3 Biological Neuroimmune Subtypes in Post-COVID & ME/CFS 🔬❕

We mapped our @amaticahealth post-COVID + ME patients into three distinct biological clusters using Neuroimmune markers

Cluster 1; mitochondrial stress
Cluster 2; Non inflammatory
Cluster 3; Neuro inflammatory

🧵 👇🏻 How we did it:

• Serum & Plasma biomarker panel → neuro, immune, RAS & neuro mito markers

• Unsupervised Euclidean clustering → C1, C2, C3

Markers used for clustering:

- NEFL
- S100b
- PINK1
- DRP1
- BH4
- Serotonin
- Rock1
- Rock2

So there was a lot of talk recently about a paper discussing COVID-19 micro-clotting.

I thought I’d break it down in simple language.

The paper looked at why tiny blood vessels get blocked in severe COVID-19. They discovered, it is not the usual clots we hear about. 🧵👇🏻 Inside capillaries, the “wall” is a layer of endothelial cells. When these cells die suddenly, they leave rough patches that blood cells can stick to.

🔬Low serotonin in ME/CFS & Long COVID - what could explain it?

Within our community 1 energy metabolism group, a trend to low serotonin was seen, what could explain this?

🧵👇🏻 Brief reminder:

We split our ME/CFS and Long COVID cohort into communities based on how closely related their metabolism markers were.

We ended up with 2 main groups.

Community 1 having mitochondrial stress markers high - the others, not as much.

🧵 COVID Isn’t Over - Even If You Feel Fine Post Infection

Even mild cases with no immediate long lasting symptoms can cause lasting immune changes.

After the 1918 flu, Parkinsonian illness spiked. Decades later, H1N1 was linked to dementia and Parkinson’s. COVID-19 likely will have similar outcomes.

Studies show even mild infections can leave the immune system inflamed and fatigued months later.

The damage is often silent - but significant and ongoing.

🧵In our metabolic subgrouping, two distinct clusters appeared showing the variability of ME/CFS and Long COVID.

Two different biomarker profiles, each able to lead to similar pathological issues.

These differences can be what drives drug response differences in patients.

1/ In our data, two clear groups show up

• Group 1: high markers of hypoxia and mitochondrial stress

• Group 2: normal mitochondria, but high vascular stress and low nitric oxide production hints

🧵We clustered our patients based on metabolic / O₂-sensing / mitochondrial markers.

Two distinct subgroups appeared, showing potential differences in underlying metabolic function.

We also looked at which other markers separated them.

Here’s what we found 👇

@amaticahealth


The metabolic/mito markers we used:

• HIF1a (hypoxia)
• PINK1 (mito recycling)
• DRP1 (mito fusion)
• SIRT1 (mito stress adaptation)
• GDF15 (mito health)
• TWEAK (exercise intolerance)
• BH4/BH2 ratio (NO signalling)
• Serotonin (neuronal mito health)

So how do my recent @amaticahealth markers potentially fit me into the Itaconate Shunt theory?

The potential driver IFNa (roughly 10x control)

HIF1a, PINK1, Arg1, PGE2 all signs of potential downstream pathology

Let’s break it down 🧵👇🏻

https://twitter.com/jackhadfield14/status/1922239616695882140

Quick recap:

Your mitochondria normally run the TCA/Krebs cycle.

Under threat, immune cells take a detour: IRG1 converts cis-aconitate → itaconate.

That detour = the itaconate shunt.

With my recent results from the @amaticahealth panel, I’ve had a lot of people mention specific theories I may fit into, so I thought I’d break them down!

• Itaconate Shunt Theory (Davis & Phair Theory)

What is it and what does it mean?

🧵👇🏻 Infections make you feel exhausted.

This occurs because your immune cells may be diverting energy through a “detour” known as the itaconate shunt, aiming to starve pathogens but temporarily reducing your energy supply.

New Research Post 🔬❕

47.1% of ME/CFS & Long COVID patients had elevated ANG II compared to all controls.

Correlation between ANG II and NEFL (P<0.0001), potentially linking ANGII levels with neuroinflammation

🧵👇🏻
Ang II is part of the renin–angiotensin–aldosterone system (RAAS). It raises blood pressure, tells your body to retain salt & water, and boosts thirst.

It’s essential for survival — but too much of it can be detrimental

The most common question I get as a researcher:

“Do you think ME/CFS and Long Covid are treatable?”

My short answer: Yes.
My long answer: Read on. We constantly see anecdotes of recovery.
And interestingly, many of them involve the same categories of drugs:

— Antivirals
— Immunosuppressives
— Benzos
— Anticoagulants
— Metabolic drugs (like Metformin)
— ARBs

Etc.

New Results Article - Elevated PINK1 in ME/CFS & Long COVID 🔬❕

Finally finished the article breaking down our PINK1 findings in patients:



PINK1 is a protein key to mitochondrial quality control and mitophagy (recycling of the mitochondria)

🧵 ⬇️ amaticahealth.com/blog/pink1-ele…
What does PINK1 do?

PINK1 normally tags damaged mitochondria for recycling by recruiting PARKIN. When mitochondria malfunction, PINK1 accumulates, signaling the cell to clear out the damage and restore energy balance.

A Unifying Theory to Resolve the Renin-Aldosterone Paradox, Low Cortisol, and Low Blood Volume in POTS, ME/CFS, and Long COVID🔬

TGF-β1–Mediated Adrenal Suppression

My theory on what is going on 🧵👇🏻 Normally, if blood volume is low, the body should ramp up renin & aldosterone to retain salt & water.

But in POTS, ME/CFS & Long COVID, these hormones stay low or normal, despite clear signs of low blood volume.

This is known as the “renin-aldosterone paradox”

Just a reminder. We are accepting patients worldwide for batch 2 of our 31 marker ME/CFS and Long COVID patient funded blood panel



Cost is £1125 per patient & you get your results & research surrounding them alongside

The panel covers major systems 👇🏻 amaticahealth.com/me-cfs-long-co… The markers cover different systems implicated in ME & LC

- mitochondria
- vascular
- neuro inflammation
- immune system
- virus related
- neurochemical
- exercise intolerance
- mast cells

And more

Hypothesis breakdown - Pseudo Hypoxia 1️⃣

Pseudo-hypoxia is where cells behave as if they’re oxygen-starved even when O₂ is normal

In ME/CFS & Long COVID, cells can’t meet energy demands through regular aerobic respiration

🧵 👇🏻

{text} = simplified

https://twitter.com/jackhadfield14/status/1894800283621834922

In ME/CFS, mitochondria—especially Complex V—struggle to synthesize ATP efficiently, meaning normal oxygen levels don’t yield enough energy.

{cell’s energy factories aren’t working well, so they don’t produce enough power}

ChatGPT Deep Research response analysis🔬

 “Hypoxia & Mitochondrial Dysfunction in Post‑Viral fatigue Syndromes.” 

I fed deep research 10 key papers, plus prompted to find additional sources and look into why HIF‑1α and PINK1 are so closely linked in ME/CFS and Long COVID 🧵 Both ME/CFS and Long COVID patients show problems with energy production and inflammation. 

Research finds that HIF‑1α (which signals low-oxygen stress) is raised in a subset of patients, but not as a disease significantly and PINK1 (which marks damaged mitochondria) is significantly elevated as a disease population (p <  0.0171 ), but with an evident sub population showing a notable increase compared to the control and other patients 

Hif1a and PINK1 strongly correlated (p < 0.0001)

Research from @amaticahealth

New results post 🔬❕

Our latest findings on Neurofilament Light Chain (NEFL) levels in ME/CFS and Long COVID patients are now released! 🧠



@amaticahealth

🧵 amaticahealth.com/blog/nefl/

🔬 Key Highlights:

• No overall difference in NEFL levels between patients and controls (P=0.7171)

Potential subgroups identified:

• 20% of patients elevated NEFL vs control

• 30% of patients low NEFL vs control