I have tested sys-net, sys-firewall and sys-whonix. No difference.
Also tested StandaloneVM based on Fedora26, Debian9 and Windows7. No differences.
I've been able to connect a Nano S, via a sys-usb, to an appvm based on fedora 26. A couple things to look out for:
When you switch into or out of apps on the Nano (and maybe when you enter your PIN, I don't recall), it will be detached from the appvm. So you'll find yourself often re-attaching the Nano. Use `qvm-usb` on dom0 to check whether it is still attached to appvm.
Ledger's software gets flakey when you're running more than one of it's apps or browser plugins. Make sure you don't have bitcoin wallet (or any others) open while the Ledger Manager app is open.
Hope that helps, -Dave