I just solved this problem for myself again. I've had this problem before, solved it, and forgotten the solution.
For me it was Spotify which hijacked my media keys. Spotify didn't respond correctly, and I'm using multiple desktops, so I didn't know it was running. Once I opened it, I saw it was responding to media keys (play/pause), and once I exited it, YouTube in Chrome began responding again.
I'd like to say a big f*** off to Spotify for this behavior, and Microsoft also for just generally being so difficult to troubleshoot after all these decades.
Maybe get out of the vaccine and GM mosquito business and focus on a better UI/UX for the world's leading OS (and yes, I know that's Billy G and his foundation, not Microsoft technically, but it's all the same damned big business club. Don't get me started on Google/YouTube. "Don't be evil" my ****. Oh, it auto-blanked out a-r-s-e. Wow, how PC).