Items in inventory in all modes, Creative, Survival and Adventure cannot be picked up by mouse by simply left-clicking, only by dragging by pressing the left button. Removing the items from hotbar in inventory of block selection cannot be done like the standard shortcut way in creative mode, ie. Shift -> Right - click  or by dragging them simply into the other blocks in the selection, rather only into the empty slots in any sections (Miscellaneous, Tools, Building blocks, etc.). Issue is still on in version 1.16.5, with Optifine and Forge or without them both, and in ANY minecraft worlds and servers.