Sample size of 1, but I ran an RPi4 just fine on a USB thumb drive for about a year.

Still upgraded to an SSD later because I wanted even more storage space (and SSD seemed to have better random IOPS than a thumb-drive), but I'd say go for it.

I don't really know. I assume they would be slower than SSDs though, but I have never measured USB flash. The SSBs get some 300MB/sec on my Pi 4 boards.