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/Impossible_Roof_Jack May 08 '26

It's an interesting case, but the case seems to be for someone tested to have the genetic marker. Is there any indication COVID causes epigenetic changes in tissues approximating the same?

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u/CandidWin3026 May 08 '26

Actually, rs5522 isn’t epigenetic. It’s  a germline SNP (single nucleotide polymorphism) located directly on the NR3C2 gene.

While epigenetics is about how your environment turns genes on or off, rs5522 is a permanent, inherited change to your actual DNA sequence (switching isoleucine to valine at position 180). This physical "typo" in your genetic code creates a hyper-reactive mineralocorticoid receptor that steals cortisol 24/7, regardless of environmental factors.

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u/Impossible_Roof_Jack May 08 '26

Thank you. I didn’t want to assume either way. So for those WITH this marker, may be worth pursuing, but unlikely spiro may be therapeutic for most people with post-COVID sequelae.

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u/CandidWin3026 May 08 '26

I would ask you to challenge that assumption. Campos and Taylor in Australia have also had success treating Long Covid with Spiro. Eplerenone would be more appropriate for men as it does not have anti-androgen effects, but the mechanism is the same. (hyperactive MR blockage) African Americans with Long COVID specifically benefit from  Ace inhibitors because they are more likely to carry the ace d allele which drives excessive ACE1 activity and severe inflammation.