Manuel Ruiz-Pablos

manruipa.substack.comThe Antiviral Question We Can No Longer Ignore: Viral Persistence, EBV, and the Immune Trap Behind Long COVID and ME/CFSNew evidence of viral persistence and immune dysfunction raises a crucial question: could antivirals help treat Long COVID and ME/CFS, or might we need more?

🔴 Could antivirals help in Long COVID and ME/CFS—and why might they not be enough? New studies connect viral persistence, EBV and T-cell dysfunction. I explore the evidence and the possible role of autoimmunity. manruipa.substack.com/p/the-antivi...

manruipa.substack.comDifferent Infections, the Same Immune Trap? New Evidence on Long COVID, EBV, and T Cell ExhaustionNew evidence links persistent T cell activation, immune exhaustion, and EBV in long COVID, supporting an immunopathological model we proposed in 2023.

🔴Could different infections trigger the same immune dysfunction? New long COVID findings reveal T cell activation, exhaustion-like dysfunction and altered EBV responses. Could antivirals help end this cycle? I explore the evidence and our research since 2021 manruipa.substack.com/p/different-...

Manuel Ruiz-Pablos reposted

manruipa.substack.comGinseng, cortisol and the HPA axis: an overlooked connection in ME/CFS and Long COVIDWhat SARS, autoimmune disease and decades of neuroendocrine research can teach us about hypocortisolism — and why ginsenosides deserve a closer look

Could altered cortisol signalling contribute to fatigue in ME/CFS and Long COVID? A 2026 meta-analysis found lower cortisol availability and altered HPA-axis regulation in ME/CFS. After SARS, hypocortisolism affected 24/61 survivors. I explore this and ginseng manruipa.substack.com/p/ginseng-co...

manruipa.substack.comMelatonin Is More Than a Sleep Hormone — What the Evidence Actually SaysSleep, circadian timing, mitochondria, red light, Long COVID, ME/CFS and the recent cardiovascular controversy

If you have Long COVID or ME/CFS and struggle with unrefreshing sleep, insomnia or disrupted circadian rhythms, melatonin may be more interesting than it seems. I reviewed what we know about dose, timing, mitochondria, inflammation and safety. manruipa.substack.com/p/melatonin-... #LongCOVID #MECFS

manruipa.substack.comCan the Innate Immune System Remember? How Trained Immunity Could Change Vaccination, Genetics and Our Understanding of Chronic DiseaseCan infections leave a lasting imprint on our immune system? Exploring trained immunity and its potential implications for Long COVID, ME/CFS and future vaccines.

Can an infection change how our immune system responds years later? In my new article, I explore trained immunity, future vaccines and potential links to Long COVID and ME/CFS. Subscribe for free! 🩵 manruipa.substack.com/p/can-the-in...

Manuel Ruiz-Pablos reposted

manruipa.substack.comAutism, congenital infections and autoimmunity: what does the science actually tell us?From genetics and TORCH infections to maternal autoantibodies, cerebral folate deficiency and the possible lessons from ME/CFS and Long COVID

Could congenital infections influence autism? A new study of 3.6 million people raises questions about genetics, immunity and brain development. My latest article explores the evidence and possible links with ME/CFS and Long COVID. 🩵 manruipa.substack.com/p/autism-con...

Manuel Ruiz-Pablos reposted

manruipa.substack.comNAC, glutamate and the brain: why is such an old mucolytic drug attracting interest in depression, multiple sclerosis, autoimmune disease, ME/CFS and Long COVID?N-acetylcysteine (NAC) is an old mucolytic with a surprisingly modern story: it sits at the crossroads of glutamate, glutathione, mitochondria, oxidative stress and immune regulation.

21 Sept

Why is NAC attracting interest in MS, autoimmunity, ME/CFS and Long COVID? My Substack explores how glutamate, glutathione, mitochondria, astrocytes and immune metabolism may connect. 🔗 manruipa.substack.com/p/nac-glutam... #MECFS #LongCOVID

21 Sept

Manuel Ruiz-Pablos reposted

manruipa.substack.comWhat if EBV reactivation helps trigger autoimmune relapses?New evidence from multiple sclerosis is connecting viral reactivation, HLA genetics, B-cell biology and loss of immune tolerance

18 Sept

New evidence suggests EBV reactivation may precede MS relapses, linking viral persistence, B cells, HLA and autoimmunity. This may also matter for subsets of ME/CFS and Long COVID with impaired EBV control. Full article: manruipa.substack.com/p/what-if-eb... #EBV #MECFS #LongCOVID

18 Sept

manruipa.substack.comBezisterim in Long COVID: a new approach to fatigue, brain fog and PEMA new Phase 2 trial suggests that targeting inflammatory signalling in the brain may help fatigue, cognitive dysfunction and post-exertional malaise in some people with Long COVID

15 Sept

🔴 Fatigue, brain fog & PEM in Long COVID: a new Phase 2 trial with bezisterim points again to neuroinflammation and the ERK–NF-κB–TNF-α axis. I review the results, limitations and how it compares with LDN/metformin: manruipa.substack.com/p/bezisterim... #LongCOVID #MECFS

Manuel Ruiz-Pablos reposted

manruipa.substack.comAntihistamines Beyond Allergy: Mast Cells, Long COVID, ME/CFS, Autoimmunity and Viral PersistenceWhat if histamine is not the disease itself, but one layer of a much larger immune process?

12 Sept

🔴 What if histamine is not the disease itself, but one layer of a larger immune process? Mast cells, Long COVID, ME/CFS, autoimmunity and viral persistence — and why treatment may need to target different physiological layers. manruipa.substack.com/p/antihistam... #LongCOVID #MECFS

manruipa.substack.comNicotine patches beyond smoking cessation: what could they actually be doing in Long COVID and ME/CFS?The cholinergic hypothesis is biologically interesting, but the evidence is far more complex than the idea that nicotine simply “displaces Spike” from a receptor

14 Sept

Nicotine patches in Long COVID/ME/CFS: what does the evidence actually show? I review nAChRs, PET findings, dysautonomia, Mestinon and autoimmunity. manruipa.substack.com/p/nicotine-p... #LongCOVID #MECFS

12 Sept

manruipa.substack.comWhere Does Fatigue Really Come From?What Long COVID, ME/CFS, autoimmune diseases, fibromyalgia, cancer and post-infectious syndromes may teach us about the shared biology of fatigue

11 Sept

Why can Long COVID, ME/CFS, lupus, MS, fibromyalgia, IBD or Lyme disease cause similar fatigue? My article explores immune, autonomic, neuroimmune & metabolic pathways — and why we may need biomarkers of mechanism, not just fatigue scores. manruipa.substack.com/p/where-does... #LongCOVID #MECFS

substack.comManuel Ruiz-Pablos (@manruipa)New article about Mestinon (pyridostigmine) in Long COVID and ME/CFS. I look at why it may make physiological sense in some patients with dysautonomia, low preload or impaired autonomic compensation,...

9 Sept

🔴New article on Mestinon in Long COVID and ME/CFS. Why might it help some patients with dysautonomia, low preload or impaired autonomic compensation, while doing little for others? I also look at GPCR autoantibodies, POTS and alternative treatments. substack.com/@manruipa/no... #LongCOVID #MECFS

substack.comLong COVID Did Not Come Out of Nowhere: A Century of Post-Infectious IllnessFrom the Russian flu and the 1918 influenza pandemic to EBV, Q fever, SARS, Ebola and ME/CFS — what history can teach us about why some people never fully recover after infection

9 Sept

🔴 Long COVID didn’t come out of nowhere. From the Russian flu and 1918 influenza to EBV, Q fever, SARS and Ebola, post-infectious illness has a much longer history. What can that history teach us about Long COVID & ME/CFS? substack.com/@manruipa/no... #LongCOVID #MECFS

manruipa.substack.comLow-Dose Naltrexone in Long COVID and ME/CFS: Neuroinflammation, TRPM3 and the Search for the Right PatientWhy LDN may make biological sense in some patients — and why comparing it with metformin reveals a bigger problem in how we study post-infectious disease

8 Sept

🔴New on Substack: a deeper look at low-dose naltrexone in Long COVID and ME/CFS — from neuroinflammation and TLR4 to TRPM3, Ca²⁺ signaling, clinical evidence, metformin and why patient subgroups may matter. manruipa.substack.com/p/low-dose-n...

substack.comAre persistent pathogens an overlooked part of healthy aging?Why immunosenescence, viral reactivation and chronic immune stimulation may deserve a place in the longevity conversation

6 Sept

🔴A few of you suggested I start posting my long threads as articles too, so I finally opened a Substack 😅 I’m completely new there, but I’ll be uploading article versions of my threads for those who prefer that format or don’t use X. substack.com/@manruipa/no...

substack.comMetformin Beyond Diabetes: Why It May Matter in Long COVID and ME/CFSFrom immunometabolism and viral persistence to oxidative stress, endothelial dysfunction and patient selection

5 Sept

For those of you asking where you can read my posts if you don’t have X, I’m going to start publishing article versions of my threads on Substack as well 😊 That way, you’ll be able to read them in full without needing an X account: substack.com/@manruipa/no...

🔴🚩🧵 What if part of severe Long COVID and ME/CFS is not “mysterious” — but untreated, potentially reversible HPA-axis damage? We already saw this after SARS-1. It happened again with SARS-CoV-2. And almost no one is screening for it. Some of the worst symptoms may be preventable.

⏳ When will early endocrine intervention become standard of care? Because delayed recognition may turn reversible dysfunction into permanent damage. And that is avoidable.

🔁 If you know patients with Long COVID or ME/CFS — or clinicians treating them — please share this. Early endocrine evaluation could prevent years of avoidable deterioration in a subset of patients. Screening is simple. Permanent damage is not. Let’s stop missing what is testable.

How many patients are told “your labs are normal” while sitting at the lower edge of cortisol reserve? 7️⃣The bigger picture This is not about one virus It is a recurring pattern: Viral infection → inflammatory/autoimmune pituitary involvement → secondary hypocortisolism → chronic symptom persistence

The literature is there. The precedent is there. The replication is there. Yet it remains under-recognized. Final thought We are not proposing something new. We are pointing out something that already happened once — and is happening again.

If secondary adrenal insufficiency is not recognized early: • Chronic hypocortisolism persists • Inflammation worsens • Autonomic instability increases • Recovery becomes harder Early detection could prevent long-term endocrine damage.

6️⃣ The uncomfortable question If we already knew this from SARS-1… And similar findings are now documented in SARS-CoV-2… Why is early endocrine screening not standard in Long COVID? Morning cortisol alone is not enough. Dynamic testing (ACTH stimulation, ITT) is often required.

In other words: SARS-1 mechanism documented (2005) ↓ Mechanistic extrapolation to SARS-CoV-2 (our review, July 2024) ↓ Clinical confirmation in SARS-CoV-2 (August 2024) History repeating itself.

5️⃣ Why does this matter? HPA-axis damage is not trivial. The adrenal glands and pituitary have: ⚠️ Very low regenerative capacity ⚠️ Slow cellular turnover ⚠️ Limited repair once chronic fibrosis sets in

frontiersin.orgFrontiers | Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitisMyalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology...

– inflammatory hypophysitis – or autoimmune processes targeting hypothalamus/pituitary Again, review here: www.frontiersin.org/journals/imm... Because this pattern had already happened.

ec.bioscientifica.comec.bioscientifica.com

4️⃣ And then what happened? One month after our review was published… A new SARS-CoV-2 paper reported pituitary involvement and secondary adrenal insufficiency in COVID-19. ec.bioscientifica.com/view/journal...

Post-mortem data (Wei et al.) also showed reduced corticotroph staining. This was not psychosomatic. It was endocrine.

3️⃣ What did we write in 2024? In our review, we argued that: • SARS-CoV-2 shares high genetic similarity with SARS-CoV • Therefore, similar HPA-axis vulnerability is biologically plausible • Hypocortisolism in Long COVID may reflect: – direct viral injury

2️⃣What happened with the first SARS (2003)? After the original SARS-CoV outbreak, Leow et al. (2005) showed that ~40% of SARS survivors developed secondary adrenal insufficiency, likely due to pituitary involvement.

onlinelibrary.wiley.comHypocortisolism in survivors of severe acute respiratory syndrome (SARS)Objective Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we so...

Importantly: • It was often reversible • Early recognition mattered • It strongly suggested inflammatory pituitary damage Original study: onlinelibrary.wiley.com/doi/10.1111/...

Read this thread — and consider discussing testing with your doctor. 👇 1️⃣ HPA axis damage in Long COVID and ME/CFS is not new. We’ve seen this before. In July 2024, in our review, we discussed something many still overlook:

👉 Hypocortisolism in ME/CFS and Long COVID may result from direct infection or immune-mediated damage of the HPA axis (hypothalamus–pituitary–adrenal). Our review: www.frontiersin.org/journals/imm...

Manuel Ruiz-Pablos reposted