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Runtime HMI / PC with InteractX Deployment Server running can block a com port from being used IF the runtime download method selected in the Deployment Server is set to look for "Serial" downloads.
Since the Deployment Server constantly looks for attempts to download updates, the Com port that you pick to do downloads is constantly monitored for a download attempt. This keeps the InteractX COMM Server from using it since Serial ports can not share access like the Ethernet port.
Most units are set to NET for network downloads or NONE if using the USB disk transfer method of updating runtime files.
If you update a unit via USB, it overrides the checked option in the Deployment server and releases the Com port until the unit is rebooted. So, after the USB update, you can run InteractX and there will not be any error since the com port has been freed. On rebooting, the error related to the Com port will show up.
The fix is to only check the serial option if you need to do a serial download for some reason then reset the setting to NONE when the update is complete. The Deployment server icon is in the Windows Desktop System tray.