I literally can't click anything after tabbing out or opening certain app overlays. I'm pretty sure Discord breaks it, although Steam Overlay works.
Right clicking also works, but obviously, that's not good enough.
My fix for it is deleting %appdata%/SpaceEngineers/ColdStart.txt, but that gets annoying *really* quickly.

The couple times I had a game crash, I couldn't even left click to confirm sending the crash report.