Margot

[Margot @AleSceni]

Palestinian Refugees Deserve to Return Home. Jews Should Understand. https://t.co/Ey6GTfVoj7

[Lamine Yamal Fans 🇪🇸 @Ros10101]

No words

[Harry Spoelstra @HarrySpoelstra]

T-cell exhaustion in COVID-19: what do we know?

🔥A very interesting literature review from Panama, an eye-opener for many, worth your time, especially for those minimisers😡! #LEONARDI_EFFECT

➡️T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors.

➡️In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID.

➡️Mechanisms of T-Cell Exhaustion in SARSCoV2:
1. Hallmarks: Upregulated PD-1/TIM-3/LAG-3, reduced IFN-γ/TNF-α/IL-2, impaired proliferation/cytotoxicity, and paradoxical hyperactivation.
2. Drivers: TOX/NR4A transcription, cytokine storm (IL-6/IL-10/TNF-α), metabolic defects (glycolysis/ROS), epigenetic repression (H3K27me3/DNA methylation).
3. Dynamics: "Transient" in mild cases, persistent in severe, fuelling immunopathogenesis. Reinfections?

Exhaustion arises from chronic antigen/inflammation, reprogramming T cells for dysfunction and poor viral clearance.

➡️Key Points on Clinical Implications of T-Cell Exhaustion in COVID-19:
1. Disease Severity & Progression, Elevated PD-1/TIM-3 on CD8+ T cells correlates with severe outcomes, lymphopenia, and impaired IFN-γ/granzyme B, predictive for mortality, "transient" in mild cases, persistent in severe.
2. Long COVID (PASC): Up to 30% affected, features exhausted CD8+PD-1+TOX+ and CD4+CTLA-4+ T cells, reduced IL-2/proliferation, linked to fatigue, brain fog, impairs vaccine responses and REINFECTION protection.
3. Opportunistic Infections: Increases herpesvirus (CMV/EBV) reactivation and nosocomial risks (aspergillosis), tied to poor IFN-γ responses, prolonging hospitalization/mortality.

T-cell exhaustion drives acute severity, Long COVID persistence, and secondary infections via immune dysregulation, urging exhaustion metrics for triage and targeted therapies.

➡️Long COVID and T-Cell Dysfunction:
1. Prevalence & Definition: Affects ~30% post-COVID, WHO: symptoms ≥3 months from onset, unexplained by alternatives.
2. Symptoms: Fatigue, dyspnea, brain fog, myalgia, no single mechanism, but T-cell exhaustion central.
3. Markers: Expanded PD-1+TOX+ CD8+ and CTLA-4+ CD4+ T cells, low IL-2/proliferation, coexists with CRP/IL-6 inflammation.
4. Implications: Oral PASC risks damage, dysbiosis, autoimmunity, impairs vaccine/memory responses, REINFECTION protection.

Long COVID (PASC) can persist for more than 12 months, driven by exhausted T cells in a feedforward inflammation loop, targeting therapies for reversal and enhanced immunity.

➡️Therapeutic and Immunization Strategies to Overcome T-Cell Exhaustion:
1. Checkpoint Inhibitors: Anti-PD-1/TIGIT block inhibitory signals, boosting IFN-γ/proliferation, preclinical restoration, but risks cytokine storms.
2. Cytokine Modulation: IL-7 expands lymphocytes (phase 2 success), IL-6/IL-10 blockade mixed, curcumin/resveratrol dampen inflammation.
3. Plasma Exchange: Clears mediators, accelerates immune recovery, lowers mortality in ARDS trials.
4. Metabolic Reprogramming: Metformin/mTOR inhibitors restore glycolysis/mitochondria, retrospective benefits.
5. Epigenetic Modulation: HDAC/DNA inhibitors reverse chromatin locks, preclinical reactivation.
6. Next-Gen Vaccines: Heterologous/multi-epitope/mucosal designs promote exhaustion-resistant memory T-cells.

Emerging therapies may be able to reverse exhaustion via blockade, modulation, and reprogramming, enhancing outcomes in severe COVID-19 and Long COVID

➡️Conclusion:
T-cell exhaustion in SARS-CoV-2, a multifactorial immunopathology, drives acute severity and Long COVID via upregulated inhibitory receptors, impaired cytokines, metabolic/epigenetic defects. Heterogeneous across stages/tissues, it impairs vaccine responses and memory. Reversing it is key to survival, sequelae mitigation, and variant immunity in the “endemic” era. #LEONARDI_EFFECT

https://t.co/y0mFLTpUnT

[Massimo peace ☮️🕊️ 🇵🇸🇨🇺 @_MaxFree_]

Testimonianza della Dott.ssa Noonan, chirurgo canadese tornata da Gaza

Ha visto bambini con arti frantumati, ospedali distrutti e dottori uccisi mentre cercavano di salvare vite.

"Ho visto sofferenze inimmaginabili", "Nemmeno i medici sono stati risparmiati".

[TRT World @trtworld]

Wafaa Hamad, a Palestinian girl who lost her entire family in an Israeli air strike on their home in western Gaza on September 3, 2024, has died after a year of suffering due to the lack of medicine and care under Israel’s blockade.

She lost her right leg and suffered severe injuries and internal damage that led to a coma

[Israel Exposed @xIsraelExposedx]

Jewish Doctor Stanley Plotkin testifies under oath that he used orphans, babies, and people living under colonial rule as test subjects for vaccines.

[Margot @AleSceni]

@FinoF45877 @fanpage Sei un pezzo di merda

[Monica Dall'Asta 🏴🇵🇸 @moni_dall]

"Prelievo sistematico di organi sotto il controllo israeliano."

[il manifesto @ilmanifesto]

La legge di bilancio redistribuisce al contrario: dai poveri verso chi ha di più. A certificarlo sono l’Istat, Bankitalia e l’Ufficio parlamentare di bilancio che nelle audizioni al senato bocciano la manovra. Irpef: 408 euro all’anno ai dirigenti, 23 agli operai
#7novembre

[AJ Leonardi, MBBS, PhD, MPH @fitterhappierAJ]

Epidemiological studies are post-hoc

Why would I not anticipate what would happen by understanding the basic science of T cell sloughing, hyperactivation, exhaustion, and apoptosis?

All of which are basic science

Do you believe epidemiology is science and immunology is not?

[Margot @AleSceni]

@Maumol Credibile😅

[Gimmoriso' 🇵🇸 @fawollo13]

Brunetta si è aumentato lo stipendio al CNEL, da 250 a 310mila euro all'anno. E con lui tutti i suoi dirigenti, facendo raddoppiare la spesa per le retribuzioni del CNEL. Lo stesso Brunetta fortemente contrario, come tutto il governo, al salario minimo di 9 euro l'ora. Schifosi

[Margot @AleSceni]

@putino E che notizia e?

[World Affairs @World_Affairs11]

BREAKING:

Mamdani Zohran says his first aim is to arrest Netanyahu if he enters New York city.

[Sulaiman Ahmed @ShaykhSulaiman]

ISRAEL BOOBY TRAPED CHILDREN'S TOYS IN GAZA WITH EXPLOSIVES

Pure evil.

[mostro ✊🏼  🇵🇸 @avantibionda]

È stata arrestata lei perché ha fatto uscire il video con gli stupri e le torture, mica quelli che hanno fatto quella roba sotto.
Funziona così in quella che parenzo, cerno&co garantiscono sia una democraticissima democrazia.

Yifat Tomer-Yerushalmi
Sde Teiman

[Elio Vito 🇮🇹🇪🇺🇺🇸🏳️‍🌈🌍 @elio_vito]

Il successo di Mamdani a New York conferma che NON si vince al centro.

[Rula Jebreal @rulajebreal]

Netanyahu da detto: “Questa è una lotta tra i figli della luce e i figli delle tenebre, tra l'umanità e la legge della giungla”.
Merz: “Israele fa il lavoro sporco per l’Occidente.”
Gli stupratori israeliana che hanno violentato un medico palestinese davanti alle telecamere tengono una conferenza stampa per affermare che rimangono liberi.

[Rabbi Moishe Indig @MoishIndig]

Heartiest congratulations and Mazel Tov to New York City Mayor-elect Zohran Mamdani. We are proud to endorse you and look forward to your leadership, vision, and collaboration for the betterment of our community and all New Yorkers

[Francesca Albanese, UN Special Rapporteur oPt @FranceskAlbs]

In Palestine there is NO ceasefire, NO peace, only destruction and the violence of ethnic cleansing.
Watching world leaders play “let’s pretend” with the light-heartedness of 4th graders playing Lego is sickening. We will all pay for their complicity & the insecurity it is sowing