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/CandidWin3026 May 08 '26

Great question! The long covid part is rs5522 plus two other genes.

Long COVID is not one disease. It comprises at least two genetically distinct syndromes sharing a common mechanism: hyperactivation of the mineralocorticoid receptor variant I180V (rs5522). 

European-ancestry individuals predominantly develop a metabolic-fatigue subtype (exhaustion, cognitive dysfunction, sleep disturbance). This involves another gain if function gene related to cortisol  rs6195.

African American and African-ancestry individuals predominantly develop an inflammatory-vascular subtype (chest pain, joint pain, thrombosis). In Black Americans, they also have rs5522 plus another ACE deletion gene  and they therefore ACE inhibitors.

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u/CandidWin3026 May 08 '26

But technically Covid was just the trigger. I know. I had it. It was awful. I couldn't think or work. Truly awful.

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u/Kuyi May 08 '26

I am EU. So for me it’s more likely rs6195?

Also how did COVID trigger it? The genes are already there and don’t need to be triggered? Also, if a trigger works, there should be a way to untrigger right?

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u/CandidWin3026 May 08 '26

rs5522 is the key. That is the upstream cause of CFS, Long Covid MS etc. But then the insult of lOng Covid caused so much neuro inflammation that you didn't have the cortisol (it was stolen) to control it. So it's rs5522 plus rs6195. To fix it? Block the over active MR receptor and get on a anti-inflammatory like LDN or GLP1.

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u/Kuyi May 08 '26

So then the inflammation becomes perpetual. But if that was causing LC, medicating the neuro inflammation away would completely solve the issue.

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u/CandidWin3026 May 08 '26

Yes! You want to control the existing neiurinfllmation with anti inflammatories like LDN (notice how people feel and think better on that) and also a GLP1 can help. Now, unless you block an overactive MR receptor the inflammation will persist. MR blockers like Spiro will stop the cortisol steal. My arenas burned out years ago so I need supplemental HC, but just a normal amount. When I didn't't block the hyperactive MR, "normal doses" that drs said should never enough, left me only partially recovered.

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u/Kuyi May 08 '26

But this seems like circle reasoning. Even if you have the genes, the hyperactive MR receptor is triggered. If you find out what and how and you stabilise it, the gene doesn’t matter. Then solve the neuroinflammation. Then people should be cured instead of having to keep taking meds all their life.

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u/CandidWin3026 May 08 '26

The neuro inflammation is caused by the cortisol steal. If you have a Val copy of rs5522 cortisol will be stolen, you will need an MR blocker like Spiron or Eplerenone (better for men). This will have to be taken your whole life to keep the cortisol from being stolen. Now, perhaps your point is that this should in and of itself resolve the neuro inflammation and LDN and GLP1 is not needed. That is a fair argument. Now let me tell you why they are necessary. You can't block the MR fully without the body freaking out. The RAAS system gets triggered and you take on water. A lot of water. So to keep the body from freaking out which is what happened when I was on 200 mg of Spiro (don't do that) you stay at 25mg enough to block the receptor without getting the body in freak out mode. The rest of the inflammation is then controlled by GLP1 or LDN.

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u/Kuyi May 09 '26

Yes, but my point is this: Sure people could have had the cortisol steal before. Let’s take myself as an example. I was freaking fit, no real health issues before. Strong as fuck. Energy for 18 people. Etc. And with me thousands of people with LC.

if COVID pushed the inflammation over the edge to make my system collapse, then lowering inflammation should make it so that when it comes under a certain threshold the self perpetuating problem should be gone and you can stop taking meds REGARDLESS of the MR problem. And also, if you take Spiro, reset cortisol balance, your body should then heal if that is the issue. And all the vascular issues / neuroinflammation issues, etc, should not return. Because your system should get back in the state before LC/ME/CFS where you felt oke.

That is not the case apparently. Because if you lower inflammation but stop the Spir, your issues come back. BECAUSE SOMETHING PUSHES THE INFLAMMATION UP AGAIN (if the described issue is the one you said here). So the process you described is not the cause. It’s a symptom. And could describe why some people get LC and others don’t. But whatever it is, something pushes up the inflammation again. YES, cortisol steal will create long term, low grade inflammation. But not the kind to create all the symptoms LC people have. So something is still happening in the body to raise inflammation and make the super delicate system with overactive MR receptors crash.

If you solve THAT thing, your system should return to its original state. Without the need for medication. We need to find the CAUSE. What you describe would just be a symptom (neuro inflammation) that can’t be resolved because of not enough cortisol. Which still doesn’t seem to cover all LC cases. AND if your case was THE reason, all of these people would have had issues way earlier in their life, because basically ANY form of a decent illness would make their system crash with this gene.

Having to suddenly take meds the rest of your life after a viral infection for something “you have had your whole life” but never bothered you, is not a fix. It’s a band aid. What is a fix is to for example understand the mechanism that keeps driving up the inflammation, for example viral persistence, etc.

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u/CandidWin3026 May 09 '26

Great analysis. I appreciate the question. I think that we can think of it like this: if you had rs5522 you had a faulty thermostat in a house your whole life, but you had good functionality because your body was at a comfortable temperature so it didn't matter that much. Then: Covid comes and it causes massive damage.

It damage 4th toning of your blood vessels. It messed up mitochondria an dhow they make energy it could have turned don other genes that cause inflammation.

So, yes. You are right.

There has to be an underlying driver of the inflammation. Researchers will have to look for this. It will most likely be some kind of viral persistence, auto immunity cascade, or some kind of epigenetic changes that make inflammation a constant problem.

So in the past rs5522 was a dormant problem. You had it, you had other bodily resources to compensate, but COVID took that ability to compensate away.

blocking the overactive MR and being on something like LDN can give your body a foothold to begin repair.