Mutations and Malaise / Curse
I will explain malaise so the effect of some mutations is more clear since you don’t need those mutations as often on lower BC than on higher BC.
Mutations can be picked up after each biome so that the player has 3 before the first boss. This is also the maximum number of mutations one can have. Mutations can be reset for gold.
In higher difficulties damage comes from scaling (same as normal) but mutations are used mostly as a “safety net” or more survivability which might differ from what you are normally using. Mutations scale with the stat they are assigned to (if they have one) for example if you have high survival your healing from necromancy will also get higher the more survival you get. No matter what build you can pick what you want for example necromancy gets picked in a lot of builds in high BC even if one does not run survival.
Again I have more experience with some mutations than with others please understand that my opinion might be (it is safe to say that it is) flawed.
So malaise isn’t only lore-wise in the game. It is a very interesting mechanic in the game that affects gameplay but it mostly only is a problem in higher BC.
What can give you malaise?
On anything lower than 4 BC only the elites in high peak castle that drop a key to the throne room can give you malaise. They give you two bars instead of one.
In 4 BC any enemy can give you 1 bar when you get hit. Blocking a hit with a shield doesn’t make you take malaise from that hit. A normal malaise bar can fit up to 10 little bars/parts. When the whole bar (10 little bars/parts) is full your maximum health goes to 10% of what your max health can be without the malaise (your healthpool if you are 100% full). Then anything will kill you instantly as you probably guessed or are familiar with. Below I will explain all the mutations but I hope this clears up how this works and how some mutations might affect this process.
When breaking a golden door (with gear) instead of paying or opening a cursed chest gets you cursed (10 for cursed chest). You need to kill enemies without taking damage to lift the curse. (Any damage will instantly kill you, no mutation can avoid this not even “the Yoli”) Damage from darkness in the forgotten sepulchre does not kill a cursed player but poison/spikes and anything else does. Mutations can help this process but not entirely get rid of it. The new rune in 1.5 is really helpful since you can see the amount of enemies left (but don’t forget the doors which can have enemies)
One Hit Dead Mechanic
If you are above 25% health and you take a hit that would normally kill you, it won’t.
You will stay on 1 hp and all the enemies will be stunned for 1 second. This is the one hit dead mechanic. (Can be disabled in custom btw).