I can run the 6.22 portable version but my install of Calibre stopped working. I thought I will fix this by updating to 6.22, but it still is exactly the same.
The app starts, the splash logo appears in the middle of the screen and then there's nothing but the app tile on the taskbar (below)
https://i.imgur.com/Rke8utW.jpg
and the process in taskmanager (below)
https://i.imgur.com/s0TXPIW.jpg
EDIT: not sure why images are not loading. Added direct links