Delivered-To: tjphuhs@gmail.com Received: by 2002:a05:6000:10c9:b0:43d:781a:c227 with SMTP id b9csp606750wrx; Mon, 13 Apr 2026 08:17:17 -0700 (PDT) X-Received: by 2002:ac8:590a:0:b0:509:3cd:b22f with SMTP id d75a77b69052e-50dd5af20e4mr204645541cf.23.1776093436734; Mon, 13 Apr 2026 08:17:16 -0700 (PDT) ARC-Seal: i=1; a=rsa-sha256; t=1776093436; cv=none; d=google.com; s=arc-20240605; b=UQrz1jVc/aoHjL2i3nSGYbab8i25/XfGek2y9TJj9C6K7gHoIvwrGN33wyEjD/nCT1 883yeXOXUysEMA/DPA2suB0x+fT9d6d1B5d2D8U8SFJJMYLmo+VUPTG+Kl2ZE5DQVzm4 TFG7JKQJMZ4ZkXigfvAgb8XQA3IhThvdX6OaPASC7kZlt/KMSwfgXxb0KL1MNI1Di7sY BDvnbKpLC6mhnEcQb838j14MOc8WrVHBgui2O0bl6vV2deVwjH9cnFRYC0anIHH1Kzy0 rq9QArD7STjw9OSUbcelAOu8ovnqoZ8+CI0t7SoK+uepjDTjBxDBQ6dv0Xx++xUUB9AF 0sdw== ARC-Message-Signature: i=1; a=rsa-sha256; c=relaxed/relaxed; d=google.com; s=arc-20240605; h=list-unsubscribe-post:list-unsubscribe:list-post:list-id :list-archive:list-url:list-owner:reply-to:in-reply-to:references :sender:feedback-id:date:message-id:to:from:subject:mime-version :dkim-signature:dkim-signature; bh=+CrUaDdGqQDHyfWcFbwmn71gjTlUVUDR+NyeTDlPd+g=; fh=9zP21OW67FFZD2VV42mGudo540Qp4aalMWxJB5kMYug=; b=Ti/7XrWCod7flHcPtSy+7i8cDQZq35g083ll/FfqknE9bRNiCbQCgXEcuNZaMqq+rk ab6J4eZ05dkIDwnxW+CLZ4qSj1uINF9zwvY3ACmcHTRhiOBCT/q+CgSIIR/ELGaXSClX z1gTO17s7ERf/7CencW2YM3c4P4rwyCu6hkuaZ8QvdPzI8b0mPpZ01jK8z+WH++sDdQd kdeHNmOeSZusrQRUd66f+dwzbtdtzJsa61q5MvuzjdSx7CqTkQ5eB8L6cda8IwQnLSEI r7C2vFjPCYx+5W+Lbd34pEQHvI3Vh7x9iM2Z+7mqs4SQKKmkVljux7pOyVXVUfhBGTAo Hnbg==; dara=google.com ARC-Authentication-Results: i=1; mx.google.com; dkim=pass header.i=@mg2.substack.com header.s=mailo header.b=gxO19Yki; dkim=pass header.i=@mailgun.org header.s=mg header.b="kfv/KYnx"; spf=pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.47 as permitted sender) smtp.mailfrom="bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com Return-Path: Received: from v547.v5375b7fa.use4.send.mailgun.net (v547.v5375b7fa.use4.send.mailgun.net. [159.112.244.47]) by mx.google.com with UTF8SMTPS id d75a77b69052e-50dd564cccdsi136430411cf.200.2026.04.13.08.17.16 for (version=TLS1_2 cipher=ECDHE-ECDSA-AES128-GCM-SHA256 bits=128/128); Mon, 13 Apr 2026 08:17:16 -0700 (PDT) Received-SPF: pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.47 as permitted sender) client-ip=159.112.244.47; Authentication-Results: mx.google.com; dkim=pass header.i=@mg2.substack.com header.s=mailo header.b=gxO19Yki; dkim=pass header.i=@mailgun.org header.s=mg header.b="kfv/KYnx"; spf=pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.47 as permitted sender) smtp.mailfrom="bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mg2.substack.com; q=dns/txt; s=mailo; t=1776093436; x=1776100636; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=+CrUaDdGqQDHyfWcFbwmn71gjTlUVUDR+NyeTDlPd+g=; b=gxO19Ykin9Y4kFaPJwtUPWAfU5YeTXc1yXNH3fGPAgSzHpHG8PDFsll8Y224vImCYjy4wMYfxlAIMXZVgEZgTfc8kl/qfPOlT3Ice9FEHoqgqmyIlM0jfrK7jfOJ04LI1OdDX5s5dkN5p1Dj6SrjIo6LEh6Aieh57ImOrs6RHlA= DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mailgun.org; q=dns/txt; s=mg; t=1776093436; x=1776100636; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=+CrUaDdGqQDHyfWcFbwmn71gjTlUVUDR+NyeTDlPd+g=; b=kfv/KYnxOVKS8gnfdJOSWtQ27vBguTlDPK8wSG0tzCbfwLiiPWbZl9FVEXst0XFdK1bRM147B2lfoBL1LsyzKMlo7lkp/HztcwLzX7+Immqw6jL5zJhNwx+Je8Ym33MwUXftDKtP0k9A/ZnLzEeK1h28E36fxFAJFEJ7I/skY+w= X-Mailgun-Sid: WyIxODZiYSIsInRqcGh1aHNAZ21haWwuY29tIiwiNGQxODU4Il0= X-Feedback-Id: postmaster@mg2.substack.com:post:5a78b6d5cd16820001f2a9d4:mailgun Received: by 58994dcbe968cc723dc8f5c3fd633ab85864e9bd708a990670d83d7d3fcc02cf with HTTP id 69dd08fc30bb068c5bcdb48b; Mon, 13 Apr 2026 15:17:16 GMT X-Mailgun-Sending-Ip: 159.112.244.47 Mime-Version: 1.0 Content-Type: multipart/alternative; boundary="d070cfd3d2ade67626ad6530021fafa83b586eae4baf322d81c391aff1a4" Subject: =?UTF-8?q?POTS,_ME/CFS,_and_Long_COVID_Are_Being_Reclassified_=E2=80=94_H?= =?UTF-8?q?ere's_What_That_Means?= From: Derek from Research Radar To: tjphuhs@gmail.com X-Mailgun-Tag: post X-Mailgun-Track-Clicks: false Message-Id: <20260413151706.3.d14dadb29c61c1c0@mg2.substack.com> Date: Mon, 13 Apr 2026 15:17:06 +0000 Feedback-Id: post-194082541:cat-post:pub-3365367:substack Sender: Derek from Research Radar References: In-Reply-To: Reply-To: Derek from Research Radar List-Owner: List-Url: List-Archive: List-Id: List-Post: List-Unsubscribe: List-Unsubscribe-Post: List-Unsubscribe=One-Click X-Mailgun-Variables: {"category": "post", "email_generated_at": "1776093436035", "is_freemail": "true", "post_audience": "everyone", "post_id": "194082541", "post_type": "newsletter", "pub_community_enabled": "true", "publication_id": "3365367", "subdomain": "derekpruski", "user_id": "273622398"} --d070cfd3d2ade67626ad6530021fafa83b586eae4baf322d81c391aff1a4 Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: quoted-printable 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 p= urposes only. This is not medical advice. Always do your own research and c= onsult a qualified professional. A new review paper just dropped in February 2026 in the journal ImmunoTarge= ts and Therapy, and it=E2=80=99s worth breaking down for the community. The= authors =E2=80=94 researchers from Stanford, UC San Diego, and the Univers= ity at Buffalo =E2=80=94 are making a case that three conditions you=E2=80= =99ve probably heard of: POTS, ME/CFS, and Long COVID, should be officially= reclassified as neuroimmune disorders. That=E2=80=99s a big deal, and here= =E2=80=99s why. First, What Are These Three Conditions? Let=E2=80=99s keep it simple: POTS (Postural Orthostatic Tachycardia Syndrome) =E2=80=94 when someone sta= nds up, their heart rate spikes excessively (30+ beats per minute within 10= minutes of standing). It comes with dizziness, fatigue, brain fog, and exe= rcise intolerance. It affects the autonomic nervous system =E2=80=94 the pa= rt of your nervous system that runs things automatically, like heart rate, = blood pressure, digestion, and breathing. ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) =E2=80=94 a com= plex condition characterized by severe, debilitating fatigue that doesn=E2= =80=99t improve with rest, along with cognitive dysfunction, and a worsenin= g of symptoms after physical or mental effort. It has historically been dis= missed by mainstream medicine as psychological. Long COVID =E2=80=94 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 outcom= es seen in Long COVID cases. Why Does Reclassifying Them Matter? For a long time, patients with these conditions were told their symptoms we= re psychological =E2=80=94 anxiety, depression, or simply poor coping. The = authors specifically call this out: =E2=80=9CPhysicians were erroneously taught that since all routine diagnost= ic tests returned as =E2=80=98normal,=E2=80=99 then there should be no biol= ogical basis for the patient to remain sick.=E2=80=9D This is a huge problem. If doctors don=E2=80=99t believe the condition is r= eal and biological, patients don=E2=80=99t get proper treatment. The author= s draw a direct parallel to multiple sclerosis =E2=80=94 a disease that was= once dismissed as =E2=80=9Chysterical paralysis=E2=80=9D before it was pro= perly understood as a neuroimmune disease. They=E2=80=99re 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 over= lapping biological mechanisms across all three conditions. Let=E2=80=99s br= eak each one down simply: 1. Autonomic Nervous System Dysfunction Your autonomic nervous system (ANS)= controls everything your body does on autopilot =E2=80=94 heart rate, bloo= d pressure, digestion, temperature regulation. In all three of these condit= ions, this system is misfiring. The ANS is also deeply connected to the imm= une system through the vagus nerve, which the paper describes as =E2=80=9Ct= he critical component of the inflammatory reflex.=E2=80=9D When the ANS is = dysregulated, it can create a pro-inflammatory environment throughout the b= ody. 2. Immune Dysregulation All three conditions show significant abnormalities= in immune cell behavior. In ME/CFS specifically, researchers have found in= creases in certain B cells, exhausted T cells (T cells that have essentiall= y burned out and can=E2=80=99t fight properly), and reduced NK cell functio= n. NK cells are your body=E2=80=99s frontline virus-fighting cells. In Long= COVID, there is evidence of chronically activated immune cells, hyperactiv= ated mast cells, and elevated inflammatory markers like IL-6 and TNF =E2=80= =94 which are the same alarm signals discussed in the KPV post. 3. Autoimmunity This is one of the most significant findings. All three con= ditions show signs of the immune system attacking the body=E2=80=99s own ti= ssues =E2=80=94 specifically tissues involved in autonomic nervous system f= unction. The paper notes that antibodies targeting adrenergic receptors (wh= ich regulate heart rate and blood pressure) have been found in patients wit= h POTS, ME/CFS, and Long COVID. The same autoantibodies showing up across a= ll 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 contribut= or 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 =E2=80=94 which then impacts energy produ= ction at the cellular level across the entire body. One small study cited i= n the paper found that time-restricted eating over six months improved hear= t rate, energy levels, and mitochondrial function in POTS patients =E2=80= =94 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 cond= itions, particularly at the brainstem =E2=80=94 the region that controls he= art rate, breathing, blood pressure, and digestion. Using advanced 7T MRI (= a very high-powered imaging tool), researchers found structural abnormaliti= es specifically at the dorsolateral medulla in Long COVID patients. This re= gion is where the vagus nerve nuclei are located =E2=80=94 connecting back = to the immune and autonomic dysfunction points above. 6. Neuroinflammation Inflammation in the brain and nervous system. The pape= r highlights research showing microglial activation =E2=80=94 microglia are= the immune cells that live in the brain =E2=80=94 in Long COVID patients, = particularly in regions tied to cognition. The authors write that =E2=80=9C= microglial activation was found to be associated with the development of ne= urocognitive symptoms in Long COVID.=E2=80=9D Brain fog, in other words, ma= y 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 path= ways =E2=80=94 just triggered by different events. Long COVID is triggered = by SARS-CoV-2 infection. ME/CFS is often triggered by other viral infection= s. POTS can be triggered by infection, pregnancy, trauma, or other events. = But once triggered, the downstream biology =E2=80=94 autoimmunity, immune e= xhaustion, neuroinflammation, autonomic dysfunction =E2=80=94 looks remarka= bly similar across all three. The authors summarize it well: these conditions demonstrate =E2=80=9Coverla= pping pathophysiologies rooted in immune-mediated and neuroinflammatory pat= hways involving the interplay between the brain and the immune system.=E2= =80=9D Why This Matters for the Research Space The immune and inflammatory pathways discussed in this paper =E2=80=94 NF-k= B, cytokine dysregulation, mast cell activation, mitochondrial dysfunction = =E2=80=94 are the same pathways that many compounds in the research space i= nteract with. Understanding the underlying biology of these conditions give= s important context for why certain research directions around inflammation= , immune modulation, and autonomic support are being explored with such int= erest. This isn=E2=80=99t a treatment paper =E2=80=94 it=E2=80=99s a classificatio= n and mechanistic review. But the mechanistic detail is dense and worth und= erstanding, especially for anyone researching inflammation, immune dysregul= ation, or autonomic health. Full citation: Blitshteyn S, Doherty TA, Steinman L. Postural Orthostatic T= achycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and= Long COVID as Neuroimmune Disorders. ImmunoTargets and Therapy. 2026;15. d= oi:10.2147/ITT.S581262 All content is for educational and research purposes only. Not medical advi= ce. Not for human consumption. Always do your own research. Unsubscribe https://substack.com/redirect/2/eyJlIjoiaHR0cHM6Ly9kZXJla3BydXN= raS5zdWJzdGFjay5jb20vYWN0aW9uL2Rpc2FibGVfZW1haWw_dG9rZW49ZXlKMWMyVnlYMmxrSW= pveU56TTJNakl6T1Rnc0luQnZjM1JmYVdRaU9qRTVOREE0TWpVME1Td2lhV0YwSWpveE56YzJNR= Gt6TkRNMkxDSmxlSEFpT2pFNE1EYzJNamswTXpZc0ltbHpjeUk2SW5CMVlpMHpNelkxTXpZM0lp= d2ljM1ZpSWpvaVpHbHpZV0pzWlY5bGJXRnBiQ0o5LlFGVF9pbXNmMTRCTndFa2tKT01HTjhhQXl= FcFp0bG1obWR6OFVrYWNuTXciLCJwIjoxOTQwODI1NDEsInMiOjMzNjUzNjcsImYiOnRydWUsIn= UiOjI3MzYyMjM5OCwiaWF0IjoxNzc2MDkzNDM2LCJleHAiOjIwOTE2Njk0MzYsImlzcyI6InB1Y= i0wIiwic3ViIjoibGluay1yZWRpcmVjdCJ9.yyhmX-TPRrchdh79DoLO4ldEBaQSpsmsmol3VHI= Beu4? --d070cfd3d2ade67626ad6530021fafa83b586eae4baf322d81c391aff1a4 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable = POTS, ME/CFS, and Long COVID Are Being Reclassified — Here's What Tha= t Means3D""
Before diving in: all content shared here is for edu= cational and research purposes only.
͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­
=
Forwarded this email? Subscribe here for more
 

Before diving in: all conte= nt shared here is for educational and research purposes only. This is not m= edical advice. Always do your own research and consult a qualified professi= onal.

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 conditi= ons 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.

3D""

First, What Are These Three Conditions?<= /strong>

Let’s keep it simple:

POTS (Postural Orthostatic Tachycardia Syndrome) — w= hen someone stands up, their heart rate spikes excessively (30+ beats per m= inute within 10 minutes of standing). It comes with dizziness, fatigue, bra= in fog, and exercise intolerance. It affects the autonomic nervous system &= #8212; 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, debilitat= ing fatigue that doesn’t improve with rest, along with cognitive dysf= unction, and a worsening of symptoms after physical or mental effort. It ha= s historically been dismissed by mainstream medicine as psychological.

Long COVID — defined in thi= s 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 sy= mptoms were psychological — anxiety, depression, or simply poor copin= g. The authors specifically call this out:

“Physician= s were erroneously taught that since all routine diagnostic tests returned = as ‘normal,’ then there should be no biological basis for the p= atient to remain sick.”

This is a huge problem. If do= ctors don’t believe the condition is real and biological, patients do= n’t get proper treatment. The authors draw a direct parallel to multi= ple sclerosis — a disease that was once dismissed as “hysterica= l paralysis” before it was properly understood as a neuroimmune disea= se. They’re arguing POTS, ME/CFS, and Long COVID are following the sa= me pattern.

So What Is Actually Going On in the Body= ?

This is where it gets really interesting. The pa= per identifies several overlapping biological mechanisms across all three c= onditions. Let’s break each one down simply:

= 1. Autonomic Nervous System Dysfunction Your autonomic nervo= us system (ANS) controls everything your body does on autopilot — hea= rt rate, blood pressure, digestion, temperature regulation. In all three of= these conditions, this system is misfiring. The ANS is also deeply connect= ed to the immune system through the vagus nerve, which the paper describes = as “the critical component of the inflammatory reflex.” When th= e ANS is dysregulated, it can create a pro-inflammatory environment through= out the body.

2. Immune Dysregulation All three conditions show significant abnormalities in immune cell= behavior. In ME/CFS specifically, researchers have found increases in cert= ain B cells, exhausted T cells (T cells that have essentially burned out an= d can’t fight properly), and reduced NK cell function. NK cells are y= our body’s frontline virus-fighting cells. In Long COVID, there is ev= idence of chronically activated immune cells, hyperactivated mast cells, an= d elevated inflammatory markers like IL-6 and TNF — which are the sam= e alarm signals discussed in the KPV post.

3= =2E Autoimmunity This is= one of the most significant findings.= All three conditions show signs of the immune system attacking the body= 217;s own tissues — specifically tissues involved in autonomic nervou= s system function. The paper notes that antibodies targeting adrenergic rec= eptors (which regulate heart rate and blood pressure) have been found in pa= tients with POTS, ME/CFS, and Long COVID. The same autoantibodies showing u= p across all three conditions is a major clue that they share underlying bi= ology.

4. Mitochondrial Dysfunction= Mitochondria are the energy factories of your cells. The paper ident= ifies mitochondrial dysfunction as a likely contributor to the chronic, deb= ilitating fatigue that defines all three conditions. When immune cells are = chronically activated and exhausted, it puts enormous strain on mitochondri= al function — which then impacts energy production at the cellular le= vel across the entire body. One small study cited in the paper found that t= ime-restricted eating over six months improved heart rate, energy levels, a= nd mitochondrial function in POTS patients — an interesting finding w= orth 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, partic= ularly at the brainstem — the region that controls heart rate, breath= ing, blood pressure, and digestion. Using advanced 7T MRI (a very high-powe= red imaging tool), researchers found structural abnormalities specifically = at the dorsolateral medulla in Long COVID patients. This region is where th= e vagus nerve nuclei are located — connecting back to the immune and = autonomic dysfunction points above.

6. Neuro= inflammation Inflammation in the brain and nervous system. T= he paper highlights research showing microglial activation — microgli= a are the immune cells that live in the brain — in Long COVID patient= s, particularly in regions tied to cognition. The authors write that “= ;microglial activation was found to be associated with the development of n= eurocognitive 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 C= OVID is triggered by SARS-CoV-2 infection. ME/CFS is often triggered by oth= er viral infections. POTS can be triggered by infection, pregnancy, trauma,= or other events. But once triggered, the downstream biology — autoim= munity, immune exhaustion, neuroinflammation, autonomic dysfunction —= looks remarkably similar across all three.

The authors sum= marize it well: these conditions demonstrate “overlapping pathophysio= logies rooted in immune-mediated and neuroinflammatory pathways involving t= he interplay between the brain and the immune system.”

Why This Matters for the Research Space

T= he immune and inflammatory pathways discussed in this paper — NF-kB, = cytokine dysregulation, mast cell activation, mitochondrial dysfunction = 212; are the same pathways that many compounds in the research space intera= ct with. Understanding the underlying biology of these conditions gives imp= ortant context for why certain research directions around inflammation, imm= une modulation, and autonomic support are being explored with such interest= =2E

This isn’t a treatment paper — it’s a c= lassification and mechanistic review. But the mechanistic detail is dense a= nd worth understanding, especially for anyone researching inflammation, imm= une dysregulation, or autonomic health.

Full citation: Blitsh= teyn S, Doherty TA, Steinman L. Postural Orthostatic Tachycardia Syndrome, = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroi= mmune Disorders. ImmunoTargets and Therapy. 2026;15. doi:10.2147/ITT.S58126= 2

All content is for educational and research purposes only= =2E Not medical advice. Not for human c= onsumption. Always do your own researc= h.

Upgrade to paid<= /a>

You're currently a= free subscriber to Research R= adar. For the full experience, upgrade your subscrip= tion.

Upgrade to paid

 
=
<= /table>
3D""Share
 
 
=
= Like
3D""Comment=
3D""= Restack=
 

© 2026 Derek Pruski
548 Market Street PMB 72296, San Francisco, CA 9410= 4
Unsubscribe=

3D"Start

3D""3D"" --d070cfd3d2ade67626ad6530021fafa83b586eae4baf322d81c391aff1a4--