OK, just an update - turns out the initial problem was caused by a new feature of the Sophos Home Beat AV I am trialing.
For those interested, through process of elimination I identified that it was "Configure - Advanced - Risk Reduction - Prevent DLLs loading from untrusted folders". Once this was turned off, all was good again. As I prefer to leave as much turned on, under "Configure - Antivirus - File and folder exceptions" I added the Calibre Library location, the AppData\Roaming\calibre\ location and the Calibre install location. Once these were added I turned on the Risk reduction setting again and all worked as expected.
Thanks everyone for all your help, and once again great app
