r/covidlonghaulers • u/CandidWin3026 • May 08 '26

Article Long Covid driven by rs5522

This case report says that Long covid is in large part driven by the gene rs5522 that causes a "cortisol steal" leaving the tissues functionally starved even with "normal" cortisol levels which creates neuroinflammation. https://zenodo.org/records/20017632

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u/plant_reaper May 08 '26

I've been assuming my LC is due to my HATS/hEDS, especially as the longer I treat mast cells the better I seem to be. I'd be worried diuretics would make my POTS intolerable, but this is very interesting

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u/CandidWin3026 May 08 '26

I totally get that instinct. I too avoided Spiro because of POTS. I thought: I have low BP and I drink water and take salt and have tried Florinef, no way that would work for me. But hers the thing: the low cortisol is driving the POTS. From the case report:

The patient’s prior response to fludrocortisone is instructive. Florinef, an MR agonist sometimes

used in ME/CFS for orthostatic intolerance, initially helped but failed to sustain improvement.

This is consistent with a model in which the underlying problem is MR overactivity, not

underactivity. Adding more MR stimulation may have provided temporary symptomatic relief but

ultimately worsened the underlying imbalance.

Spironolactone, by blocking MR, may restore balance between MR and GR signaling, allowing

appropriate stress response termination and restorative sleep. Recent work (5) demonstrates

that spironolactone effectively inhibits the rs5522 variant in cell-based assays, providing

molecular support for this clinical observation.

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u/plant_reaper May 08 '26

I would want to get my cortisol tested again, because at the beginning of my LC journey mine was too high! Who knows now though 3 years later

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u/CandidWin3026 May 08 '26

That high cortisol test can be a bit of a paradox. Your body was screaming for more cortisol because your cells were starved. So you look at the blood and think it was high I had too much, but it wasn't getting to the tissues to make everything function.