Subject: POTS, ME/CFS, and Long COVID Are Being Reclassified — Here's What That Means
From: Derek from Research Radar <[email-masked]>
To: [email-masked]
Date: Mon, 13 Apr 2026 15:17:06 +0000
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View this post on the web at https://derekpruski.substack.com/p/pots-mecfs-and-long-covid-are-being

Before diving in: all content shared here is for educational and research purposes only. This is not medical advice. Always do your own research and consult a qualified professional.
A new review paper just dropped in February 2026 in the journal ImmunoTargets and Therapy, and it’s worth breaking down for the community. The authors — researchers from Stanford, UC San Diego, and the University at Buffalo — are making a case that three conditions you’ve probably heard of: POTS, ME/CFS, and Long COVID, should be officially reclassified as neuroimmune disorders. That’s a big deal, and here’s why.
First, What Are These Three Conditions?
Let’s keep it simple:
POTS (Postural Orthostatic Tachycardia Syndrome) — when someone stands up, their heart rate spikes excessively (30+ beats per minute within 10 minutes of standing). It comes with dizziness, fatigue, brain fog, and exercise intolerance. It affects the autonomic nervous system — the part of your nervous system that runs things automatically, like heart rate, blood pressure, digestion, and breathing.
ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) — a complex condition characterized by severe, debilitating fatigue that doesn’t improve with rest, along with cognitive dysfunction, and a worsening of symptoms after physical or mental effort. It has historically been dismissed by mainstream medicine as psychological.
Long COVID — defined in this paper as a condition that occurs after SARS-CoV-2 infection and persists for at least 3 months, affecting one or more organ systems. POTS and ME/CFS are actually the two most common outcomes seen in Long COVID cases.
Why Does Reclassifying Them Matter?
For a long time, patients with these conditions were told their symptoms were psychological — anxiety, depression, or simply poor coping. The authors specifically call this out:
“Physicians were erroneously taught that since all routine diagnostic tests returned as ‘normal,’ then there should be no biological basis for the patient to remain sick.”
This is a huge problem. If doctors don’t believe the condition is real and biological, patients don’t get proper treatment. The authors draw a direct parallel to multiple sclerosis — a disease that was once dismissed as “hysterical paralysis” before it was properly understood as a neuroimmune disease. They’re arguing POTS, ME/CFS, and Long COVID are following the same pattern.
So What Is Actually Going On in the Body?
This is where it gets really interesting. The paper identifies several overlapping biological mechanisms across all three conditions. Let’s break each one down simply:
1. Autonomic Nervous System Dysfunction Your autonomic nervous system (ANS) controls everything your body does on autopilot — heart rate, blood pressure, digestion, temperature regulation. In all three of these conditions, this system is misfiring. The ANS is also deeply connected to the immune system through the vagus nerve, which the paper describes as “the critical component of the inflammatory reflex.” When the ANS is dysregulated, it can create a pro-inflammatory environment throughout the body.
2. Immune Dysregulation All three conditions show significant abnormalities in immune cell behavior. In ME/CFS specifically, researchers have found increases in certain B cells, exhausted T cells (T cells that have essentially burned out and can’t fight properly), and reduced NK cell function. NK cells are your body’s frontline virus-fighting cells. In Long COVID, there is evidence of chronically activated immune cells, hyperactivated mast cells, and elevated inflammatory markers like IL-6 and TNF — which are the same alarm signals discussed in the KPV post.
3. Autoimmunity This is one of the most significant findings. All three conditions show signs of the immune system attacking the body’s own tissues — specifically tissues involved in autonomic nervous system function. The paper notes that antibodies targeting adrenergic receptors (which regulate heart rate and blood pressure) have been found in patients with POTS, ME/CFS, and Long COVID. The same autoantibodies showing up across all three conditions is a major clue that they share underlying biology.
4. Mitochondrial Dysfunction Mitochondria are the energy factories of your cells. The paper identifies mitochondrial dysfunction as a likely contributor to the chronic, debilitating fatigue that defines all three conditions. When immune cells are chronically activated and exhausted, it puts enormous strain on mitochondrial function — which then impacts energy production at the cellular level across the entire body. One small study cited in the paper found that time-restricted eating over six months improved heart rate, energy levels, and mitochondrial function in POTS patients — an interesting finding worth watching.
5. Cerebral Hypoperfusion This simply means not enough blood is getting to the brain. The paper identifies this as a major mechanism in all three conditions, particularly at the brainstem — the region that controls heart rate, breathing, blood pressure, and digestion. Using advanced 7T MRI (a very high-powered imaging tool), researchers found structural abnormalities specifically at the dorsolateral medulla in Long COVID patients. This region is where the vagus nerve nuclei are located — connecting back to the immune and autonomic dysfunction points above.
6. Neuroinflammation Inflammation in the brain and nervous system. The paper highlights research showing microglial activation — microglia are the immune cells that live in the brain — in Long COVID patients, particularly in regions tied to cognition. The authors write that “microglial activation was found to be associated with the development of neurocognitive symptoms in Long COVID.” Brain fog, in other words, may have a measurable biological basis in neuroinflammation, not psychology.
How Are These Three Conditions Connected?
The paper makes the case that all three share the same core biological pathways — just triggered by different events. Long COVID is triggered by SARS-CoV-2 infection. ME/CFS is often triggered by other viral infections. POTS can be triggered by infection, pregnancy, trauma, or other events. But once triggered, the downstream biology — autoimmunity, immune exhaustion, neuroinflammation, autonomic dysfunction — looks remarkably similar across all three.
The authors summarize it well: these conditions demonstrate “overlapping pathophysiologies rooted in immune-mediated and neuroinflammatory pathways involving the interplay between the brain and the immune system.”
Why This Matters for the Research Space
The immune and inflammatory pathways discussed in this paper — NF-kB, cytokine dysregulation, mast cell activation, mitochondrial dysfunction — are the same pathways that many compounds in the research space interact with. Understanding the underlying biology of these conditions gives important context for why certain research directions around inflammation, immune modulation, and autonomic support are being explored with such interest.
This isn’t a treatment paper — it’s a classification and mechanistic review. But the mechanistic detail is dense and worth understanding, especially for anyone researching inflammation, immune dysregulation, or autonomic health.
Full citation: Blitshteyn S, Doherty TA, Steinman L. Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders. ImmunoTargets and Therapy. 2026;15. doi:10.2147/ITT.S581262
All content is for educational and research purposes only. Not medical advice. Not for human consumption. Always do your own research.

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