New research has identified a potential biological cause for post-COVID fatigue/muscle fatigue.

Scientists found that a molecule called soluble IL-2 receptor (sIL-2R), linked to immune activation, may directly harm mitochondria in muscle cells. Two studies led by Brown et al. (a 2024 preprint and a 2025 peer-reviewed paper) examined blood and muscle samples from people with long-COVID fatigue compared to healthy controls.

Elevated Angiotensin II (AngII) in ME/CFS & Long COVID patients:

Ang II controls blood pressure and circulation. It can also affect insulin use in muscle, activate brain immune cells, and more.

Let’s breakdown the findings in simple terms 🧵 Ang II helps control blood pressure, circulation, and inflammation.

Too much Ang II can narrow blood vessels and increase stress inside the vascular system.

ROCK2 protein levels reduced in post-exertional malaise (PEM) ME/CFS and Long COVID cohort:

Patients who had blood drawn during PEM had significantly reduced ROCK2 than those who had blood drawn at baseline.

Preliminary finding. ROCK2 is an enzyme that helps control blood vessel tone, platelet function, and immune cell signaling.

It’s mainly inside cells, so changes in serum may be more complicated than simply just reduced protein levels.

🧵A new study analyzed blood from people with hypermobile Ehlers-Danlos syndrome (hEDS) and found strong evidence of immune dysfunction.

Complement proteins were consistently lower, cytokine signaling was altered, and structural collagen markers were normal. Researchers used mass-spectrometry and ELISA to compare 29 hEDS patients with 29 matched controls.

The results showed widespread immune and inflammatory changes, suggesting hEDS involves more than connective-tissue abnormalities.

🧵Super interesting new paper by @Jgburgess2 & Co: How IgG autoantibodies may cause fibromyalgia via mast cells.

Summary: IgG from fibromyalgia patients activates mast cells via the MRGPRX2 receptor, triggering inflammation & pain. Blocking this pathway could offer treatment. The researchers took IgG (an antibody type) from fibromyalgia (FMS) patients and injected it into mice.

The mice developed symptoms seen in human fibromyalgia: heightened pain from touch and cold, lower movement, and gut issues.

IgG from healthy people had no effect.

New interesting research POTS paper:

A large proportion of people with POTS - including those who developed it after COVID - have a measurable blood abnormality: a platelet storage pool deficiency.

Let’s breakdown what that means in simple terms.🧵 POTS (Postural Orthostatic Tachycardia Syndrome) is a condition where standing up leads to a large increase in heart rate, dizziness, fatigue, and other symptoms.

It’s now common in long COVID.

Up to 80% of long COVID patients may meet POTS criteria.

🧬 New finding from our @amaticahealth Long COVID & ME/CFS cohort:

We found elevated levels (P = 0.0351) of free TGF-β1 in Long COVID & ME/CFS serum samples.

This protein has been found elevated in multiple Long COVID & ME/CFS studies & may correlate with a subgroup. 🧵 TGF-β1 is a protein that regulates the immune system, tissue repair, and inflammation.

When free (active) TGF-β1 is elevated, it may affect how the immune system responds to infection, tissue injury, or chronic inflammation.

🧬 New finding:

Low serum ROCK1 levels have been identified in our Long COVID and ME/CFS @amaticahealth cohort.

ROCK1 is a regulatory protein involved in stress response, immune activity, and autophagy (cell recycling). Possibly having relevance in disease mechanisms. ROCK1 is a protein found inside cells. It helps regulate how cells move, contract, and respond to signals - including stress, inflammation, and damage.

It’s involved in multiple systems: immune, cardiovascular, neurological, and metabolic.

🔬❕We found reduced ACE protein levels in the blood of people with Long COVID & ME/CFS.

This could affect blood flow, fluid balance, inflammation, & brain function - potentially relevant to symptoms like orthostatic intolerance, brain fog, & chronic pain.

Let’s break it down. ACE (angiotensin-converting enzyme) plays a key role in blood pressure, fluid balance, and inflammation.

It converts angiotensin I to angiotensin II, and also breaks down bradykinin and substance P - both of which affect pain, blood vessels, and immune signaling.

🔬Most people think mast cells are only involved in allergies or rare conditions like MCAS or mastocytosis. That’s incorrect.

Research shows mast cells are active in many diseases, including neurodegenerative, autoimmune, infectious, heart, gut, and mental health conditions🧵 Mast cells sit in tissues like the skin, gut, and around blood vessels and nerves. When triggered, they release a large mix of chemicals: histamine, tryptase, chymase, cytokines (like TNF and IL-6), prostaglandins, and more.

These chemicals affect nearby cells and tissues.

🧵 T cell exhaustion - possibly one of the drivers of chronic infections in Long COVID & ME/CFS.

What is it, what genes are involved, and how we can gain insights with available testing.

Let’s break it down. 🧵 T cells are immune cells that normally help fight infections and cancer.

But when T cells are exposed to a threat for too long - like a virus or tumor that doesn’t go away - they can enter a state called “exhaustion.”

Started exploring EBV RNA markers in our @amaticahealth ME/CFS & Long COVID RNA-seq cohort.

Focused on EBNA1, which is typically expressed during EBV latency.

Will explain in simple terms below, but really cool possible finding and shows the utility of having all mRNA 🧵 EBNA1 was unexpectedly low in many ME/CFS samples. Our 3 controls showed higher levels, which is more in line with what you’d expect if EBV is active (without context).

Important caveat: we only have 3 controls right now, so this difference could shift with more data.

🔬 A new study sheds light on why people with Myalgic Encephalomyelitis (ME) experience post-exertional crashes and brain fog.

It focuses on a blood protein called haptoglobin (Hp) and how its different genetic forms affect symptoms. 🧵 ME is a chronic illness where even minor physical or mental effort can cause days of worsened symptoms - called post-exertional malaise (PEM).

This study explored how the body’s response to stress might be linked to the haptoglobin protein.

🔬 A new study looked at RNA inside the spinal fluid of women with neuropsychiatric Long COVID (brain fog, etc) to understand what’s going wrong in the brain.

Let’s break it down 🧵

You can also test your RNA in blood here:

amaticahealth.com/me-cfs-long-co… Researchers compared immune gene activity (RNA) in spinal fluid (CSF) and blood from women with Long COVID vs. women who had COVID but recovered fully.

They wanted to see if immune changes in the brain were different from those in the rest of the body.

🔬 A large genetic study just found links between specific immune receptor variants (called KIR alleles) and ME/CFS.

And into DecodeME findings.

Simplified breakdown 🧵 ME/CFS is a disabling disease that affects energy, memory, sleep, and physical function.

Many cases begin after an infection.

Its biological causes are not completely known, but immune system problems - especially involving NK cells - are a main theory.

🔬Can we understand the health of the blood-brain barrier (BBB) from a simple blood draw?

According to research, yes - by sequencing RNA in whole blood, we can detect changes in genes that affect or reflect BBB function

Here’s how it works and how it’s been done in research 🧵 The BBB is a protective layer of cells around the brain’s blood vessels. It blocks harmful substances from entering the brain while letting nutrients through.

When the BBB is damaged or leaky, it’s linked to many brain conditions - from Long COVID to Alzheimer’s.

Leaky gut is when the barrier in your intestines becomes too porous, letting bacteria, toxins, or food particles slip into your bloodstream.

This thread breaks down what mRNAs are involved in that process - in plain language and how you can test yourself:

amaticahealth.com/me-cfs-long-co… Your gut lining is made up of cells tightly joined together. These junctions act like seals.

Certain genes produce proteins that hold those seals in place.

In leaky gut, those genes often turn down or off, weakening the barrier.

A new study just showed that gut bacteria from people with fibromyalgia can cause pain when transplanted into mice.

This is the strongest evidence yet that the gut microbiome plays a direct role in fibromyalgia.

Here's a full breakdown of what they found Fibromyalgia (FM) is a chronic pain condition.

It causes widespread pain, fatigue, sleep problems, and often depression.

But unlike arthritis or nerve injuries, FM has no clear physical cause. That's why it's called “nociplastic” pain - pain without damage.

New @amaticahealth preliminary findings: elevated NKG2A in Long COVID & ME/CFS

NKG2A is a receptor found on NK cells & some T cells. It acts as an "immune system brake" when on

This is useful for preventing damage to healthy tissue - but can prevent proper clearance of viruses @amaticahealth NKG2A works by detecting a protein on cell surfaces called HLA-E.

When HLA-E is present, NKG2A sends a signal that tells the immune cell to stop. This helps prevent the immune system from attacking the body’s own cells.

New research shows Long COVID and chronic fatigue syndrome (ME/CFS) share the same biological problem: their bodies struggle to use oxygen properly during exercise.

Here's a full breakdown - and what it means. Researchers studied 3 groups:

- 15 people with Long COVID

- 11 with ME/CFS

- 11 healthy people

They all did intense exercise tests while hooked up to tubes and catheters that measured heart and lung function in real time.

Reposting as important:

🔬 Mitochondria help power cells, and they constantly split (fission) and join (fusion) to stay healthy.

Surprisingly, we can track how this is going using blood RNA.

Here’s what recent research has found in humans 🧵 First, the main genes to know:

- MFN1, MFN2, OPA1 -> control fusion (joining)

- DRP1, FIS1 -> control fission (splitting)

Their RNA levels in blood tell us whether cells are leaning more toward breaking apart mitochondria or keeping them intact.