She was shown as being in the Iron Spider Suit (“Activate Instant Kill!”) which definitely still exists, since he left it at home, even with the OG Stark Suit destroyed. Also, was JARVIS destroyed every time an Iron Man Suit got destroyed?
In 2024, Peter Parker brought the Stark Spider-Man suit on his school trip to Europe. However, the suit was destroyed after Mysterio sent drones to blow up the bus containing Parker's luggage in London, thus eliminating Karen in the process.
I was under the impression that Karen was like every other AI, based at a 3rd party site and transmitting to wherever Peter was. Iron Man lost Friday when he went into space but got her back when he returned to Earth.
On the flip side, I don't recall her being in the Iron Spider Suit - Instant Kill wasn't necessarily a feature of Karen, just a feature of the suit that could be activated with a voice command.
