I am 90 hours in and unlocked The Lost (though I only learned about it through spoilers).
Doing Lost runs is absurd. I understand that this is hardmode-cum-hardmode but come on.
Imagine your first time running through with ??? who didn't have red hearts, but at least ??? can pick up soul hearts, eternal hearts, and even get red hearts with +hp pickups.
The Lost can't get any kind of health pick ups at all, all hits are 1-hit-dead (unless you have something like the Holy Shield, which negates first damage, or something like the Infamous mask). So not only do you have 0 margin for error but probably half the items in the game are completely useless to you (anything that gives health, or reduces damage, or has an effect on taking damage).
I am more than 200 deaths in and have killed Mom maybe twice, but both those runs died during the boss rush room - let alone whether I could survive It Lives (who is, in my opinion and depending on the damage potential for the run, harder than Isaac, ??? or the Lamb).
It is incredibly frustrating and I'm this close to just giving up on getting Platinum God, because you have to kill everything short of megasatan on hard mode with him to 100% the achievements. Fuck that.
IMO it should maybe have some health (maybe starting with just a half container), but always be hidden, and all +hp/soul/evil pick ups provide only a half heart container rather than full one. Or have only eternal hearts provide a half heart container. Just... something to give you a greater margin of error that isn't one single item.