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Also the wild tea item removes a bad quirk but has a small chance to remove a good one. Locking in also protects it from that :O
You can only lock in one positive quirk per character.
Being locked in means it cannot be replaced when new positive quirks are added to the character. You can only hold a maximum of 3 positive and 3 negative quirks at a time, so if a new one is added when you're at the limit, one of them gets replaced.
It depends how aggressively you're approaching progression. I won the 1st Confession, wiped on the 2nd Confession's final boss, then went back to the 1st Confession and won it three times with few character deaths. So far, my characters were more likely to live than die. And I play on default difficulty, with the easy mode Flame someone might find that their characters survive almost every time.
But admittedly the cost of locking a Quirk in is very high and it definitely hasn't been worth doing for me yet.