I called in this issue with the Apple helpdesk. She had me log in to safe mode, then reboot. Since then the issue hasn't reocurred. So try this!

Same problem here, Macbook pro 16 inch. Updated to Big Sur a couple of weeks back and now, sometimes when I wake my Macbook from sleep, the primary click isnt doing anything. Not from the trackpad neither from an external mouse, either connected via usb or via bluetooth. Seems like something that should be fixed on the double.