I don't know the exact cause, but here's what I have observed.

I have a physical steam link device that I use. I also play on my phone via the official app.

Right now 100% slay the spire 2. After this newest update, after playing on my phone, if I go the steam link and launch the same game, no controller input will be accepted. Often this also breaks the mobile app.

On mobile I use the game shortcuts to launch sts2. On the steam link I go into big picture and then launch the game.

The only way I have found to fix this is to restart steam. Annoyingly not something you can do through these remote devices.