Poked around on other forums, mentioning the X86-S spec, and folks there pointed out some VirtualBox tidbits:
- old versions of VirtualBox emulated enough of a CPU such that they could run OS/2 when other virtualization products couldn't.
- newer versions of VirtualBox no longer needed that emulation layer, as they could pass things thru to the CPU directly. But, to this day, VirtualBox still has pieces of QEMU in it.
Most likely, both VirtualBox and QEMU will be able to run OS/2 long after a particular x64-only CPU can't. I'd guess that Intel needs a new line of x64-only CPU's to carry them further into the server ecosystem. But I'd also guess that they'll continue CPU's that support legacy business apps for a long time (lots of money there).
If DOS, an OS that is older than OS/2, can be emulated and survive & thrive to this day, there shouldn't be any reason why OS/2 (all variants) can't be emulated as well, and prosper long into an x64 world. VirtualBox (virtualization) and QEMU (emulation) will get us there.
CPU's might take away a needed "layer of compatibility" on the one hand, but they almost always give back with "speed" on the other hand. Emulation developers do the rest ...