Well, no NPC’s whatsoever I see being unlikely.
During an interview after E3 with Todd Howard, Craig Lafferty and Jeff Gardiner, it was discussed that the experience would be familiar, but the main difference being that the “other players aren’t NPC’s, they’re real people”.
Howard goes on to explain how there are still plenty of robots, more so than before, that will lead the story lines. There will also be the existing enemies from Fallout 4, and additionally new monsters, notably Mothman.
Mothman is a creature reportedly seen in the Point Pleasant, West Virginia, area from November 12, 1966, to December 15, 1967.
The first newspaper report was published in the Point Pleasant Register dated November 16, 1966, titled “Couples See Man-Sized Bird … Creature … Something”
Nonetheless, you can expect to see a whole host of scary new monsters.