Same happened to me and looking for the cause. Engine version is 4.21. Project settings were resetted to defaults when i opened the project. Blank entry map was opened and my game instance was not active.
I tought i hit a shortcut without knowing (my cats walking on keyboard makes too weird things) but cant find any shortcuts doing that.
Just copied config folder from one of my backups and its ok now. That happened to me twice. At first i tought i couldnt copied all files while moving to a new computer but second time, in the morning project settings were gone.
Always make versions of your projects. And your 3d models.