Post-exertional malaise is a delayed or prolonged worsening of symptoms after physical, cognitive or emotional exertion. Understanding its biology is critical to understanding ME/CFS.

What changes when blood is tested before and during PEM? 🧵 A resting blood sample gives one snapshot. Testing the same person before and after exertion lets researchers see which signals move as symptoms are triggered, rather than only comparing average patient and control groups.

In fibromyalgia, severe irritable bowel symptoms were linked with fewer tiny nerve fibers in skin biopsies. The study connects gut symptoms with a measured change in nerves that also help control pain and automatic body functions. The study included 89 people with fibromyalgia. Fifty-seven also had a skin biopsy, where a very small piece of skin is removed and examined under a microscope.

Viral persistence and viral reactivation are often discussed together in Long COVID and ME/CFS, but they are not the same process. One concerns the original virus. The other concerns older latent viruses becoming active again.

Let's break it down 🧵 Persistence means material from SARS-CoV-2 remains after acute infection. This could be whole virus, low-level replication, viral proteins or leftover RNA fragments. These are not the same thing and may have very different effects.

I spent about a month in bed, blindfolded, wearing ear defenders, barely speaking, and unable to tolerate normal light or sound.

What happened to my brain during that time was unexpected and extreme.

This is what it was actually like. The illness was ME/CFS after developed after a COVID infection in 2021. I was originally completely healthy, 21 years olds and athletic, but after the infection, continuous progressive neurological symptoms began.

Low blood volume has been reported in a subset of people with ME/CFS, especially those who feel worse when standing. With less blood circulating, it may be harder to keep enough returning to the heart and reaching the
brain.

Let's break it down 🧵 Blood volume includes plasma, the liquid part, and red blood cells. A routine blood count can still look normal because it measures concentration, not the total amount of blood moving around the body.

Red blood cells may be disrupted during acute COVID, with further abnormalities reported in Long COVID and ME/CFS. They carry oxygen and must squeeze through tiny vessels. If they change shape, stiffen or break apart, blood flow may be affected. 🧵 A healthy red blood cell is soft and flexible. It folds to pass through capillaries, some narrower than the cell itself,then springs back into shape. This helps oxygen reach tissues throughout the body.

People have asked where my optimism comes from for improving my Long COVID in the next 2-3 years.

First, what it isn’t: I don’t think a blanket cure for ME/CFS or long COVID is coming in the near term, & I don’t expect a clinical trial to necessarily pass phase 3.

What it is🧵 A JAK-STAT inhibitor like baricitinib might, if the effect is wide enough.

We’ll see.

But that’s not where my optimism lives. It’s more nuanced than “one drug fixes everyone.”

Two of the main biological theories being studied in Long COVID are autoimmunity and viral persistence. Both can produce ongoing inflammation and immune activation, so separating them may be difficult.

Let's break it down🧵 Autoimmunity means part of the immune response reacts against the body's own molecules, cells or receptors. Viral persistence means SARS-CoV-2 material or activity remains after the acute infection.

Children with post-COVID illness had wider tiny arteries and veins at the back of the eye. After adjustment, the arteries were about 28 micrometers wider and the veins about 22 micrometers wider than in matched healthy children. The study recruited 74 children with post-COVID illness. The main vessel-width comparison used 58 of them and 58 healthy controls matched for age, sex and body mass index.

Antibodies from people with neurological Long COVID produced fatigue-like behavior, balance problems, pain sensitivity and small-nerve damage when transferred into mice. This provides direct evidence that harmful
antibodies may contribute in a subgroup. Antibodies are immune proteins that recognize targets. Autoantibodies are antibodies that react with the body's own cells or proteins.

Blood vessel inflammation linked to brain fog. A new study found signs of blood vessel inflammation in people with neuropsychiatric Long COVID, linked with worse memory, word finding, anxiety, and depression.

Let's break it down in simple language 🧵 Researchers compared 28 people with acute COVID, 50 people with neuropsychiatric Long COVID, and 29 people who recovered after COVID. They also checked a separate Johns Hopkins group with later Long COVID, around 3 years after infection.

New long COVID research in children and young adults found signs of blood vessel injury, tiny abnormal blood clots, and overactive neutrophils, a type of white blood cell that can damage vessel lining when activated. The study included 84 people aged 25 or younger: 61 with long COVID and 23 healthy controls. The long COVID group had common circulation-type symptoms, including dizziness when standing, shortness of breath on stairs, and palpitations.

🔬Study shows SARS-CoV-2 causes direct damage to heart cell mitochondria - even months after recovery - helping potentially explain Long COVID heart symptoms like chest pain, palpitations & fatigue.

Let’s break it down 🧵 Researchers studied 5 people who had COVID-19 weeks or months earlier. They all had new or unusual heart problems, like chest pain, irregular heartbeat, or even cardiac arrest.

Each patient had a heart biopsy (a sample of heart tissue examined under a microscope).

New long COVID study suggests tiny packets released by gut bacteria may help drive gut problems, immune activation, and brain-related symptoms in some people with long COVID. This study focused on extracellular vesicles. In simple terms, these are tiny packages released by bacteria and other cells. They can carry different materials and may send signals from the gut to other parts of the body.

A new ME/CFS study found signs that people with more severe illness may show different spinal fluid protein patterns linked to immune activity, blood clotting, cell stress, and brain-related signaling. People with POTS also showed a different pattern. Simple breakdown 🧵 The study looked at cerebrospinal fluid, or CSF. That is the fluid around the brain and spinal cord. The researchers wanted to see whether CSF proteins differed by ME/CFS severity and by whether someone also had POTS.

The strongest new mast cell-targeting drugs are in CSU, and the best of them may represent potential remission-level treatments for central mast cell diseases by directly reducing the pathological cell rather than just blocking one pathway. CSU is chronic spontaneous urticaria.

In simple terms, it is long-lasting hives and sometimes swelling without a clear trigger. It is one of the clearest human diseases where mast cells are known to play a central role.

Two recent stories suggested AI may help find highly personal treatment routes in cancer, one in Sid Sijbrandij and one in Rosie the dog. There is some nuance here, so I’ll break down what happened in simple language, including cost, and how similar logic could apply to chronic disease. The key point is not that AI acted like a robot in a lab. It is that AI helped do discovery work. It processed large amounts of biological data, linked them to past research, and helped narrow down specific treatment routes that were then tested in real life.

A new brain scan study found widespread inflammation-related changes across the brain’s wiring in ME/CFS, and some matched worse mental health, more disability, and greater illness severity. Older ME/CFS brain scans often disagreed. The usual method can show change, but not clearly whether it means extra fluid, extra cells, damaged fibres, or something else. This also builds on earlier blood and brain-scan work that hinted at inflammation.

A study of 40,537 people found key immune cells that fight infections were still below earlier levels up to 20 months after the major COVID wave. In people with heart and blood vessel disease, some of these cells were about 70% lower than earlier levels. The paper looked at lymphocytes, which are white blood cells that help fight infection.

T cells help organize the response and can kill infected cells.
B cells make antibodies.
NK cells are fast-acting white blood cells.
CD4 and CD8 are two main T-cell groups.

Pieces of SARS-CoV-2 proteins were found in tiny blood particles in many people with long COVID, even about 17 months after infection. This may point to a measurable biological signal, not just symptoms. Breakdown in simple language 🧵 Those tiny particles are extracellular vesicles (EVs). EVs are small packages released by cells into the blood that can carry proteins and other material.

A study found a small set of molecules in blood that can separate people with Long COVID from recovered patients 1 year after severe infection.

Using machine learning on metabolomics data, researchers identified 9 molecules linked to energy problems in the body. The study looked at people who were very sick with COVID and needed ICU care.

About 1 year after leaving hospital, researchers compared two groups:

21 people with ongoing Long COVID symptoms
21 people who had recovered.