Oof yeah, Shadow DOM and accessibility can be tough.
The main thing to be mindful of is that so much of ARIA is based on ID references, so you have to be really careful to make sure your labels and whatnot are inside the same scope. I showed off a workaround I use sometimes in this video (https://www.youtube.com/watch?v=rr3c62Wnaeo). We're hoping to make this better with AOM (https://github.com/WICG/aom) because it will let you label things with an element reference, instead of a string ID.
If I recall, I believe Shadow DOM does reset the scoping for tabindex. So if you have something that's tabindex=10 inside a shadow root, it will be first in the tab order once focus moves into that shadow scope. But it won't be first in the tab order for the entire page.