Idk, it's still a physical place. I fully believe Precursors would be able to ignore this as they have no connections to physics or our concepts. I'm not sure about Flood or Forerunners though. The Halos were able to kill Keyminds, who infected and took control of reality (I couldn't say if they could infect the Hive realms). But their are a number of interpretations about the events in the books, so I can't say for sure.