It sounds like your keyboard isn't either sending the correct
keycodes or they're being intercepted by the desktop shell.
You can verify that your key presses mean what you press by
running xev in a terminal. Here's me pressing left ctrl + left alt
on my happy hacker keyboard (PC).
KeyPress event, serial 36, synthetic NO, window 0x4a00001,
root 0xbe, subw 0x0, time 675936933, (432,537), root:(2033,590),
state 0x0, keycode 37 (keysym 0xffe3, Control_L), same_screen YES,
XLookupString gives 0 bytes:
XmbLookupString gives 0 bytes:
XFilterEvent returns: False
KeyPress event, serial 36, synthetic NO, window 0x4a00001,
root 0xbe, subw 0x0, time 675937205, (432,537), root:(2033,590),
state 0x4, keycode 64 (keysym 0xffe9, Alt_L), same_screen YES,
XLookupString gives 0 bytes:
XmbLookupString gives 0 bytes:
XFilterEvent returns: False
You can change the key combo that locks the screen, it's under
System Settings->Keyboard->Shortcuts->Lock Screen. You could completely
disable it if you want.
QEMU/KVM, which is what's actually managing the VM, appears to
have several options for setting focus grabbing defaults.
‘-alt-grab’
Use Ctrl-Alt-Shift to grab mouse (instead of Ctrl-Alt).
‘-ctrl-grab’
Use Right-Ctrl to grab mouse (instead of Ctrl-Alt).
Now I'm not sure how you would tell virt-manager to keep this
default but it is easy enough to grab the arguments it's using the
run your VM, run it yourself from the CLI, and just add one of these
switches to see if it addresses your problem. If it works, then write
a simple script to start your VMs that way. Easiest thing to do is
disable the screen lock shortcut and just use the gui to accomplish
that. Good Luck.