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You will want to grab the photo with him and keep his max health low for the shield. Combined with a Dark Bum and you have a good chance of keeping him "mostly" alive.
There are some rooms you are honestly just going to take a lot of hits or wipe on, there's not much you can do there.
- Are you going down the main path?
- Are you using Devil Deals?
If both are yes, then stop that, that's making your life harder. I strongly suggest snagging both items in the alt path item rooms and doing the same with angel deals.
Bring them into co-op with a character you want to use. Let them die.
Somehow they still get clear marks while dead. Not sure if this got fixed in the recent update though. Partly because I’m not doing this myself.
FYI, line up the characters and make them take both items. There are some item layouts that make it hard, but the speed stat is shared, so it can't be that hard to arrange them to pick up both items.
In all reality, Jacob and Esau are just characters with a bad mechanic for a game like this, in which precise movement is essential to playing well. Getting a good run as Jacob and Esau is heavily dependent upon getting good items, the majority of which I personally invest into Jacob. Like others have said, taking the alternate paths allows you to get double items in the treasure rooms by lining Jacob and Esau to each take a pedestal. Depending on your experience, you'll know the ways to maximize your runs, which is always helpful. Beyond that, just try to keep the two synced with each other, and learn how to quickly resync them if they become separated, be it via damage or an obstacle.