I'm seeing this as well on my mother's iMac with an external touchpad. I see this problem even when I'm attached to the computer remotely using RemotePC. What fixes it for me is right clicking on an application in the Dock and then right clicking on Quit. That seems to reset the mouse somehow and the left click starts working again. My mother has called me two days in a row so this problem seems systemic. I see that others have had success with external mice so I may try that.

Just had it happened again to my mother's computer. The right click did not work this time but option-clicking on on of the applications foregrounded it and cleared the issue. So some click+keyboard combination which switches applications either by foregrounding or quitting seems to clear the issue.