sys-usb works with one device (my yubikey). After booting, i get a shell in sys-usb, do lsusb and all is good. Then i plug in a second USB device (a usb mouse), and then I found this chunk in dmesg (pasted below). It’s not obvious if its recommending adding irqpoll to the xen grub /etc/defaults/grub or if its recommending adding irqpoll to the usb-sys boot procedure.
[ 680.028708] irq 44: nobody cared (try booting with the "irqpoll" option)
[ 680.028800] CPU: 0 PID: 0 Comm: swapper/0 Tainted: G O 5.4.98-1.fc25.qubes.x86_64 #1
[ 680.028872] Hardware name: Xen HVM domU, BIOS 4.8.5-30.fc25 02/18/2021
[ 680.028913] Call Trace:
[ 680.028933] <IRQ>
[ 680.028954] dump_stack+0x66/0x81
[ 680.028981] __report_bad_irq+0x30/0xc0
[ 680.029007] note_interrupt+0x232/0x270
[ 680.029032] handle_irq_event_percpu+0x51/0x70
[ 680.029062] handle_irq_event+0x36/0x60
[ 680.029086] handle_fasteoi_irq+0x83/0x130
[ 680.029111] generic_handle_irq+0x24/0x30
[ 680.029136] __evtchn_fifo_handle_events+0x14c/0x1b0
[ 680.029169] __xen_evtchn_do_upcall+0x70/0xd0
[ 680.029199] xen_evtchn_do_upcall+0x27/0x40
[ 680.029225] xen_hvm_callback_vector+0xf/0x20
[ 680.029254] </IRQ>
[ 680.029271] RIP: 0010:native_safe_halt+0xe/0x10
[ 680.029302] Code: ff eb bc 90 90 90 90 90 90 90 90 90 e9 07 00 00 00 0f 00 2d 86 8d 5e 00 f4 c3 66 90 e9 07 00 00 00 0f 00 2d 76 8d 5e 00 fb f4 <c3> 90 0f 1f 44 00 00 41 55 41 54 55 53 e8 30 f1 73 ff 65 8b 2d b9
[ 680.029400] RSP: 0018:ffffffff8d603e78 EFLAGS: 00000246 ORIG_RAX: ffffffffffffff0c
[ 680.029443] RAX: ffffffff8ca1fc90 RBX: 0000000000000000 RCX: 7fffff61bbbe9658
[ 680.029484] RDX: 0000000000000000 RSI: 0000000000000000 RDI: ffff911b10c1c500
[ 680.029526] RBP: 0000000000000000 R08: 000000002c5b3698 R09: 000000000000031a
[ 680.029568] R10: ffff9daac02c3d88 R11: ffffffff8d65a000 R12: ffffffff8d614780
[ 680.029609] R13: ffffffff8d614780 R14: 0000000000000000 R15: 0000000000000000
[ 680.029652] ? __cpuidle_text_start+0x8/0x8
[ 680.029678] default_idle+0x1c/0x140
[ 680.029703] do_idle+0x1bd/0x270
[ 680.029733] cpu_startup_entry+0x19/0x20
[ 680.029761] start_kernel+0x7d7/0x819
[ 680.029787] secondary_startup_64+0xb6/0xc0
[ 680.029811] handlers:
[ 680.029830] [<00000000ff979979>] usb_hcd_irq
[ 680.029875] Disabling IRQ #44