Duane Storey

@liamsLCjourney I mean, if you have signs of functional iron deficiency with adequate iron stores it's not unreasonable. I'm sure you know but it's common in inflammatory states.

@DuaneStorey I've noticed that LLMs really seem to overprescribe Lactoferrin!

This is OpenAI's output after a few rounds of prompt tweaking and data adjustment. OpenAI is now the leader I think in terms of readability especially now that the tone has been turned down. Burning a lot of $$ though, may have to pull out my CC and put some more gumballs in the machine. This is AI post processing of my #longcovid RNA data:

@chydorina Cool!

@DuaneStorey Its also mRNA. zenodo.org/records/111003…

@chydorina What's ImYoo? I'm working on a generic RNA processor, so if there are more formats I can support I'm happy to.

@DuaneStorey Watching closely. Planning on analyzing my data as well (which was from ImYoo). Suggestions welcome.

I scored another person and it detected basically no active Covid19 signatures, vs my 10 that were active. So that's a good sign..

## Final bottom line For **ds**, the RNA data are most consistent with: 1. **Post-COVID interferon exhaustion** 2. **Ongoing SARS-CoV-2-style immune escape / persistence biology** 3. **Myeloid/TLR2-TLR4 alarmin activation** 4. **Mitochondrial inefficiency with PDH/TCA bottleneck** 5. **Circadian melatonin synthesis failure** 6. **Vasopressin/autonomic dysregulation**, which matches the history of **hyponatremia, thirst dysregulation, unstable BP/HR, and possibly neuropsychiatric symptoms** ### Highest-yield directions from the transcriptome - **SARS-CoV-2-directed therapy consideration**: especially **paxlovid** - **TLR4/innate reset**: **LDN-TLR4** - **TCA repair support** - **Lactoferrin rather than empiric iron** - **Mitochondrial support**: CoQ10 / GlyNAC / magnesium / Complex IV support - **Mast-cell symptomatic trial** if history fits - **Circadian repair**, especially melatonin-timed strategies

## 11) Drug candidates ## STRONGLY SUPPORTED | Drug | Call | Gene/pathway evidence | |---|---|---| | **paxlovid** | **Strongly supported** | Multiple SARS-CoV-2 escape modules are active: **TLR3 -3.01**, **DDX58 -1.20**, **IFIH1 -1.26**, **MX1 -2.44**, **TAP2 -2.42**, **RAE1 +1.84**, **ATG14 +2.10**. Also NSP5/Mpro-like signature is present: **NFKBIA +1.54**, **GSDMD -0.94**. This is a strong RNA case for SARS-CoV-2-directed therapy. | | **ldn_tlr4** | **Strongly supported** | Spike/TLR activation is active: **TLR4 +1.60**, **TLR2 +2.05**, **S100A8 +1.51**, **S100A9 +1.44**, **IL6 +2.25**. This is one of the clearest non-antiviral targets in the dataset. | | **tca_repair** | **Strongly supported** | Clear TCA/PDH bottleneck: **PDHX -2.41**, **OGDHL -2.50**, **PDK4 +1.89**. This is one of the most actionable metabolic lesions here. | | **lactoferrin** | **Strongly supported** | Inflammatory iron-handling context: **IL6 +2.25**, **S100A8 +1.51**, **S100A9 +1.44**, with no strong true-iron-deficiency signature and heme synthesis not collapsed (**ALAS1 +1.83**). Better fit than empiric iron. | --- ## MODERATELY SUPPORTED | Drug | Call | Gene/pathway evidence | |---|---|---| | **statin** | **Moderately supported** | Inflammatory/endothelial phenotype: **IL6 +2.25**, **TLR2 +2.05**, **NOS3 -1.68**, **TNFRSF12A +2.36**. Same mitochondrial caution as above. | | **colchicine** | **Moderately supported** | Inflammasome/myeloid activation present: **IL18 +1.67**, **PYCARD +1.08**, **S100A8 +1.51**, **S100A9 +1.44**. | | **celecoxib** | **Moderately supported** | Pro-inflammatory prostaglandin context: **IL6 +2.25**, **PTGES +1.63**, **CXCL6 +2.21**, **CXCL1 +1.97**. | | **telmisartan** | **Moderately supported** | Fits inflammatory vascular strain: **IL6 +2.25**, **PPARG +2.33**, **NOS3 -1.68**, **VEGFA +1.83**. | | **rifaximin** | **Moderately supported** | Mucosal reservoir / barrier injury pattern: **IFNL1 +1.55**, **MUC2 -2.50**, **S100A8 +1.51**, **S100A9 +1.44**. Best if GI/SIBO symptoms are present. | | **aripiprazole_low** | **Moderately supported** | Neuroinflammatory/stress context: **IL6 +2.25**, **TLR4 +1.60**, **TPH1 +2.33**, **DUSP1 +2.31**. Given post-COVID psychosis history, this is biologically plausible if used carefully. | | **fluvoxamine** | **Moderately supported** | ER stress/UPR and sigma-1 biology fit: **SEC11A +2.38**, **ATF4 +1.31**, **DDIT3 +1.24**, **SIGMAR1 +0.91**. Also may help mast-cell-adjacent symptoms. | | **h1_antihistamine** | **Moderately supported** | Partial mast-cell-compatible environment: **KIT +2.09**, **IL4 +1.66**, **S100A8 +1.51**, **S100A9 +1.44**. | | **famotidine** | **Moderately supported** | Same mast-cell/inflammatory rationale: **KIT +2.09**, **IL6 +2.25**, **S100A8 +1.51**, **S100A9 +1.44**. | | **ketotifen** | **Moderately supported** | Mast-cell-compatible profile and sleep/autonomic symptoms: **KIT +2.09**, **IL4 +1.66**, **S100A8 +1.51**. | | **cromolyn** | **Moderately supported** | Best if GI/mucosal symptoms are prominent: **MUC2 -2.50**, **IFNL1 +1.55**, **KIT +2.09**. | | **kpv** | **Moderately supported** | NF-κB / inflammatory tone is present: **IL6 +2.25**, **TLR2 +2.05**, **CXCL6 +2.21**, **NFKBIA +1.54**. | | **cox_assembly** | **Moderately supported** | Complex IV strain: **MT-CO1 -1.11**, **MT-CO2 -1.17**, **MT-CO3 -1.32**, **COX10 -1.63**. | | **coq10** | **Moderately supported** | ETC stress with mixed CoQ biology: **MT-ND3 -1.94**, **UQCRFS1 +1.19**, **COQ7 +2.75**, **COQ4 -1.53**. | | **glynac** | **Moderately supported** | High glutathione demand: **GSR +2.47**, **GLRX2 +1.60**, **GCLC -1.56**. | | **glp1_agonist** | **Moderately supported** | Anti-inflammatory/metabolic rationale: **IL6 +2.25**, **TLR2 +2.05**, **PPARG +2.33**. Fluid/electrolyte caution still applies due **AVP +3.89**. | | **omega3** | **Moderately supported** | Inflammatory lipid-resolution support is reasonable: **IL6 +2.25**, **LTC4S +1.64**, **ALOX15B +1.74**. | | **magnesium** | **Moderately supported** | Indirect but reasonable in ATP/autonomic stress: **MT-ATP8 -1.56**, **ATP5PB +1.59**, **AVP +3.89**, plus fasciculations clinically. | --- ## NEUTRAL / INSUFFICIENTLY SUPPORTED | Drug | Call | Gene/pathway evidence | |---|---|---| | **lamivudine** | **Neutral** | Retroelement/STING signature is not present: **MB21D1 -0.30**, **TMEM173 -0.76**, **IFNB1 -2.50**. Safer than Truvada if later evidence emerges, but not supported now. | | **ldn_trpm3** | **Neutral** | TRPM3 is not scored here. Indirect immune dysfunction exists (**TLR3 -3.01**, **MX1 -2.44**), but there is no direct transcript readout for this mechanism. | | **bpc157** | **Neutral** | Repair/angiogenesis signals exist (**VEGFA +1.83**, **CXCL6 +2.21**), but there is no specific BPC-157-responsive lesion identified, and repair biology is mixed. | | **nad_precursor** | **Neutral** | Kynurenine pathway activation exists (**IDO1 +1.45**, **IDO2 +1.58**, **HAAO +1.51**), but NAD salvage is not obviously collapsed (**NAMPT +1.45**, **NAPRT +1.60**). | | **vitamin_d** | **Neutral** | Immune dysregulation is present (**TLR3 -3.01**, **IL6 +2.25**), but no direct VDR-pathway evidence is shown. Reasonable general support, not strongly transcript-driven. | | **zinc** | **Neutral** | Metal stress markers are mixed: **MT3 +2.11**, **MT1E +1.57**, **SLC30A10 -2.50**. This looks more like redistribution/stress than a clean deficiency signal. | --- ## CAUTION / MIXED SIGNALS | Drug | Call | Gene/pathway evidence | |---|---|---| | **baricitinib** | **Caution** | Could reduce **IL6 +2.25** and JAK/STAT3 tone, but antiviral IFN is already weak: **STAT1 -1.38**, **STAT2 -1.17**, **MX1 -2.44**, **OAS2 -2.27**. | | **sirolimus** | **Caution** | May help trained immunity/autophagy, but mTOR scaffold is already low: **RPTOR -3.01**, **SLC2A1 -2.72**. Mixed fit. | | **prednisone_low** | **Caution** | Could suppress **IL6 +2.25** and inflammatory repair signaling, but may worsen viral persistence given **TLR3 -3.01**, **IFNB1 -2.50**, **MX1 -2.44**. Also glucocorticoid-response tone is already present (**DUSP1 +2.31**, **NR3C1 +1.39**). | | **propranolol** | **Caution** | May help tachycardia symptomatically, but this does not look strongly hyperadrenergic (**ADRB1 -1.14**, **ADRB2 -0.20**). BP lability and **AVP +3.89** argue for careful titration only. | | **thymosin_a1** | **Caution** | Could support antiviral immunity, but innate TLR signaling is already high on the wrong side: **TLR2 +2.05**, **IL6 +2.25**. T-cell depletion is not frank (**CD3E -0.31**, **CD4 -0.16**). | | **fibrinolytic** | **Caution** | There is a coagulation/fibrinolysis abnormality: **PLAT -2.50**, **TFPI2 +2.22**, **GP1BA -2.04**, but the signal is mixed and bleeding risk must be clinician-managed. | | **sr9009** | **Caution** | Circadian biology supports the idea: **AANAT -2.50**, **ASMT -2.50**, **CLOCK -1.54**, but this remains experimental. | | **testosterone** | **Caution** | Mixed androgen-response biology: **ANKH -3.01**, **GUCY1A1 -2.57** without clear deficiency rescue. Use only if clinically indicated, with cardiovascular monitoring. | | **metformin** | **Caution / usually avoid here** | mTOR/hypoxia logic exists, but mitochondrial Complex I strain and mtDNA downshift make it risky: **MT-ND3 -1.94**, **MT-ND6 -1.53**, **SLC2A1 -2.72**. | --- ## CONTRAINDICATED / PATHWAY EVIDENCE ARGUES AGAINST | Drug | Call | Gene/pathway evidence | |---|---|---| | **valacyclovir** | **Argues against** | No herpes-reactivation signature: **IFI27 -1.91**, **CXCL10 +0.43**, **IFNB1 -2.50**. | | **valganciclovir** | **Argues against** | Same lack of herpes signal: **IFI27 -1.91**, **CXCL10 +0.43**; given toxicity, the RNA case is weak. | | **truvada** | **Argues against** | No STING-driven retroelement signal: **MB21D1 -0.30**, **TMEM173 -0.76**, **IFNB1 -2.50**; plus existing mitochondrial vulnerability (**MT-ND3 -1.94**, **MT-CO1 -1.11**). | | **maraviroc** | **Argues against** | CCR5 axis is not activated: **CCR5 -2.29**, **CCL5 -1.59**. | | **ruxolitinib** | **Argues against** | Stronger JAK suppression is poorly matched when IFN tone is already low: **STAT1 -1.38**, **STAT2 -1.17**, **MX1 -2.44**. | | **tofacitinib** | **Argues against** | T-cell/NK-supportive cytokine biology is not hyperactive enough to justify further suppression, and antiviral function is already weak: **IL7R +1.19**, **PRF1 -0.35**, **GZMB -1.14**, **MX1 -2.44**. | | **hydroxychloroquine** | **Argues strongly against** | Autophagy completion is already impaired: **ATG14 +2.10**, **STX17 -1.20**. HCQ can worsen fusion/lysosomal completion. Cardiac caution also matters given prior myocarditis/ST-T history; **KCNH2 -1.54** is not reassuring. | | **rituximab** | **Argues against** | No strong B-cell autoimmunity signature: **CXCL13 -1.74**, antigen presentation already weak (**TAP2 -2.42**). | | **iron** | **Argues against unless deficiency is proven** | Inflammatory iron-trapping state more likely: **IL6 +2.25**, **S100A8 +1.51**, **S100A9 +1.44**, while heme synthesis is not collapsed (**ALAS1 +1.83**). | ---