Dual-Monitor setup.
When you switch to the 2nd screen (either by tabbing or simply moving the cursor in that screen and clicking something outside Hearthstone) and then switch back to HS, the Overwolf overlay is activated and the cursor is set to the overwolf cursor. You can’t interact with anything in the game at all.
The only way to fix it is to move the cursor to the other screen, click anywhere there and then click anywhere back in HS. That fixes it until you switch back to the 2nd screen, which means every 5 seconds.
Update
This occurs only when as you drag your cursor to the 2nd screen, you hover over a card in the overlay on the way. If you don’t touch the firestone overlay at all as you move the cursor to the 2nd screen, the issue doesn’t happen.
Also the issue only happens while inside a game when the firestone overlay is active.