Currently it uses a tiny preview file smaller than a thumb, which due to how the engine scans files means it will probably never return results. Using the full file or even the sample instead should be all you need to do to fix it.

I always thought reverse image searching downscaled the image anyway and this wouldn't cause any problems, but if that's not the case +1 to this.

Yeah, I reported this issue a while back.

I presume that it's done this way because of restrictions on filesize and image dimensions. Based on my research, they are as follows:

Google       20MB      8000 x 6000
SauceNAO     15MB      ???
Derpibooru   20MB      ???
Kheina       8MB       7500 x 7500

Instead of dynamically selecting the appropriate file, e621 just falls back on the thumbnail, which will always fit those restrictions. But yes, it will definitely cause false negatives.
post #2304693 is a good example of that. Searching Derpy by the thumbnail will produce no results. Searching for the sample will actually produce the appropriate image.

But yes, should probably be a pretty easy fix. +1 from me.