Definizione molecolare di fragilita' al COVID-19
Coronavirus: un approccio biochimico alla prevenzione e cura

Author: Gianpiero Pescarmona
Date: 26/10/2020

Description

La letteratura e la circolare ministeriale del 01/04/2020 danno della fragilita' una descrizione vaga e piena di dubbi.
Non pare sufficiente il riferimento al medico competente, la cui reale competenza e formazione non viene definita.

I dati dell'ISS ci dicono di quali patologie soffrivano i pazienti morti, ma non le basi molecolari delle patologie.
Dati al 13 gennaio 2021
La mortalità totale per COVID-19 è l'unico parametro espresso in maniera certa. Invece le % degli infetti totali sono solo stime sulla base di campioni imperfetti.
La crescita esponenziale di cui si sente spesso parlare non ha senso, perche' si applica a una popolazione infinita.

la curva attesa non puo' che essere una logistica che inizia come esponenziale, ma rallenta man mano che il numero degli infettati cresce e quello degli infettabili diminuisce

How to linearize the logistic

Proviamo a darne una descrizione meno aleatoria basata sulle basi molecolari dei sintomi

Se noi prendiamo le condizioni (vecchiaia, ipertensione, obesità eccetera) usualmente associate alle forme più gravi di COVID-19 vediamo che hanno alcune caratteristiche metaboliche comuni

Fattore di rischioDHEACortisoloGSHVit DBMR
Etàbassoaltobassobassobasso
Diabetebassoaltobassobassobasso
Ipertensionebassoaltobassobasso?
Obesita'bassoaltobassobassobasso
Diuretici??-alto--?
Farmaci--bassobasso?
Inquinamento Atmosferico--bassobasso?
Paracetamolo--basso-?
Clorochina--basso-?
Cortisonici-alto--?
Ibuprofen----?

Il BMR (metabolismo basale) misura la quantità di Ossigeno trasformata in CO2 dal metabolismo cellulare a riposo su un periodo di 30 minuti. Tale misura dipende dallo stato ormonale, dall'età, dalla dieta, dall'esercizio fisico.

Il Glutatione (GSH) è composto da 3 aminoacidi e svolge molte funzioni. La sua concentrazione nelle cellule è pari a quella del glucoso nel sangue (ca. 5 mM)

Letteratura 2020 su GSH

Letteratura 2020 su Vitamina D

Il basso livello di GSH si accompagna a modificazioni dei gruppi -SH delle proteine

Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration, 2019 fulltext

Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration, 2020

glyphosate+GSH

Il meccanismo con cui si manifesta l'eccesso di risposta infiammatoria in tali pazienti e' riassunto nella figura seguente

Il sistema Renina-Angiotensina-Aldosterone

La gran parte delle forme gravi di COVID-19 rientra in questo schema, ma molti sono preoccupati delle morti in soggetti giovani, in assenza di queste patologie.

La preoccupazione nasce dal pensiero: sarò anch'io in quel 3% (approssimato)?

Quali sono le caratteristiche genetiche, di solito misconosciute, che possono rendermi fragile?
Se assumiamo che l'eccesso di cortisolo, secondario ad una scarsa respirazione e produzione di ATP a livello cerebrale, sia la causa prevalente di COVID severo possiamo identificare alcuni difetti genetici che si accompagnano a ridotta respirazione:

Questi fattori di rischio genetici possono essere facilmente identificati con due semplici esami di sangue:

  • Colesterolo e colesterolo HDL
  • Bilirubina frazionata

Conclusione preliminare

L'uso di uno schema come quello sommariamente delineato, e passibile di infiniti ampliamenti, mi sembra degno di essere discusso e completato, e potrebbe essere utile per portare su un piano di ragionevolezza l'attuale approccio alla prevenzione

Altri approcci al problema

Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study 20 10 2020

Protective factors

high BMR

covid-19+and+cystic+fibrosis

Vaccini: quanto davvero ci proteggeranno?

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data 04 01 2021

Protezione da altre patologie

Case Report: Hyperbilirubinemia in Gilbert Syndrome Attenuates Covid-19-Induced Metabolic Disturbances, 2021

  • Gilbert syndrome (GS) is a liver disorder characterized by non-hemolytic unconjugated hyperbilirubinemia. On the other hand, Coronavirus disease 2019 (Covid-19) is a recent viral infectious disease presented as clusters of pneumonia, triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Little is known on the association between SARS-CoV-2 and GS, despite different studies have recently stated a link between hyperbilirubinemia and SARS-CoV-2 severity. In this case-report study we described a 47-year-old man, a known case of GS since the age of 4, presented to the emergency department with fever (39.8°C), dry cough, dyspnea, headache, myalgia, sweating and jaundice diagnosed with Covid-19-induced pneumonia. Interestingly, GS patient exhibited a rapid clinical recovery and short hospital stay compared to other SARS-CoV-2 positive patient, seeming that hyperbilirubinemia may exert a protective effect of against Covid-19 induced-cardiometabolic disturbances. Data obtained here underlines that the higher resistance against Covid-19 evidenced by the GS patient seems to be due to the antioxidant, anti-inflammatory, and antiviral effects of unconjugated bilirubin.

Metformin

COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin, 19 02 2021

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability.

Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated.

Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.

Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.

Metformin reduces cortisol production in diabetic patients (personal observation)

Leukotrienes receptors inhibitors

Montelukast Drug May Improve COVID-19 Prognosis: A Review of Evidence, 2020

  • With the lack of effective therapy, chemoprevention and vaccination, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Interestingly, montelukast, a drug usually used in asthma, may be proposed as a potential adjuvant therapy in COVID-19. The aim of the present article was to review the properties of montelukast that could be beneficial in COVID-19. Ten experimentally supported properties were retrieved, either related to SARS-CoV-2 (antiviral properties, prevention of endotheliitis and of neurological disorders linked to SARS-CoV-2), and/or related to the host (improvement of atherogenic vascular inflammation, limitation of the ischemia/reperfusion phenomenon, improvement of respiratory symptoms), and/or related to serious COVID-19 outcomes (limitation of the cytokine storm, mitigation of acute respiratory distress syndrome), and/or related to tissue sequelae (antioxidant properties, anti-fibrosis effects). Based on gathered theoretical evidence, we argue that montelukast should be further tested to prevent and treat COVID-19 outcomes.
Comments
2021-09-09T10:49:31 - Gianpiero Pescarmona

Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis

2010

Abstract
Rapid activation of adrenal steroid release plays a pivotal role in an organism's first line of defense during sepsis. Adrenal gland function is often suppressed in critically ill patients and negatively impacts the overall survival rate. Increasingly, experimental and clinical evidence suggests that Toll-like receptors (TLRs), components of the innate immune system, play a key role in the mediation of systemic responses to invading pathogens during sepsis. In the present study, we aimed to elucidate the effect of TLR2, TLR4 and CD14 upregulation on adrenocortical cell steroidogenesis. We found that TLR4 and CD14 but not TLR2 overexpression in NCI-H295R cells inhibited basal and acute cortisol and aldosterone production. This effect could be partially explained by reduced expression of enzymes involved in the synthesis of latter steroids--CYP11B1 and CYP11B2. Together, these data suggest that TLR upregulation in the steroid producing cells may be involved in the adrenal gland dysfunction during sepsis.

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