The workaround is to reboot the PC (W10 latest). Anyone else seeing this? Solution?
I had this problem a while back with the Babyface Pro when changing the buffer size. Unplugging the Babyface and plugging it back in was an annoying work around, but certainly much better than a reboot. I see similar behavior if I change the buffer size during a Cubase session and don’t change it back after exiting Cubase. For example, if I pull up a youtube video or play an mp3, the sound is all messed up until I change it back to whatever it was before I opened Cubase. I fear I may have changed a setting in Cubase or the RME appplet, but I don’t have a clue.
Ok thanks - unplugging the usb and replugging would be ‘faster’ and less hassle. I keep watching for updates at RME to ‘fix it’. 
I have the original UCX, also on Win10 and C12, but I’ve never encountered such a problem.
You don’t have by any chance sonarworks systemwide installed? That program actually did make problems with Cubase, because it blocked changing the buffer size (but didnt have to reboot, closing that program helped)
Do let us know how it works out for you. By the way, I’m on Windows 11 (latest), Cubase 12 Pro (latest). Back when I was on Windows 10, I had the exact same issue as you, with total audio drop-out. Haven’t seen that on Windows 11, only what I described above. Something funky is going on between Cubase, Windows, and RME. My guess is it’s not RME. It’s been years without a driver update fixing this and I expect we’d have seen that from them by now if it is on their end. Just a guess. Have you reported it on the RME forums?
No Sonarworks here.