“Biggest limitation is that WoW64 doesn’t work, so 32bit Windows software is still a no-op.”
OpenBSD finally gets Wine, and the Witcher 3 remaster runs on it. Years of work, credited to a handful of people, delivered as a patch to a mailing list with an “ok?” at the end. No 32-bit yet, and the advice is to run untrusted Windows binaries under a separate user. That is more security guidance than Windows gives you.