of the Nuxalk population and was well-documented to be well-populated as the site is strategically important and adjacent to abundant fishing grounds. The land would be extremely valuable if a road was pushed into the interior of the country.
Small pox would have been well-understood in the 1860s by the English. Inoculation via cow pox would have been a widespread practice dating back into the previous century and English Law also criminalized the spread of small pox. A smallpox outbreak in Victoria in 1862 led to many people being vaccinated and quarantined to stop the spread. Many Indigenous people were located in and around Victoria at that time were infected and quarantined with no access to medical care. Other Indigenous people were forcibly removed from Victoria and sent back to their own territory often at the barrel of a gun.
At the same time colonial settlers are pushing their way into Tsilhqot'in territory. One, Francis Poole, was actively transporting individuals infected with smallpox and leaving them in different communities as he made his way up the Bentinck Arm. Travelling with infected who were not quarantined would have been known to spread the disease and actually illegal under English Law. Poole himself in his memoir writes that his exploits into Tsilhqot'in territory "left behind a sorrowful trail of blood.”
The actions of the Tsilhqot'in chiefs and warriors who killed 21 white settlers, are best explained by an attempt to prevent smallpox from further entering their lands.