Still having this issue? I've had (I think) the same problem since Big Sur, too. Left-click, only, quits working. I can right-click and move the pointer. Just can't click. Happens once to twice every day or two. I have to use the keyboard to reboot to correct it. I've reset PRAM and SMC and booted into and back out of Safe mode. No difference. So, this is what I've done and am doing next, partly due to conversation with Apple. First, I noticed via Activity Monitor that a couple apps weren't behaving well under Big Sur. Tenor GIF keyboard was using 10% CPU while doing nothing. Webex Teams was not allowing my Mac to sleep. Stopped both of those from loading automatically. If it happens again, I'm going to stay in Safe mode for an extended period to see if it happens. Recommend keeping an eye on Activity Monitor to see if anything seems unusual. I'll report back with results.