Shegnada’s recommendation to go slowly and consider all the unforeseen effects as they come up may be the best approach for a lot of projects.
But as far as the technical question, can you edit the spellingstatus.xml file outside of Paratext and preserve your spelling status while applying orthography changes, I think it should be possible. Although when I was experimenting, I did come up frequently with the “spelling status is corrupt and has been removed” message. But if I applied the changes to the spelling status and to the book files at the same time, then started Paratext and brought up the wordlist, it worked. So I think what makes Paratext detect corruption in SpellingStatus.xml is significant mismatches between that file and the words it finds in the text.
Similarly, I could change the spelling of words and morphemes in the lexicon.xml file and also in the different interlinear xml files (one per book, in the folder named for the glossing language).
Similarly, one can change the renderings in the BiblicalTerms.xml file.
One challenge would be if the orthography changes would apply to the English words or bits of words inside XML files, you would have to develop a process not to modify those words.
For instance, a bit of SpellingStatus.xml looks like this:
<?xml version="1.0" encoding="utf-8"?>
na terniawꞌekepna
Any rule that could apply to “SpellingStatus” or “Status Word” or “State” or “encoding” , etc. would have to be constrained so it is only applied to the language text within the quote marks.