Try giving calibre a dedicated location for its temporary files via the CALIBRE_TEMP_DIR environment variable, see
Calibre User Manual - Environment variables
Which version of Win 10. In 1709 there's a new feature, "Controlled Folder Access", that 'stops' programs using some folder operations - like opening them! Its a means of thwarting ransomware attacks. Might be worth checking out if its enabled. I think you have to opt-in to make use of it, and I have NOT heard of it deleting anything.
However there are 3rd party tools that attempt to do 'garbage collection' of the Temp directory, wouldn't surprise me if an AV vendor or something similar added such a feature - which you have to opt-out of Ψ²
BR