Resia Pretorius

We welcome you to join us on Friday, March 13 at 1 pm ET (US) for a Research Roundtable with @resiapretorius of @StellenboschUni @LivUni, @dbkell of @LivUni, @jfvaughnmd09 of MedHelp, and @CenterJill of @CUMedicalSchool! They'll be discussing Hypercoagulability, Clotting and Microclotting, and Blood Issues in ME/CFS and Long Covid Registration is free and open to the public! 🧵See this thread for the event registration link and research our panelists have authored:

Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system 🔥Again, EXCELLENT work from @resiapretorius et. al 💪👇 ➡️This review article proposes a combining mechanistic hypothesis for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID as post-viral syndromes. ➡️The hypothesis synthesizes existing evidence(The facts= fig) without new primary data, emphasizing the endothelium as the core driver. ➡️Main points : 1. Acute viral infections (e.g., SARS-CoV-2, influenza A, EBV, HHV-6) trigger direct or indirect endothelial cell dysfunction and senescence in tissues like the blood-brain barrier, cerebral arteries, gastrointestinal tract, and skeletal muscle. 2. Senescent endothelial cells exhibit a senescence-associated secretory phenotype (SASP) that is proinflammatory (e.g., IL-6, TNF-α), pro-oxidative, procoagulant (e.g., PAI-1, TF, vWF), vasoconstrictive (e.g., elevated ET-1, reduced NO), and impairs tissue repair, leading to multisystem symptoms including reduced cerebral blood flow, perfusion deficits, post-exertional malaise (PEM), fatigue, cognitive issues, and gut disturbances. 3. Immune abnormalities/DYSFUNCTION (e.g, reduced NK cell cytotoxicity, T-cell exhaustion, complement deficits, macrophage impairment) prevent clearance of senescent cells, often via HLA-E evasion, creating a bidirectional vicious cycle: → Senescence-Associated Secretory Phenotype (also called the senescence messaging secretome or SMS)(SASP) promotes immune dysfunction, while dysfunctional immunity sustains chronic endothelial senescence beyond the acute infection. 4. This framework explains the shared chronicity, heterogeneity, and vascular origins of both conditions, with elevated SASP markers (e.g., ET-1, VCAM-1, ICAM-1) observed in patients. 5. The clear implications include developing endothelial-specific biomarkers (e.g., microRNA-126) and senotherapeutics (Therapeutic agents/strategies that specifically target cellular senescence) to clear senescent cells and alleviate symptoms, potentially revolutionizing diagnosis and treatment. ‼️So, both ME/CFS and long COVID are fundamentally driven and chronically maintained by PERSISTENT ENDOTHELIAL CELL SENESCENCE, triggered, by acute viral infection and prolonged by IMMUNE DYSFUNCTION, which causes multisystem inflammation, impaired tissue perfusion (especially in the brain), and the full spectrum of devastating symptoms including PEM and profound fatigue. 🤔VERY INTERESTING, now looking forward to future research that builds on this model by examining how SARS-CoV-2 reinfections, viral variants, and vaccination status affect endothelial senescence induction, SASP persistence, impaired immune clearance, and chronic disease progression. nature.com/articles/s4141…