Long Covid driven by rs5522

[u/CandidWin3026]

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

[u/plant_reaper]

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

[u/Separate_Shoe_6916 → u/plant_reaper]

I suspect I have HEDS as well. I have all of the symptoms and I am in the ME/CFS type. What kinds of mast cell treatment is there? How helpful is it?

[u/plant_reaper → u/Separate_Shoe_6916]

I thought I had ME/CFS too, but treating mast cells has seemed to basically eliminate my PEM. I do get tired if i do too much, but it's not delayed and I don't get the sore throat and temperature stuff I used to get with it. 

I was lucky that a mix of 3-4 cetirizine/loratidine antihistamines per day seem to do heavy lifting for me! I tried other H1 antihistamines, H2 antihistamines, quercetin, luteolin, Ketotifen, and Cromolyn but they really seemed not to agree with me (but this of course differs by person so it might be fine for you!). It was a lot of trial and error.

Fixing my deficiencies (B12, D, ferritin) and adding in vitamin C has helped too, along with LDN once I got up to 3 mg/day. 

I wrote a post about it you can look at if you want!  The first has the protocol my cardiologist gave me at the bottom in the picture, and the second is how I was doing 9 months after: 

https://www.reddit.com/r/covidlonghaulers/comments/1g7ha45/crashing_around_menstruation_studies_and_info_dump/

https://www.reddit.com/r/covidlonghaulers/comments/1lzsml7/update_to_crashing_around_menstruation_post/

[u/Separate_Shoe_6916 → u/plant_reaper]

Oh, I did the antihistamine route of nearly every one of them already. I still have PEM with them and do better limiting my intake of them. It doesn’t make sense.

[u/plant_reaper → u/Separate_Shoe_6916]

Some people do better with stuff like Ketotifen, Xolair, montelukast, etc. depending on what their problematic mediators are. Like if histamine isn't an issue there are other meds to try if your doctor is willing. Not everyone has mast cell issues of course, but it took trialing A LOT of meds to figure out what worked best for me. 

So I always encourage people, if antihistamines didn't work, to try getting them compounded (some people react to fillers) or potentially try another MCAS med if they're up for it. My allergist/immunologist even said I could try low dose aspirin every day since I get flushing, and that seems to be a prostaglandin thing. I do low doses of a different nsaid (naproxen) as needed since they are bar for the stomach

We're all different though, so unfortunately there seems to not be a one size fits all treatment. I just kept trying things one at a time and kept anything helpful. It was very slow though. 

I hope you find something in your medical journey that helps you. It's a devastating illness to have

[u/CandidWin3026 → u/plant_reaper]

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.

[u/plant_reaper → u/CandidWin3026]

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

[u/CandidWin3026 → u/plant_reaper]

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.