When running PANDA using the -icount option, with any shift value whatsoever, I get the emulator eventually terminating with the message "Raised interrupt while not in I/O function" while working with 64-bit Windows images (Windows 7 and 10). This behavior does not arise with the version of QEMU that I have on hand (version 4.2.1).

I tracked this down to the following in translate-common.c, beginning at line 48 [1].

        if (!cpu->can_do_io
            && (mask & ~old_mask) != 0) {
            cpu_abort(cpu, "Raised interrupt while not in I/O function");
        }

Rather than go to the trouble of modifying PANDA's source and rebuilding on an isolated machine, I just found the code in libpanda-x86_64.so corresponding to the offending lines and nopped it out. The patched result runs reliably so far.

[1]