AFAIK Nix wouldn't solve this as it has the same issue (/nix/var/nix/db). Here's a scenario to better illustrate:

I'm using systemd nspawn with my host root as a lowerdir overlay. In this container I install some packages not present on the host. The overlay upperdir now includes the new packages and the new package database. I upgrade my host, and now the nspawn package database is wildly out of date because overlay doesn't track line-level file changes.

OverlayFS is really handy but it causes a ton of churn from rebuilding everything.