It's possible, but hard to say for sure. Opus won't do anything different whether in the root or lower down, and things should work as long as the drive/filesystem respond to the standard APIs as appropriate.
A Process Monitor log of what happens when no results are returned might shed some light on it:
Filenames starting with ~ and containing .tmp may complicate things, as they tend to be temp-files involved with Office doing "safe saves" and are treated specially in some places. But not all of the names are like that, so that detail may not be important.