u/barweis

I was very much enthused by this article implying a viable modality applicable to treating LC19 or possibly acute covid as a speculation. The machinery involved in the inflammation can be sidetracked by this promising drug or its similars as a candidate. I went down the rabbit hole reading parts of the paper. There is mention of trial use in MS, diabetic related eye disease, Alzheimer's, etc., all tied together by the downstream effect of neurodegeneration triggered by the inflammasomes.

This fits in the framework of LC19 by virtue of the machinery of the inflammasome unleashing multiple pathologies of autoimmunity, immune dysfunction and their consequences. Preventing or tamping down the inflammasomes will reduce the resultant symptoms thus avoided.

https://www.nih.gov/news-events/news-releases/modified-hiv-drug-reverses-vision-loss-paralysis-multiple-sclerosis-model Modified HIV drug reverses vision loss and paralysis in multiple sclerosis model

Reference:

https://www.science.org/doi/epdf/10.1126/scitranslmed.aei2870

The nucleoside analog kamuvudine-9 shows protective and therapeutic efficacy in a mouse model of multiple sclerosis

The following two paragraphs aroused my curiosity for their mechanistic applications.:

"Previously, we found that nucleoside reverse transcriptase inhibitors (NRTIs), which are approved to treat HIV and hepatitis B virus(HBV) infections, also inhibit inflammasome activation independent of their antiretroviral activity (13). NRTIs block inflammasome activation and its associated damage in models of diabetes, diabetic retinopathy, aging, choroidal neovascularization, geographic atrophy and retinal detachment (14–20). NRTIs inhibit pathology driven by a dual NLRC4- NLRP3 inflammasome (19, 21, 22).

Although NRTIs inhibit inflammasome activation (13), they cause mitochondrial toxicity because of off-target inhibition of host DNA polymerase activity (23). This can result in serious adverse effects most notably lactic acidosis and potentially induction of viral resistance (24). Therefore, we developed alkylated derivatives of NRTIs known as kamuvudines that are inactive against reverse transcriptase or host DNA polymerase activity (13, 25). Because kamuvudines inhibit inflammasome activation without the off-target toxicity activities of NRTIs (13, 14, 19, 22), they are better translational drug candidates"

In short: an unused anti HIV drug combats inflammasome activation in aging, diabetes and its complications. OTOH its downside of inhibiting an enzyme needed for mitochondrial function allows the build up of lactic acid leading to a drop of pH and organ dysfunction and failure. To avoid this catastrophe, the chemical structure was modified and a new class known as kamuvudines were derived that lack the potential danger above.

The most studied inflammasome , NLRP3 in LC19, was strongly inhibited by kamuvudine 9 in the testing for its activities in the research into the mouse MS model. Its predecessors the NRTIs (used for HIV) reduced myelin loss and repaired it with restoration of neurological function in several HIV cohorts that developed MS .

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Society for Women's Health Research earned a 4/4 rating by Charity Navigator along with the Autoimmune Association. While not rated by Charity Navigator, the Global Autoimmune Institute is listed by SWHR as a resource. Both of their writings describing inflammasomes and autoimmunity are listed below the medical references.:

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My query for Google AI consisted of: "The role of inflammasome in long covid autoimmune disease in humans"

Response: "AI Overview

The inflammasome—specifically the NLRP3 inflammasome—acts as a persistent driver of innate immune overactivation, linking chronic Long COVID tissue inflammation to autoimmune-like pathology.

What is an Inflammasome?

• An inflammasome is a multi-protein package inside innate immune cells (like macrophages). [ My addition: The four component proteins of the assembly are produced when signals from the stimulus initiate their production. They remain in solution in the cytoplasm until a further signal activates their assembly into the actual inflammasome. They are products of innate immunity.]

• It detects cell stress, tissue damage, or lingering viral pieces.

• When activated, it turns on an enzyme called caspase-1.

How Inflammasomes Drive Long COVID Autoimmunity

• Persistent Cytokine Release: Activated caspase-1 cuts and releases powerful inflammation signals, specifically Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18).

• Loss of Self-Tolerance: Continuous high levels of these cytokines break down the body's immune regulation, leading immune cells to mistake healthy host tissues for foreign invaders (autoimmunity).

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12888595/ The NLRP3 inflammasome as a key pathway in the affective and chronic fatigue symptoms of Long COVID 9 (2026)

Conclusion: ..." The findings suggest that targeting the NLRP3 inflammasome strategically may be beneficial in addressing both the acute infectious phase of COVID-19 and the prolonged symptoms associated with Long COVID. Novel pharmacological agents are currently under development that specifically target the activation of NLRP3.".

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https://biospective.com/resources/what-is-an-inflammasome The Inflammasome – A Target for Therapeutic Development for Multiple Diseases (2025) An overview of inflammasomes, including their mechanisms of action, roles in diseases, and targeting for drug development.

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https://pmc.ncbi.nlm.nih.gov/articles/PMC8706865/ Inflammasomes and SARS-CoV-2 Infection (Dec 2025)

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https://pmc.ncbi.nlm.nih.gov/articles/PMC8348456/ Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2 (Jul 2021)

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https://pmc.ncbi.nlm.nih.gov/articles/PMC8233448/ The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies (Jun 2021)

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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.583373/full The Inflammasome in Times of COVID-19 (Oct 2020)

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https://autoimmune.org/blog/long-covid-autoimmune-disease/ Long COVID and Autoimmune Disease: How They’re Connected

https://www.autoimmuneinstitute.org/covid_timeline/persistent-inflammation-may-link-long-covid-to-autoimmune-disease/ Persistent Inflammation May Link Long COVID to Autoimmune Disease

https://swhr.org/office-of-autoimmune-disease-research-director-shares-whats-ahead-for-autoimmune-disease-innovation/ Office of Autoimmune Disease Research Director Shares What’s Ahead for Autoimmune Disease Innovation

Just for the record, in the aftermath of C19 as a one off:

"COVID-19 immunity may help protect against other bat coronaviruses

Study identifies links between virus host range and immune recognition

People who recovered from COVID-19 infection or were vaccinated against SARS-CoV-2 are more likely to have immunity to other closely related bat coronaviruses that could have the potential to threaten future human health.

In a joint study by The Pirbright Institute and King’s College London (KCL), scientists found bat coronaviruses most likely to infect a wide range of animal species are those most closely related to SARS-CoV-2 and most likely to be recognized by immunity generated through COVID-19 infection."

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Reference:

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003944 Breadth of ACE2 receptor usage predicts host range and antigenic relatedness across bat sarbecoviruses

"COVID-19–related hospitalization is associated with an increased risk of both hemorrhagic and ischemic stroke, with the greatest danger soon after infection, per a study published last week on the preprint server Research Square.

The study, conducted from March 2020 through May 2022, also suggested that being vaccinated for COVID-19 is associated with a lower likelihood of stroke. " (first two paragraphs)

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Reference:

https://www.researchsquare.com/article/rs-11101879/v1 (preprint)

SARS-CoV-2 severity and vaccination, pneumonia, and the risk of Stroke: A nationwide, nested case-control study

Registration window drop down on this page clicking on button on right side:

https://www.tickettailor.com/events/universityofedinburgh12/2155140

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https://www.actionforme.org.uk/wp-content/uploads/2026/06/PRIME-2026-Symposium-Preliminary-Program-v1-1.pdf

PRIME-2026-Symposium-Preliminary-Program-v1-1.pdf

DAY 2: Current Research: Objectives, Impact & Patient Involvement 9.00-9.10am Welcome (AfME) 9.10-9.30 PRIME PPI Research Involvement Hub – Sian Leary (AfME) 9.30-9.45 AfME Big Survey – Intro and Preliminary Findings – Katharine Cheston 9.45-10.25 AfME/PPI-led Workshop – 3 x breakout groups 10.25-10.40 Feedback from breakout sessions BREAK 11.15-11.35 Talk – Prof. Rob Wust 11.35-11.55 Rosetta Stone – Prof. Danny Altmann 11.55-12.15 DISCOVERME – Prof. David Price 12.15-12.35 Sequence ME & Long Covid – Prof. Chris Ponting 12.35-12.45 Closing Remarks, Poster Prizes, Feedback Forms, Plans for Symposium 2 LUNCH 12.45-2pm END OF DAY 2/SYMPOSIUM

This is a big development upcoming for large recruitment on a platform with encouraging results.

Reference:

https://www.medrxiv.org/content/10.64898/2026.09.22.26363331v1 (preprint) Worsening pre-existing health conditions in U.S. adults with Long COVID

Below is a further expansion of just a handful. The references elaborate their development from a unique progenitor cells lineage, a distinction only arrived at in 2018 from painstaking experiments. The functions of mast cells derive from the local environment of the resident population where they mature and differs from organ system to others.

Mast cells removed for expansion to larger populations for in vitro study do not display the characteristics of mast cells resident in the body unless modified by use of additional mediators. This is explained by the preceding concept (first paragraph).

FYI: Here is a short list of titles delving into the migration of immature mast cells from their origins to their their maturation in their final location. There are a few articles that go into excruciating detail regarding mechanisms of their roles in tissue repair and damage.

Some of their activities surprised me with a deeper understanding of the mast cell as an actor with dual roles in both innate and adaptive immunity. Though mast cell reactivity is primarily recognized with allergic phenomena, still they have other functions.

Their activity in the the extracellular matrix parenchyma and barriers (adjacent to basement membranes proximity to mucosa) is paramount working in tandem with the endothelial cells in the turnover of the matrisome - the substance of the ECM. EDS derives from pathological processes involving proteases produced by mast cells.

In addition the mast cells are vital agents with the neurological and vascular systems and others. Mast cells usually reside along with neural and vascular structures. For example, in the vascular endothelium mast cells extend cell processes across the vessel wall to interact with immune mediators. These fascinating details will produce a greater appreciation for the often overlooked mast cell.

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https://pubmed.ncbi.nlm.nih.gov/18538784/ Comparison of short term in vitro cultured human mast cells from different progenitors - Peripheral blood-derived progenitors generate highly mature and functional mast cells

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https://pubmed.ncbi.nlm.nih.gov/36752151/ Mast cell ontogeny - From fetal development to life‐long health and disease

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https://pubmed.ncbi.nlm.nih.gov/32929378/ Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts

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https://pubmed.ncbi.nlm.nih.gov/39223427/ Mechanisms of assembly and remodelling of the extracellular matrix

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https://pubmed.ncbi.nlm.nih.gov/8648190/ Interactions of immature human mast cells with extracellular matrix - expression of specific adhesion receptors and their role in cell binding to matrix proteins

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https://pmc.ncbi.nlm.nih.gov/articles/PMC4701915/ Mast Cell: A Multi-Functional Master Cell

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10885734/ Mast cells must stick

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https://link.springer.com/article/10.1007/s12016-019-08729-w A Review of the Contribution of Mast Cells in Wound Healing - Involved Molecular and Cellular Mechanisms

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https://www.cell.com/immunity/pdf/S1074-7613%2824%2900531-4.pdf Beyond classical immunity - mast cells as signal converters between tissues and neurons

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https://pmc.ncbi.nlm.nih.gov/articles/PMC3576928/ Perivascular mast cells dynamically probe cutaneous blood vessels to capture IgE

"The findings suggest that chronic fatigue syndrome (ME/CFS), long COVID, posttraumatic stress disorder (PTSD), rheumatoid arthritis, and multiple sclerosis (MS) may share underlying biological mechanisms."

..."the broader interpretation the researchers draw from the analysis."

“Rather than viewing long Covid, ME/CFS, PTSD, rheumatoid arthritis and multiple sclerosis as entirely separate disorders, we now think they may be different manifestations of disturbed biological networks operating throughout the body. In that scenario, chronic exhaustion is not simply a symptom. It is the visible consequence of a deeper systems failure affecting immune function, metabolism, and stress-response pathways.”

“This study offers a framework for understanding how different triggers can converge to cause the exact same profound clinical exhaustion.”(excerpts)

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Reference:

https://link.springer.com/article/10.1186/s12967-026-08874-9

Beyond genes: EpiSwitch® and Orion platform-powered 3D genome architecture biomarkers reveal shared biology across ME-CFS, long COVID, PTSD, rheumatoid arthritis, and multiple sclerosis

Is LC19 responsible/associated with the development of EDS by disrupting various feed -back /-forward loops of normal physiology? How? Before or after the symptom reveals itself?

We can ask the same or similar question for the exposure of any of the multiple sequelae of LC19.

https://adelaide.edu.au/about/news/2026/new-clues-link-long-covid-and-pots/

"Dizziness, fatigue, brain fog and a racing heart. They’re commonly associated with Long COVID, but new Adelaide University research suggests that for some people, these symptoms may also be indications of Postural orthostatic tachycardia syndrome (POTS), a debilitating and difficult-to-diagnose condition.

Conducted in partnership with SAHMRI, the study compared heart rate changes, symptoms and immune profiles among people with POTS, Long COVID and healthy participants, finding that almost two-thirds (62.5%) of the Long COVID participants also met the diagnostic criteria for POTS." (First two paragaphs from the article.)

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Reference:

https://www.ahajournals.org/doi/10.1161/JAHA.125.048615 Comparative Analysis of Circulating Cytokines and Adrenergic Autoantibodies in Postural Orthostatic Tachycardia Syndrome, Postacute Sequelae of SARS‐CoV‐2, and Healthy Controls

Much ado about little. The genus has multiple species and within them multiple varieties.

For starters each of the distinct plant lineages possess individual and shared attributes. Their use depends on the tradition as they may greatly differ with the locale they are found in. Moreover, historical experience defines their unique applications by locale, so it is a risky venture to generalize their properties accounting for their dispersed sources. (My interpretation of the use of a natural products which is a melange of myriad components which vary considerably in concentrations)

https://pmc.ncbi.nlm.nih.gov/articles/PMC5983702/ Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology

The clickbait headline belies the actual state of progress that it remains in its infancy of use in conventional medicine not ready for prime time. The studies are still being done in vitro not yet having transferred over to live platforms.

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Reference:

https://www.nature.com/articles/s41598-025-25217-8 Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins

A few researchers are breaking some scattered silos of highly detailed narrowly focused studies finding patterns. LC19 premature senescence is a singular (?) phenomenon of the broader process described here.

Another well studied entity, the mast cell, varies significantly in its response to signaling depending on the particular niche in which it resides. Mast cell responses vary according to their location whether at the barrier layer or deep in the parenchyma. This phenomenon is known as mast cell heterogeneity. By studying patterns some sensitive points of reactions are exposed which are reviewed for clinical intervention. Perhaps later, these may be treated in the medical system by altering the disease process.

https://pubmed.ncbi.nlm.nih.gov/39529115/ p16Ink4a-induced senescence in cultured mast cells as a model for ageing reveals significant morphological and functional changes

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.70186 A Prominent Pro-Inflammatory Phenotype Is Observed in Replication and Stress-Induced Senescent Mast Cells

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Reference: https://link.springer.com/article/10.1186/s12915-026-02672-x Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis

Summary: Scientists discovered that aging cells can use malfunctioning mitochondria to unlock inflammatory genes and keep the immune system stuck in a prolonged state of alert. Blocking one part of this process reduced inflammation and improved healthy aging in mice, suggesting a promising new strategy for fighting age-related decline.

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By reducing the 'zombie cells' of lc19 we lower the burden of premature senescence and associated chronic inflammation.

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Original paper:

https://www.nature.com/articles/s41586-026-10791-2 Mitochondrial metabolism and epigenetic crosstalk drive SASP

Summary: Scientists have uncovered a natural braking system that helps the immune system switch off inflammation and prevent harmful immune cells from building up. Boosting this pathway in people reduced inflammation-related immune changes and sped up pain relief, pointing toward potential new treatments for chronic inflammatory diseases.

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We are highlighting another possible point of entry into eventually reducing the inflammation of LC19.

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Original article:

https://www.nature.com/articles/s41467-025-67961-5 Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans

Reduced clearance of metabolic waste is implicated in disturbed cognition in various scenarios of neurodegeneration.

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Reference link:

https://www.science.org/doi/10.1126/sciadv.aeb0404

MR-AIV reveals in vivo brain-wide fluid flow with physics-informed AI

..."However, nearly 70% of adults aged 65 and up remain unvaccinated against COVID-19, putting them at higher risk of serious illness. According to Sanofi, many within this age group remain unvaccinated due to concerns about side effects and uncertainty about evolving health guidance.

“Concerns about potential vaccine side effects can be a barrier to vaccination for older adults, who don’t want disruption in their daily lives and hobbies,” Sanofi’s head of marketing and commercial strategy, U.S. vaccines Sriram Jambunathan explained. “By teaming up with USA Pickleball on ‘Serve Up Protection,’ we’re educating older adults that Nuvaxovid can help provide powerful protection against COVID-19 with manageable side effects.”

This is not a commercial for any product. The message is based on the facts that I am less reactive to the immunization than to the five sessions I had initially with the Moderna. I have no stake or reward for endorsing any product. This is just my own experience with the injections and the plain statement from the manufacturer.