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Useless here.
That's your best option. At least the cleanest one.
If you got some Steam achievements today and lost the corresponding in-game secrets, you could press alt+F2 in the stats menu. This forces the game to read your Steam achievements and unlock in-game secrets accordingly.
However, expect visual inconsistencies: corresponding completion marks will not appear, and completed challenges will not be crossed out.
It's a bit of a mess, but since secrets are unlocked, stuff can be generated during runs.
Note:
The most common origin of the "can't save data" issue are paranoid antivirus programs. Might want to add Isaac to your antivirus whitelist, so it doesn't interfere anymore, just in case.
"But it never did that before" is irrelevant. Updates happen, they can go crazy at any moment.