Actually, the OS does not run on the USB drive. The OS runs in RAM. It is unpacked fresh at each boot from the archives on the USB drive into RAM, and all of the usual OS files are actually read and written to RAM.
After boot, some settings that you have made in the webUI are also read from the USB drive into RAM. And of course, if you make any settings in the webUI, these are written to the USB drive so they can be read on the next boot. Other than that, the USB drive is accessed very little.
You can always download a backup of your USB drive by going to Main - Boot Device - Flash and pressing the Flash backup button.