Hello, I’ve encountered this bug while setting a widget interaction in the center of the screen of the third person character and a simple actor that has a button in the widget.
I can execute a button click only the first time with the mouse click, then it only triggers with Enter or Space buttons. It also disables character movement and once I click elsewhere where there is no widgets, I gain back the character controls.
In 5.0 this works without any problems. I’ve tried to disable Enhanced Input in 5.1 from the project settings but it didn’t work too.
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Are you using the “Set Input Mode UI” node without executing “Set Input Mode Game” later? Some screenshots of relevant event graphs would help. 
I’m on a new Third Person Template project
The “Set Input Mode UI” makes the widget only interacts with the “Cursor” where in my case it should be the “Widget Interaction Component” that I’ve set in the Third Person Character and its Interaction Source is the “Center Screen” value.
This works perfectly in UE 5.0
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You should report this as a bug and/or post it to the “Feedback For Unreal Engine” category.
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I can reproduce this issue aswell
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I found out that this bug has been reported couple of months ago here World Widget Interaction Problem with buttons in Unreal engine 5.1
