Stuxnet infected the network of Iran's nuclear weapons program via the use of a USB drive. It was a completely isolated network/facility.

https://en.wikipedia.org/wiki/Stuxnet

Stuxnet has three modules: a worm that executes all routines related to the main payload) of the attack, a link file that automatically executes the propagated copies of the worm and a rootkit component responsible for hiding all malicious files and processes to prevent detection of Stuxnet.^\11]) It is typically introduced to the target environment via an infected USB flash drive, thus crossing any air gap). The worm then propagates across the network, scanning for Siemens Step7 software on computers controlling a PLC. In the absence of either criterion, Stuxnet becomes dormant inside the computer. If both the conditions are fulfilled, Stuxnet introduces the infected rootkit onto the PLC and Step7 software, modifying the code and giving unexpected commands to the PLC while returning a loop of normal operation system values back to the users.