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The success of a pleiotropic  therapy against  COVID-19

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Clinical Reports of the Milan School of Medicine. 2022; 1


           

The success of a translational integrated therapy against COVID-19

 

DOI: 10.13140/RG.2.2.15071.12964

 

Giuseppe R.Brera


Abstract

A sixty-year-old unvaccinated woman, a great smoker, with a determinate temperament and basic trust, and a previous history of breast cancer with a swab positive diagnosis of COVID-19 developed a
temperature of 40 degrees, with headache and cough, an indicator of a high cytokine storm. She received an integrated therapy based on translational medicine structured on well-studied natural molecules
integrated with Nimesulide and Doxiciclin. The woman recovered from the severe COVID-19 syndrome in four days and joined the swab negativity in 10 days from the beginning of symptoms returning to work on the 11th day.

 

Mass vaccination was the first time used to prevent a pandemic, but with experimental mRNA and vectorial vaccines dangerous at the epigenetic-genetic level,[1] [2] [3] [4] induced production of variants of concern evading immunity [5]  and induced mass immunosuppression increasing vulnerability to cancer, neurodegenerative disease, cardiovascular diseases,  immune thrombocytopenia, Bell's palsy, liver disease. These sera have been offered to the market worldwide with unreliable clinical research methods, [6]  produce a high risk of mortality for cardiovascular diseases under 39 yo people [7]  and met in a minority of people, physicians, and investigators a healthy diffidence and prudency to vaccinate people and themselves. The epigenetic earthquake caused by mRNA vaccines, although an object of controversy about its form,[8]  found epidemiological and clinical evidence that confirm the theoretical assumptions [9] [10]  with many unpublished records. These sera should have requested larger samples and an extended study over time. The fundamental epistemological error at the origin of the SARS-COV 2 pandemic has been the lack of adoption in public health of the paradigm change of medical science and medicine, Person-Centered Medicine. This omission hampered an effective and cheap alternative allowing people, primarily in countries with insufficient financial resources, to prevent and care for viral and bacterial infections opening the doors to an immense business for BIG-PHARMA increasing political powers, based on illiteracy.  To date, the obsolete and wrong deterministic-mechanistic paradigm used to cope with the pandemic implementing only biotechnology and profit is "Pathogen-infection- mortality risk" and not the right indeterministic multidimensional one:" Pathogen-anti-pathogen allostasis = antiviral metabolic allostasis and immunity stimulation -resilience- recovery." [11] According to the Person-centered medicine primary prevention and therapy paradigm, we are ethically, epistemologically, and scientifically obliged to address preventive and clinical efforts to improve life quality and psycho-biological resources to prevent and care for diseases and not to adopt problem-centered epistemology, which enhances only the disease-centered stock market only with a reductionist biotechnological approach. The World Health Charter should be adopted worldwide. [12]   

Antiviral drugs and monoclonal antibodies are developed through fragmented research methods and show dangerous adverse effects, while there are in nature pleiotropic, powerful and cheap molecules that, without adverse effects, act contemporary at a biochemical and immunological level showing a great preventive action and effective therapy. The road map for prevention and treatment should be based on the physiology revolution of "allostasis" (Sterling and Heyer), to date unknown to most physicians and investigators. [13] Substituting the obsolete concept of "Homeostasis" (Cannon).

The antiviral targets of prevention and a successful therapy anti-SARS-COV two variants of concern (VOC) should be addressed to use pleiotropic molecules to increase resilience to the infection blocking it (Table 1).

One of us recently introduced the COVID-19 person-centered prevention and early treatment paradigm based on the epistemological concept of antiviral allostasis and immunostimulation, identifying the relativity of the SARS-COV 2 entry into cells and reviewing the pleiotropic antiviral targets of naturals molecules spread worldwide. .[14] [15], a strategy inspired by Person-Centered Medicine (PCM), the current paradigm of Medical Science, not well known yet. [16]  At the clinical level, PCM acts through the Person-Centered Clinical Method that allows the physician to identify the subjective-biological-environmental patient's resources for improving the person's lifestyle quality. [17]

In fact, a clinical case is not a probabilistic event of a natural law mechanistic and deterministic alterations [18] not to be considered independent of the person's possibilities for the best personal being. This approach is founded on the person-centered concept of health as" The choice of the best possibilities for being the best human person" [1] related to the interaction among the spiritual- psycho-neuro-endocrine, immunity systems, [19]  determining the allostatic changes of the individual epigenetic transmission. The COVID-19 prevention and early treatment inducing an antiviral allostasis and immunostimulation is entrusted to the person's natural immune system through the metabolic antiviral allostatic changes and can be reinforced by a resource-centered healthy lifestyle and powerful antiviral substances that act as pleiotropic natural epigenetic programmers at immunity -biochemical level. Nutrition quality and its possibility is part of healthy or bad life quality and education to health, which cannot be separated by the ontologic human freedom to interpret experience and choose among experience possibilities and build reality., making health relative to the individual interpretation quality of experience possibilities.[20]

Curcumin, Aloe, Lactoferrin, Epigallocatechin, Beta-glucans Sphingosine, Lysozyme, Mannan binding lectins, and Quercetin are natural molecules with a well-documented powerful pleiotropic antiviral allostasis and immunostimulant actions. [21]  Vit A and C are immunostimulants, and VIT D metabolites, cathelicidin, have direct virucide properties. [22] Lysozyme has a barrier effect in viral infections, is an immunostimulant but suppresses TNF-α and IL-6 production by macrophages.and hydrolyzes gram-positive bacterial walls. [23]Nimesulide has potent anti-inflammatory and antiviral properties, with well-studied significant therapeutic successes [24], and its association with maltodextrins also results in immunostimulation. [25] [26]   Doxiciclin also has antibacterial and antiviral properties. [27] Conversely, the antipyretic paracetamol suggested and defended by the Italian Health Ministry to treat early COVID is dangerous because it promotes coagulation and has no anti-inflammatory effects, and this illiterate health policy was responsible for thousands of deaths. [28]

A sixty years old unvaccinated woman, a great smoker, with a determinate temperament, good basic trust, and a previous history of breast cancer with a positive swab diagnosis of COVID-19 developed a temperature of 40 degrees, with headache and cough, an indicator of a high cytokine storm. Paracetamol administration, prescribed by phone by an illiterate emergency unit, according to the correspondent Italian health ministry indications, was suspended. An integrated pleiotropic therapy with drugs was prescribed with the resolution of COVID-19 syndrome in four days and the swab negativity in 10 days. The woman started to work on the 11th day of the pleiotropic therapy. (Table 2)

A pleiotropic person-centered oriented therapy is more effective than a fragmentized molecular one built on the imperant obsolete and wrong mechanistic paradigm of medical science. Many cheap natural and synthesis pleiotropic molecules offer the opportunity for effective prevention and therapy (Table 2) and allow joining at the same time, the anti-SARS-COV 2 targets extended to other communicable,-like influenza virus- and non-communicable diseases, like cancer, which shares with the first infection phase allostatic homologies. At the prevention level, the effectiveness of a pleiotropic activity of natural substances confers more protection than experimental mRNA vaccines that, after 120 days, are waning and in a paradoxical way, increase the risk of infections in vaccinated people confirming the epigenetic-induced immunosuppressive action,[29] and the absence of the B-cell memory.

Moreover, mRNA experimental vaccines show dangerousness caused by genotoxic and immunosuppressive effects, based on the silencing of microRNA and DNA gene promoters, through methylation and vectorial vaccines hybridizing DNA resulting in a vulnerability to autoimmunity. mRNA vaccines produce only circulating IGG and less IGA, waning in a short time, are inactive against VOC, and do not generate Memory B cells in lungs[30] with a high rate of life-threatening adverse effects.  Cells' methylation induces an increased risk of cancer.  [31] [32]  In vaccinated oncologic patients, there is an increase in infections, admissions to hospitals, and deaths. [33] [34]Monoclonal antibodies and antiviral drugs have many serious adverse effects, only induce fragmented therapeutical actions, and are expensive, while pleiotropic prevention and therapy join different antiviral targets simultaneously. (Table 1). The availability of pleiotropic natural substances worldwide and their low costs offer great possibilities for SARS-COV prevention and therapy in developing countries. Moreover, there is the impossibility of vaccinating the entire world. Antiviral allostasis and preventive immuno-stimulation, the pleiotropic strategy in therapy open new possibilities for self-care and health education by adopting the new paradigm of person-centered prevention, an alternative to future mass vaccination strategies with experimental vaccines, and a profit-centered stock market of disease.

 

 


 

Clinical Reports of the Milan School of Medicine. 2022; 1

 

Table 1

                                  Pleiotropic targets against SARS-COV 2 and variants of concern

 

1.               Inhibition of the virus binding to receptors (barrier effect);

2.               change of the Receptor Binding Domain

3.               inhibition of proteases cleaving the virus and blocking its entry into the cell

4.               prevention of NK and CD8 inhibition

5.               Increase of cytotoxic function of NK and LAK

6.               Immunostimulation          

7.               inactivation by viruses of the P53 gene and its reactivation;

8.               inhibition of replication

9.               prevention of  the critical anergy after the seventh day of the disease shared by patients with atherosclerosis -based comorbidities;

10.           creation and or induction of natural and or (A) humoral  adaptive immunity(B)

11.           prevention and inhibition of the virus induced viral allostatic metabolism and activation of antiviral allostasis

12.           prevention of cytokine storm-induced lung inflammation and in oral, nasal mucosae, and upper respiratory ways;

13.           plasma alkalinization

14.            Epigenetic programming (demethylation)

15.           Virus opsonization

 

 

©Giuseppe R.Brera 2022


Clinical Reports of the Milan School of Medicine. 2022; 1

 

 

Table 2

Posology in the clinical case treatment

 

 Substance-molecule

  Posology

Pleiotropic action of nutraceutics

 (table 1)

  Curcumin

Curcumin 500 mg x2

5’Inhalation of turmeric powder (10 g- two teaspoons)

 vapors from a solution with 100 ml of water at a boiled temperature

 1,2,4,7,8,9,11,12,14

Aloe extract

50 ml x 2

1,3,6,11

Lactoferrin

200 mg x 2 before meals

1,4,5,6,8,10

Epigallocatechin

Infusion of green tea (40°) four glasses per day ( 800 ml )

1,3,6.8,9.11,14

Resveratrol

1000 mg x 2 before meals

1,6,8,9,11,12,14

Sphingosine

 Beta-

Glucans

Lactobacilli

Kefir milk 200 ml x 3

SPH 1,12

BG   10

LB   6,12

Melatonin

5 mg before sleeping

6,9,11,12

Vit D

10.000 U ( 7 days) after 1000

1,2,9,11,12,14

Vit, C

500 mg

6,9,11,12,14

Vit A

5000 U

4,6,9,10,11,12,14

Nimesulide and maltodextrins

400 mg x 2

1,6 ,9,12

Doxiciclin

100 mg x1 (first dose 200 mg)

3.14 and antipoptois

Quercetin (foods)

 

    Foods rich of quercetin

1,3,6,8,11,12,14

Mannan binding lectins

    Foods rich of MBL

 1,2,3,7,9,12,15

           

Table 1 Posology of the integrated pleiotropic therapy-

( Doses are referred one-two time a day , morning ad evening)

 

©Giuseppe R.Brera 2022




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[12]  Università Ambrosiana. “ Medical Science and health Paradigm Change” G.R. Brera ed.. Proceedings of the Conference Milan 13-14-15 October 2017. Milan; Università Ambrosiana: 2018 Internet www.health paradigm change.it

 

 

 

[13]  Sterling P., Eyer J. Allostasis: a new paradigm to explain arousal pathology. In: Fischer S Reason J. editors. Handbook of Life Sciences, cognition, and Hea[7] Robinson, E.G., Fernald R., Clayton D. Genes and Social Behavior.Science 2008;322:896-lth. New York 1988: J.Wiley and sons;p. 629-649

 

 

[14]  Brera G.R. SARS-COV 2 allostasis and the people and person-centered prevention. A new prevention strategy based on people's metabolic and immune shield for the pandemic shutdown. Part 1 The Sars-Cov 2 entry and COVID-19. Milan. Università Ambrosiana , 2021. ISBN: 9798530093906  

 

 

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[16]  Brera G. R, The manifesto of Person-Centred Medicine. Medicine, Mind and Adolescence 1999.XIV, 1-2:7-11

 

 

[17]  Brera, G.R. Person-Centered Medicine and Person Centered Clinical Method. Milano: Università Ambrosiana ed.: 2021 ISBN: 9798726465432

 

 

[18] Gadamer H.G. Where health is hidden. Frankfurt; Suhrkamp Verlag, 1993 (German)

 

 

[19]  Lissoni P. The spirit marries the science. Calco, Ripamonti , 2008 (Italian)

 

 

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27  Wang W et al. Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021. JAMA Oncol. 2022 Apr 8. doi: 10.1001/jamaoncol.2022.1096. Epub ahead of print. PMID: 35394485

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 



CHIESTA L'INCRIMINAZIONE D'UFFICIO DEL COORDINATORE CTS ANTI-COVID FRANCO LOCATELLI E IL RITIRO DEI VACCINI PER BAMBINI E  ADOLESCENTI

    Dopo la richiesta d'incriminazione d'ufficio del presidente dell'AIFA Giorgio Palu', e della Presidente della Società Italiana di Pediatria , Annamaria Staiano, con un esposto diretto alle Procure della Repubblica, la Scuola Medica di Milano e il Comitato Sanitario Nazionale, alla luce dei risultati del Convegno internazionale : " Person-Centered Medicine ,Prevention,Adolescence  hanno chiesto l'incriminazione d'ufficio del coordinatore del CTS anti-COVID 19  dr.Franco Locatelli per avere divulgato pubblicamente informazioni  non vere riguardo la sicurezza dei vaccini Anti-COVID-19, per influenzare i genitori dei minori e avere  disposto la vaccinazione di bambini e adolescenti e giovani  il cui rapporto fatality/case 0-9 = 0,00003 10-19 = 0,00004 0-29= 0,00007 non giustificava la decisione.,  tenendo anche presente le possibilità di cura nei casi d'infezione, ma esponendo in questo modo bambini e adolescenti a effetti avversi, anche mortali, come è documentato, per cui il rischio vaccinale è superiore al beneficio e danneggiando la popolazione a causa del danno  all'instaurarsi dell'immunità di gregge. (leggere sotto) Il dr. Locatelli non ha inoltre messo in atto misure preventive non vaccinali efficaci per la prevenzione primaria e secondaria, semplici ed efficaci, come appare dalla letteratura, e sintetizzate nel primo trattato edito al mondo sulla prevenzione del COVID-19, scritto dal prof.Giuseppe R.Brera ,Direttore della Scuola medica di Milano e Presidente dello World Health Committee e del Comitato Sanitario Nazionale. In data 20.11.2021, la Scuola Medica di Milano ha promosso la terza sessione nel Convegno: “ Medicina centrata sulla persona, prevenzione e adolescenza” sul tema “ La Prevenzione centrata sulla persona, rischi da vaccini genetici, terapia precoce del COVID 19” i cui risultati ,tra gli altri facevano emergere l'evidenza scientifica della genotossicità dei vaccini mRNA , che con il silenziamento dei micro-RNA possono provocare leucemie, tumori solidi, danni neurologici , diminuzione attività immunitaria innata, unitamente alla  evanescenza dei loro effetti immunitari, e la mancanza di prevenzione del contagio (il Green pass non ha basi scientifiche), come appare evidente dal trend dei contagi dei vaccinati e dei loro ricoveri ospedalieri. I dati sulla genotossicità dei vaccini mRNA e dei vaccini vettoriali sono stati presentati al Congresso dal prof.Giuseppe R.Brera alla luce del lavoro, pubblicato in pre-print su Research Gate sulla materia e nei "Scientific reports della Scuola medica di Milano"e comunicati al Presidente dell'AIFA il 25 Novembre, con l'invito a non dare aitorizzazione alla distribuzione dei vaccini per i bambini  vista l'evidenza scientifica dei danni genetici ed epigenetici. Nello stesso Congresso il prof.Brera,unitamente al prof.Violato (Università di Minneapolis e Ambrosiana) avevano presentato un'analisi epidemiologica dei dati grezzi sulla mortalità da vaccini e avevano evidenziato un aumento significativo del rischio della mortalità  negli anziani vaccinati over 80, con seconda dose prima di sei mesi, rispetto ai non vaccinati e un aumento, se pur non significativo del rischio nella classe d'età 19-39 e dopo la prima dose nella classe 60-79. (Scientific reports of the Milan School of Medicine) Nel Congresso il dr. Maurizio Federico, direttore del Centro della salute globale dello ISS, che con  la sua equipe sta mettendo a punto un vaccino di grande efficacia, aveva evidenziato gli evidenti limiti dei  vaccini mRNA e vettoriali e le incongruenze sulla loro efficacia. Il 25 Novembre, il prof. Giuseppe R.Brera, direttore della Scuola medica di Milano e presidente del Comitato Sanitario Nazionale, aveva inviato le evidenze scientifiche sul rischio genotossico dei vaccini al Presidente dell'AIFA, un vero "allerta" invitando a non dare autorizzazione. La stessa cosa era stata fatta con l'EMA, ma troppo tardi e successivamente i dati  sono stati inviati al Presidente della UE von Leyden, per conoscenza. il 1 Dicembre, malgrado l'allerta, l'AIFA autorizzava la vaccinazione dei bambini  annunciando la cosa con un comunicato da cui si evince che Palu' non ha preso in minima considerazione le evidenze della genotossicità dei vaccini mRNA e il Locatelli ha immediatamente messo in atto l'organizzazione per la vaccinazione dei bambini con pronunciamenti pubblici non veritieri sulla loro sicurezza e sebbene il rapport0 fatality/cases siano prossmi allo zero e i bambini e gli adolescenti siano difesi dall'immunità innata , non  vittime ,se sani, di un infezione sistemica,  e proteggano l'intera popolazione, se il virus neutralizzato dalla loro immunità, venga lasciato circolare tra loro, come avviene con altri patogeni. Il Dr Franco Locatelli , su Avvenire  il 19 Agosto 2021,allo scopo d’ influenzare i genitori degli adolescenti e gli adolescenti per indurli alla vaccinazione ha dichiarato:  “Proviamo a fugare i dubbi che più di frequente avanzano i genitori sul punto: «I vaccini non sono sicuri», (ndr esatto)  «I rischi superano i benefici», (esatto ndr) «Mancano i dati»... continua il Dr-Locatelli: “Tutte affermazioni prive di fondamento, diffuse in modo del tutto irresponsabile. Anche le affermazioni di alcuni, pochi, politici, che hanno spesso sventolato l’esempio della “cautela” tedesca per instillare dubbi famiglie rispetto alla vaccinazione negli adolescenti sono smentite: la Germania proprio in queste ore è tornata indietro su questo punto e ha raccomandato i vaccini per tutti i soggetti nella fascia 12-18. Tutte le società scientifiche pediatriche internazionali sono largamente favorevoli alle vaccinazioni anche nei soggetti sotto i 12 anni di età: in tal senso si sono espresse la Società Italiana di Pediatria ( ndr: Il Comitato sanitario nazionale e la Scuola Medica di Milano hanno chiesto l’incriminazione d’uffcio del Presidente) e l’American Academy of Pediatrics, che anzi ha sollecitato la Food and drug administration, cioè l’agenzia regolatoria americana, a procedere celermente sulla revisione dei dati circa la sicurezza e l’efficacia dei vaccini anche per gli under 12. I vaccini sono efficaci e sicuri per queste fasce di età come si sono dimostrati esserlo per tutte le altre: non c’è alcun dato scientifico che dica il contrario e non c’è alcun motivo per pensare che non sia così.” (falso) (1) Nel merito della vaccinazione ai bambini 5-12 il Locatelli dichiara al giornale Avvenire il 1 Dicembre 2021 «Vaccinare i bambini» per non tornare indietro. Per proteggerli, tutelando la loro salute fisica e psichica, i loro contatti sociali. E perché tutti i dati, tutte le evidenze scientifiche ci dicono che è sicuro farlo. (falso) (1) (2) (3) (4)  Il coordinatore del Cts, Franco Locatelli, elenca le ragioni per cui i genitori dovrebbero decidere per le somministrazioni sui più piccoli. In dichiarazione pubbliche successive, ha esortato i genitori a far fare la vaccinazione ai bambini come “ Bel regalo di Natale”  ( una possibile leucemia o una encefalite da meningococco  potrebbe essere un bel regalo di Natale ?) [1] Lockhart J, Canfield J, Mong EF, Vanwye J, Totary-Jain H. Nucleotide Modification Alters MicroRNA-Dependent  Silencing of MicroRNA Switches. Mol Ther Nucleic Acids. 2019;14:339-350. doi:10.1016/j.omtn.2018.12.00 (2)Brera G.R Scientific evidence of mRNA and vectorial vaccines genotoxicity inducing tumors and psycho-neuro- behavioral disorders. https://www.researchgate.net/publication/356588024 I DOI: 10.13140/RG.2.2.29151.1808 (3) Federico M  Biological and immune responses to current anti‐SARS‐ CoV‐2 mRNA vaccines beyond anti‐Spike antibody production .  Proceedings  of the Conference Person-Centered Medcine,prventiona and adolescene; III° Session: Person-centered prevention,risks from genetic vaccines ,early therapy of COVID-19; 2021 Nov.20 ; Milan, University Ambrosiana. 2021.p 44-45.   Internet https://www.researchgate.net/publication/356909387_Biological_and_immune_responses_to_current_anti-SARS-_CoV-2_mRNA_vaccines_beyond_anti-Spike_antibody_production [4]   Menichella M. Una stima realistica degli effetti avversi dei vaccini anti-Covid e del rapporto rischi-benefici. Ed Fondazione Hume – 9 Novembre 2021  Internet https://www.fondazionehume.it/wp-content/uploads/2021/11/Articolo_effetti_avversi-85.pdf (5)Su R John   Myopericarditis following COVID.19 vaccination. Updating  from Vaccine Adverse Effects Reporting  System (VAERS)-August 30 Internet  https://stacks.cdc.gov/view/cdc/109492 access 15 December 2021    Alla luce di tali fatti la Scuola Medica di Milano  ha chiesto l'incriminazione d'uffcio del Dr.Franco Locatelli e il ritiro dei vaccini per i bambini con il blocco della vaccinazione dei bambini e degli adolescenti Nell'esposto, appare anche l'errore strategico, del Ministero della salute e del CTS  che con la vaccinazione di bambini e adolescenti raramenti infetti, e per lo più asintomatici e, se sani ,non a rischio di severità di COVID 19  ma comunque curabilissimi , a danno di tutta la popolazione come hanno evidenzato sul British Journal of Medicine, in modo magistrale JS Lavine, O. Bjornstad ,R Antia  : Purtroppo quando la circolazione del virus diminuisce, l’età  delle infezioni primarie aumenta e poiché l’età è direttamente associata alla patogenicità, vaccinare i bambini-aggiungo gli adolescenti- può portare con probabilità a un più basso tasso d’infezione ma a un più alto tasso di casi fatali. In addizione in dipendenza del fatto della relativa durata dell’immunità indotta dai vaccini e dall’infezione e il tasso delle mutazioni antigeniche, la vaccinazione dei bambini potrebbe aumentare la frequenza di grandi epidemie stagionali, portando a un totale aumento dell’induzione della morbidità e mortalità indotta dal virus Lavine J S, Bjornstad O, Antia R. Vaccinating children against SARS-CoV-2 BMJ 2021; 373 :n1197  doi:10.1136/bmj.n1197 Alcuni adolescenti sarebbero oggi vivi se l'Italia della sanità non fosse guidata da un analfabeta ( ben s'intende sul piano medico-scientifico), supportato da specialisti con una cultura medica frammentaria e non aggiornati sul cambiamento epistemologico della scienza medica, della clinica e della prevenzione :" La medicina centrata sulla persona" , sempre pensando a una buona fede . Pare-ma è da verificare vista la gravità- che nel 2014 l'ex ministro Lorenzin  abbia accettato di fare dell'Italia una portaerei vaccinale. Il problema alla base di tutto , anche a livello mondiale, è  il  grave ritardo nell'adotttare il cambiamento epistemologico della Medicina  ritenendola  vincolata a un paradigma meccanicista-lineare  dannoso e ormai superato. "agente patogeno- rischio di malattia-richio di morte " e non  adottando il corretto "agente patogeno-allostasi virale e antivirale-immunità innata-resilienza/vulnerabilità- salute/ rischio di malattia" E' assolutamente necessario un cambio  urgente di strategia sanitaria,  creando uno scudo metabolico -immunitario per la popolazione,  che oggi una ignorante e semi-analfabeta politica sanitaria vuole condannare a plurime vaccinazioni che hanno e avranno l'effetto paradosso di diminuire l'immunità innata , aumentando la vulnerabilità ad altri patogeni e ai tumori. Il primo passo che una Presidenza del Consiglio " illuminata" anche sollecitato da un futuro  Presidente della Repubblica , culturalmente al di sopra e "patriotta",  sarebbe quello di allontanare al piu' presto il Ministro della sanità, Roberto Speranza.   a confermare il rischio per la vaccinazione dei bambini e giovani  sono stati citati  nell'esposto: Dr.Maurizio Federico   direttore del Centro della salute globale, dello ISS Profsa  Maria Rita Gismondo- Università di Milano-Ospedale Sacco Dr. Mario Menichella -Fondazione Hume Prof.Marco Cosentino- Università dell’Insubria Stefano Dumontet Università Partenope David Conversi Università La Sapienza Maria Luisa Chiusano Università Federico II° Nicola Schiavone Università di Firenze Leonardo Vignoli Università Roma 3 Salvatore Valiante Università Federico II° Marco Milanesi Università Piemonte Orientale Carlo Gambacorti-Passerini , Univerità di Milano-Bicocca Monica Facco, Università di Padova Daniele Porretta, Università la Sapienza   a cura della  Redazione scientifica Iohannes Mazethés                
Scientific evidence of anti COVID-19 mRNA and vectorial vaccines genotoxicity inducing tumors and psycho-neuro-behavioral disorders.

scienza e caritajpg

Scientific Report of the Milan School of Medicine 2021; December 7 2021

Scientific evidence of anti COVID-19 mRNA and vectorial vaccines genotoxicity inducing tumors and psycho-neuro-behavioral disorders.

  DOI:

10.13140/RG.2.2.29151.18081

       

                                             Giuseppe R.Brera[1]

 

Summary

. Micro-RNAs (miR) are non-coding RNA filaments that control mRNA transcription. Micro-RNAs have been studied in cancer pathogenesis, metastasization, cancer therapy, the structuring of the central nervous system, diabetes, and heart disease.   Mir-134-138 regulate the development of dendritic spines needed for synapses. Their silencing can lead to autistic spectrum disorders and mental retardation and damage to brains in evolution such as childhood and adolescence, producing learning problems and mood problems, and in adults for alterations of receptors for neurotransmission. It has been shown that N1-methyl pseudouridine binds to miR and induces silencing processes, increasing cell methylome at the origin of cancer. The production of mRNA vaccines replaces Uridine with N1-methyl-pseudouridine to escape innate immunity and implement rapid translation. N1-methyl-pseudouridine binding with mi-RNA alters the epigenetic transcription of oncosuppressor that, with the increase in cell methylation, could result in the induction of tumors and relapses, natural immunity inhibition, and neuro-behavioral disorders transmissible to progeny. Vectorial vaccines hybridize the host DNA with adenoviruses and induce tumors at the experimental level. Clinical reports and long-term epidemiological investigations are necessary to verify the impact of mRNA vaccines on health.

 

 

The SARS-COV 2 pandemic developed in China most likely for a probable laboratory induction linked to the attempt to create a hybrid virus "SARS-COV-HIV" for a vaccine or other purposes; the pandemic beginning determined a race to the vaccine by "Big-pharma in opposition to the SARS-COV 1( 2002) and MERS pandemics. (2009)" disappeared without mass vaccinations. Since 2002 until 2019, BIG-Pharma omitted to invest in anti-SARS-COV vaccines aware that the speed of mutations of SARS-COV like HIV would have made research unuseful. World countries public health assessors, instead of determining a secondary prevention strategy to protect o people with comorbidities at risk of lethality (92%) based on a careful study of the literature on SARS-COV 1 for preventive purposes, wholly omitted the person-centered indeterministic approach to medicine inspired to Person-Centered Medicine, the medical science paradigm revolution[2] [3] [4] [5] [6] [7] The omissions of the WHO and national governments, based on an illiterate epistemological error leading to an approach to pandemics with a mechanistic, linear model: "virus-infection- disease-death risk and not virus-allostasis-natural immunity-vulnerability risk-disease risk- death risk" oriented only to a mechanistic adaptive immunity induced by experimental genetic vaccines not tested for long-term adverse effects with insufficient and criticized trials.[8] [9] This illiteracy-based error in promoting global health has resulted in a preventive strategy failure affecting human rights and the economy, leading to 5 million deaths and in Italy to about 150,000 (at the date). In Italy, legislation induced vaccination with blackmail, such as the loss of work which showed only for older than 39 a preventive efficacy in intensive care admissions rate and lethality.[10]

Epidemiological elaboration of data from  the Italian "EPICENTRO Istituto Superiore di Sanita'" ( October 9-November 10) shows in oldest people > 80 after two doses of vaccines < 6 months  an increase of lethality risk compared with unvaccinated (OR 1.59-IC q.1.2356 to 2.0587 P=0.0003 and a non-significant increase of lethality  in the vaccinated range 12-39: OR 1.2-CI 0.1691-8-8229    

                 

                                                                                 

 

In oldest people > 80, there is a higher mortality rate (OR = 1.5949, p < .001) for the full vaccinated (two doses) within 6 months compared to unvaccinated and a tendency in 12-39.

 

 

There is a tendency to increase risk of lethality in the vaccinated compared to unvaccinated in the range 60-79 close to 0,5 significance: OR 1.23 ( CI 0.5686 to 2.6962-P =0,5904) present in 60-79 people.

 In > 80, the lethality risk of vaccinated people is less than the full cycle of vaccination. (OR = 1.07 ,CI 0.5397 to 2.1330P = 0.5904. In other ages, first doses and full cycle of vaccination appear to be a protective factor from lethality, < 6 months from the first dose.

To date, the vaccines' failure to determine a durable immunity longer than 3-4 months for vectorial vaccines and six months for mRNA vaccines induced public health assessors to induce a third dose boosting without any consideration of adverse effects and possible alternative preventive measures.[11]

                                               

The Italian population has been inundated with statements by the central health government and regional governments driven media inducing vaccination or by mediatic virologists also based on false public statements. It occurred with a vaccination campaign for children, adolescents, and young people, not at risk of COVID-19, that if rarely infected, they are asymptomatic and with a ratio of cases/fatality to zero or almost. Roberto Speranza, the Italian Health Minister, declared "The full agreement of all scientists" about the need for vaccination in all ages." Franco Locatelli, the director of the Anti SARS-COV Italian Technical, stated on August 20 the inexistence of adverse effects for adolescents to induce parents' authorization after the news of healthy adolescents' deaths after vaccination from Italy and USA and signalization of adverse effects by USA CDC, also in contrast with health policy of countries like the UK.

Lethality from COVID-19 concerns 92,8% of people with comorbidities [12] characterized by atherosclerosis which leads to an auto-immune phenotype and immune anergy after the 7th day of the disease, the actual cause of lethality [13] confirming the theories of the relativity of the infection to cholesterol concentration in lipid rafts and the caveolar lipid rafts number and the probability of severe clinical syndrome relative to the LDL/HDL ratio and phospholipase concentration in the cell membrane, one factor altering the immune signal transduction. [14]

Recently, Maurizio Federico, with a significant review[15] in a very profound and straightforward way, highlighted that the mRNA vaccines have hard limits in immunogenicity. Vaccines have limited usefulness in time and are restricted to RBD of viral S-proteins of the original viral strain, losing effectiveness with variants because of the "Original antigenic sin. Vaccines do not stop contagions because they do not produce neutralizing antibodies (IGA)  in mucous membranes of the pharynx and upper respiratory ways, so laws that lead to the obligation to vaccination certificates appear without any scientific reason.  They do not induce resident memory B-cells in lungs, not preventing the first cause of lethality, but only IGG in the bloodstream.  Moreover, they select variants whose viral allostasis completely escape any previously vaccine-induced immunity. Moreover, restrictions hamper the asymptomatics-and healed-induced herd immunity, while there is the possibility to treat the infection early with efficacy,[16] identifying people at risk with the probability theory of the COVID-19 severity. [17]

In the light of the only IGG stimulation and the lack of activation of resident memory B-cells in the lung, the antiviral effectiveness of mRNA vaccines is a conundrum.

          Viruses lead to asymptomatic infections, depending on innate and adaptive immunity, as happens for most people every week with different species of virus and that for SARS_COV 2 is due to the immunization from other non-dangerous coronaviruses, such as corona-adenoviruses which target at least 50% of people who reach a partial immunity also to SARS-COV 2, because of common antigens. On the other hand, infections depend on the protective factors that stimulate natural immunity, eliminating the virus before it reaches the epithelial and endothelial cells. Infection is only possible on the condition of degeneration of the cell membranes due to cholesterol and LDL, inducing the formation of lipid rafts whose caveolae are the obligatory gates to the infection.[18] The oldest people with atherosclerosis–based comorbidities are more at risk of lethality because of immune anergy. Conversely, infections are rare and almost asymptomatic, with a low infectivity index in children and young people with healthy cell membranes. It has been computed that corona-adenoviruses immunize at least 50% of people. Antibodies against these neutralize vectorial vaccines adenoviruses vectors.   Vaccinations with viral vectors are dangerous for children and adolescents closer to infections for the intensity of immunity reactions leading to the risk of disease from immunocomplexes and an increased thrombophilia.[19] [20]  In Italy and adolescents died of thrombosis after the boosting dose of AstraZeneca.

The vaccines authorized by the Italian AIFA are genetic because they use genetic mechanisms to induce an artificial immunity against a particular "Spike-protein" defined by a messenger RNA code of the Huwan strain that allows the activation of adaptive cell immunity through activated lymphocytes T and B that with their proliferation assure a minimal immunity over time, not inhibiting the contagion. [21]

The mRNA vaccines are constructed with a sequence of bases homologous to RBD of the viral spike protein. The code is then transcribed by the RNA transfert, which allows the viral protein synthesis in the cytoplasm and in the organelles (endoplasmic reticulum and Golgi apparatus) to form the new virus. The mRNA vaccine is conveyed by lipid nano-particles that favor its entry into the cell membrane. The infected caveolae of the lipid rafts alter the transduction of immunity signals inhibiting proliferation and activation of lymphocytes T and B, but this is undoubtedly related to the alteration of the cell membrane and the flooding of macrophages with cholesterol and PH. Immunosenescence and the previous immune-atherosclerosis phenotype inhibit adaptive immunity and memory-t and b cells production. [22] The virus dissemination is relative to a previous immunosuppressive phenotype and "inflammaging" induced by atherosclerosis inducing a lethality risk for the oldest people with comorbidities associated with atherosclerosis, like diabetes, obesity, hypertension, cardiovascular diseases. It explains the higher rate of mortality of the immunosenescent oldest people. The SARS-COV 2 Immunity hijacking appears mediated by MTTL3, which blocks the RIG-1 receptors recognition.[23]

The mRNA vaccines induce a high IFN gamma reaction and stimulate CD4 TH1 cells in local lymph nodes, but neither induce the antiviral CD8+ mediated immunity[24] because they do not stimulate synthesis nor interact with the lung B-cell memory-resident cells, not activating these. The immunity induction of mRNA vaccines is a "conundrum." [25]

The heterologous "mRNA" inoculated with the vaccine "infects" all the immune, epithelial, endothelial cells, neurons in every anatomical structure, from the brain to the heart, the endocrine organs, and the toe.

The problem that viro-immunologists[26] had to face was to prevent the inoculated heterologous m-RNA from being recognized by Toll-like receptors (TLR). [27] For this purpose, in m-RNA, they replaced a base: Uridine with n1-methyl pseudouridine, which escapes immune control of the inoculated host and increases translation speed. In 2019 J. Lockhart, J Canfield J, Mong EF et al.[28]  demonstrated that the replacement of the Uridine of the Spike Protein mRNA with the n1methyl-pseudouridine that is necessary for the mRNA production alters the silencing of micro-RNA switches leading to a decrease in the activity of these molecular switches, called "the dark matter" of the cell (about 50% of RNA) and thus altering the processes of silencing.  What happens if the repressor of an oncogenesis inhibitor is not silenced?

        N1-methyl-pseudouridine binds to miR, altering their action to silencing miRNAs, possibly harming the organism's life. Micro-RNAs are filaments of non-coding RNA that, thanks to the "Argonaut" proteins after joining the "RISC (RNA-induced silencing complex, RNA-induced silencing complex), interact internally with the target RNA, preventing transcription by preventing the synthesis of the protein with the specific mRNA silencing. After their discovery in 1993 by Victor Ambros, Rosalind Lee, and Rhonda Feinbaum, the role of particular microRNAs was studied in pathogenesis and cancer therapy, in the structuring of the central nervous system, in diabetes, in heart disease. For example, if mi-RNA 205 is inhibited in the pathogenesis of breast cancer, carcinogenicity and metastasisation are encouraged. The same occurs for mi-RNA 21 for liver cancer. In 2009 G. Schratt, with a great contribution, illustrated some fundamental actions of miR in neurons. Mir-134-138 regulate the development of dendritic spines needed for synapses.[29] Their alteration can lead to autistic spectrum disorders and mental retardation and in brains in development as in childhood and adolescence, to learning and mood problems, as well as in adults to neuro-transmission receptor alterations such as CAMKII and CREB. Regulation of innate immunity involves mi-RNA 155-146 -132 as illustrated by J. Raisch, A.Darfeuille-Michaud, HT. Nguyen in their elegant review of 2013.   Mir-155 regulates the suppression of the cytokine signaller (SOCS)-1, which negatively regulates the capacity of the "Antigen Presenting Cells " APC to present antigen and activate lymphocytes.[30] [31]   Cells with the lack of mir-155-show a defective presentation of antigen and therefore cannot activate T cells to promote the TH1-induced inflammation [32]: this could be the epigenetic pathogenesis of anergia and immunosenescence. Another study has shown that the elimination of mir-155 expression significantly increases the expression of the pro-inflammatory IL1. These observations depict how mRNA vaccines could induce paradoxical inhibition of innate immunity, increasing people's vulnerability to infection and cancer. In atherosclerotic M2 immune phenotype, present in comorbidities at risk of COVID-19 severity,[33] it could induce anergy when there are other infections with SARS-COV 2 variants escaping previous and waning adaptive immunity in short-time, exposing oldest immunosenescent people to a clinical syndrome severity up to lethality. Moreover, the induced methylation by mRNA vaccines, resulting in an MTTL3 cellular increase, supports the viral hijacking of immunity by SARS-COV 2 variants, and reducing natural immunity. It means that more mRNA vaccines are inoculated, more natural immunity is reduced, making easier variants’ immunity hijacking.

Numerous studies document how dysregulation of mi- RNA is associated with cancer development and metastasis processes, as documented by the splendid review of G. Sotiropoulou, G. Pamplakis, E.Lianidou Pampalakis, Lianidou, Z. Mourelatos. Cancer pathogenesis is associated with several bio-molecular processes such as genomic alterations, transcription of oncogenic factors, and inhibition of repressors transcription, such as P53 and hypoxia.

Epigenetic changes are regulated by micro-RNAs which are the arbiters of cell health as on/of molecular switches of mRNAs.

Viral mRNAs such as mRNA vaccines act by altering microRNAs. The mRNA vaccines act like a virus at the epigenetic level.

Recently E Karimi, H. Azari Yari, M, Tahmasebi, et al. identified 39 mi-RNA derived by Sars-COV 2 inducing a viral allostasis inhibiting the innate immunity, altering Vit. D and the lung cells metabolism through the transcription alteration.[34]   

The silencing of miR-223 appears to be caused by an epitranscryptomic alteration of pre-micro-RNA, which produces an oncogenic factor that binds to its site, producing its "switching off." This is associated with leukemia pathogenesis. An epidemiological study on the incidence of post-vaccine leukemia and other cancers is needed. The direct induction of miR dysregulation produced by mRNA vaccines can have dramatic consequences for millions of young people and children by inducing the pathogenesis of tumors or relapses and diseases of the central nervous system. What will be the effect of mRNA vaccines on the brain of the ruling class since their action determines alterations of the miRNA that control neuronal nuclei biological substrate of the cognitive and subcortical sphere. What will happen with the impairment of the activity of the cerebral cortex and the subcortical nuclei?

 There is a pandemic of illiterate criminality in people who want to induce the vaccination of adolescents and children who are not at risk of COVID-19. If rarely infected, children are asymptomatic[35] thanks to their solid innate immunity and rapidly reduce the viral load in the oral and nasal mucous membranes. Children and adolescents and asymptomatic people could act as "living vaccines" contributing to the" herd immunity" as often occurs with other viruses. It has been well highlighted that asymptomatic people relatively contribute to the virus diffusion. Vaccination exposes children and adolescents to epigenetic and genetic damages whose impact must be studied with epidemiological investigations but is sure.

Two meta-analyses show the reduced infectivity of asymptomatic people (AIC). Transmission rates of AIC ranged from 0–2.2% compared to 0.8–15.4% for symptomatic (SIC)[36]and in the household from 0–4.9% compared to 18.0% of SIC. [37] .

The infectivity reduction of asymptomatic people is probably due to the presence of neutralizing IGA in mucous membranes, absent in vaccinated people.

A study that monitored 455 contacts exposed to the asymptomatic COVID-19 virus carrier showed that nobody was infected.[38]

The reduced viral load transmission by the upper respiratory and its disappearance in a shorter time can explain this evidence and reverses the common belief that asymptomatic people induce the pandemic. Conversely, a reduced transmissible viral load to healthy people could activate the people's innate immunity and the progressive loss of virulence by activating the tissue-resident memory T cells that block the virus diffusion in the organism.

The right strategy to accelerate herd immunity is a health education campaign to educate to assume immunogenic molecules (e.g., beta-glucans in bakers yeast) and inhale vapors of powerful common natural antiviral substances at the first signals of infection of upper respiratory ways.[39]

The SARS-COV 1( 2002-2003) and MERS (2009-2010) disappeared without vaccines.

What will happen in millions of adolescents and young people not at risk of COVID-19 that the Italian health management and other countries led to vaccination with a legalized blackmail, because of the alteration of the regulation of mir-223, whose alteration is linked to the pathogenesis of leukemia? In the USA, the FDA recently approved mRNA vaccines in children based on a small Pfizer trial, which used children as experimental animals and that did not monitor the adverse effects at the epigenetic level and their manifestation after a long time.

The other process induced by mRNA vaccines is the cell's methylation induced by n1-methylpseudouridine. The n1-methylpseudouridine (ɸ) stabilizes the RNA. It is naturally present more in the RNAt, with implicit natural finalism to favor the coding probably. In synthesizing the mRNA vaccines, the Uridine has been replaced with ɸ to increase the translation speed and evade the natural immunity. However, introducing ɸ in each cell produces cellular stress that could be equivalent to "heat stress" that produces an 'increase of cell methylome by methylating all the bases through the synthesis induction of METTL3 (methyltransferase like 3) with the finalism to ensure an allostasis for survival. The METTL3 binds to microRNA, causing the down-regulation of some and up-regulation of others. The action of miR like that of antisense RNA could produce the silencing of the P15 gene, which encodes a dependent cycline kinase involved as a repressor of malignant leukemic degeneration. W Yu, D Gius, P. Onyango, et al. in 2008 saw an inverse relationship between P15 and leukemia, highlighting the risk of its repression. Antisense RNA also interacts directly or indirectly with DNA-methyltransferase leading to DNA methylation and its consequences in the repression of gene transcription and the recruitment of "histone-modifying enzymes" by modifying chromatin.

This evidence means that in opposition to an illiterate bio-medical culture, mRNA vaccines also induce genetic alteration that, in addition to induction or suppression of miR, lead to DNA methylation and modification of chromatin.

Moreover, the increase in cell methylome could be caused by the lack of repression of the MTTL3 synthesis by silencing its mRNA induced by a specific micro-RNA. The MTTL 3 increase induces the general methylation of nucleotidic bases with catastrophic effects, a sort of earthquake in the organism's life, with dramatic effects on the pathogenesis of tumors.

In the tissues of patients with "Non-small cell lung cancer (NSCLC) (small cell lung cancer) "N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3)" regulates microRNA-1246 (mir-1246) which is a well-documented tumor's progression and metastases. More METTL3 and mir-1246 were found in these tissues in inverse ratio to PEG-3 ( Paternally expressed gene-3).[40]

The alteration of micro-RNA is, therefore, very dangerous. This confirms the aversion of Luc Montagnier, Nobel Prize, against the use of genetic vaccines before knowing in depth their effects with long-term epidemiological investigations.

Several deaths and adverse effects on mRNA vaccines have already been reported worldwide, [41] such as the high incidence of pericarditis and myocarditis in young people, which in some countries like the UK, has blocked any other vaccination in adolescents and young people, not at risk of COVID-19. In Italy, a teenager died a few hours after the second vaccination by m-RNA, another from the vectorial Astra-Zeneca. In the USA, the CDC reported the deaths of 14 teenagers. The actual extent of these events is entirely unknown because public health, organizations such as AIFA, the Ministry of Health, the Italian Higher Institute of Health, to our knowledge, have not organized epidemiologic research to study the adverse effects of these vaccines over time.

Undoubtedly the fear of COVID-19,   induced by a virus quickly and destroyable and neutralizable with natural antiviral remedies also immunogenic and drugs already in use, [42] that prevents contact with epithelial and endothelial cells is derived from the lack of public health orientation towards “Person Centered Prevention”[43] , and to failure in primary and secondary prevention. This omission is due to ignorance and the non-adoption in public health of the multi-factorial, multi-dimensional paradigm of "Person-centered medicine," the paradigm change of medical science, that could have saved only in Italy 150.000 and in the world millions of people. As Luc Montagnier claims, we need analysis over a long time to control the existence of adverse effects, even fatal at a short time. The only answer to the pandemic beginning and permanence has been the adoption of "genetic" vaccines, which have been inadequately tested and limited in time, with the scientific evidence of their danger. The adverse effects of these vaccines and the induction of variants endanger the health of millions of people and must be prevented or blocked in time to avoid a global health disaster, primarily protecting children and adolescents whose health is to date menaced by mRNA vaccines.

The mRNA vaccines' dangers, as highlighted above, are shared by the viral vector vaccines. These induce a modification of human DNA because of the recombination of the animal or human  DNA vector adenovirus with the host's DNA. This hybridization could lead to auto-immune reactions and, at the experimental level, to an impressive induction of tumors. [44]

Scientific evidence of the anti SARS_COV 2 vaccines- induced genetic damages must be studied with clinical and epidemiological investigations. However, before it is necessary a total change of public health administration resulting in the withdrawal of the authorizations to mRNA vaccines distribution and the constitution of a metabolic and immune shield for the population by adopting the "Antiviral allostasis, and immuno-stimulation"[45] strategy launched in Italy by the National Health Committee and in the world by the World Health Committee.

 Unfortunately, the prudence towards vaccines that led to their rejection only by a minority of the population and health care workers has a sound scientific basis. The dramatic suspension of health care workers who refused vaccination by a surprising (in the negative sense) physician's council and discrimination of workers paradoxically supported by unions - but unions should not defend workers? -that do not want to vaccinate is without any scientific basis.

  What can also happen to the brain, mind, and behavior of the national leadership, institutional public or business, teachers, and in any context with the genes of the adenovirus of chimpanzees integrated into the genome of cortical neurons or sub-cortical brain (Astra-Zeneca vaccine) that, if in age, communicate to the progeny?  Will the COVID-19 contribute to human evolution?

Clinical reports and long-term epidemiological investigations are necessary to verify the impact of mRNA vaccines on health.

 



  [1] Milan School of Medicine/ Scuola Medica di Milano , World Health Committee,


[2]    Brera G.R. The manifesto of Person-Centered Medicine. Medicine, Mind Adolescence,1999; Vol. XIV, n. 1-2:3-7

    Internet: www.unambro.it

 


[3]    WHO Person-centered Medicine and Medical Education. (internet) Geneva: WHO Symposium; 4 May 2011. WHO A Internet   http://www.unambro.it/html/pdf/All_Symposium_Education_People_Centred_4May2011.pdf

 


[4]    Brera G.R. Person-centered Medicine: Theory, Teaching, Research. Int.J.Pers. Cent.Med 2011; 1 (1):69-79

 


[5]    Università Ambrosiana. Medical Science and Health Paradigm Change . G.R Brera ed: Proceedings from the   Conference: Medical Science and Health Paradigm Change. Milan 13-14-15 October 2017. Internet: www.healthparadigmchange.it

 


[6]    Brera G.R. The Person-centered Health Paradigm and its impact on health sciences.(Internet) Research Gate 2015   DOI:10.13140/RG 2.1.2594.1925 2015-05-21 T 15:42:05 UTC. Available from

    https://www.researchgate.net/publication/277010325

 


[7]   Brera, G.R Person-Centered Medicine, and Person-Centered Clinical Method. Milano: Università Ambrosiana ed.: 2021 ISBN: 9798726465432

 


[8]    Doshi P. Will covid-19 vaccines save lives? Current trials aren’t designed   to   tell us. BMJ 2020;371:m4037 http://dx.doi.org/10.1136/bmj.m4037

      Published: 21 October 2020

 


[9]    Topol EJ. Paul Offit’s biggest concern about covid vaccines. 2020.   https://www.medscape. com/viewarticle/936937


 

[10]     Italian health Institute-Epicentro Pandemic  COVID-19  Updating August 18 2021

       Internet https://www.epicentro.iss.it/coronavirus/bollettino/Bollettino-sorveglianza-integrata-COVID-19_18-       agosto-     2021.pdf


[11]    Eliakim-Raz N, Leibovici-Weisman Y, Stemmer A, et al. Antibody Titers Before and After a Third Dose of the SARS-CoV-2 BNT162b2 Vaccine in Adults Aged ≥60 Years. JAMA. Published online November 05, 2021. doi:10.1001/jama.2021.19885


[12]  Antos A, Kwong ML, Balmorez T, Villanueva A, Murakami S. Unusually High Risks of COVID-19 Mortality with Age-Related Comorbidities: An Adjusted Meta-Analysis Method to Improve the Risk Assessment of Mortality Using the Comorbid Mortality Data. Infect Dis Rep. 2021;13(3):700-711. Published 2021 Aug 8. doi:10.3390/idr13030065

 


[13]  Brera G.R . SARS-COV 2- allostasis and the people and person-centered prevention. Part 2 The sars-cov 2- induced    immunosuppression and covid-19 anergy . Part 3 The antiviral metabolic allostasis and preventive immunostimulation - How to induce zero risk for covid-19. Milan: Ambrosiana University: 2021 ISBN 9798547583520

 


[14]  Brera G.R Sars-Cov-2 allostasis and the people and person-centered prevention. A new prevention strategy based  on a people metabolic and immune shield for the pandemic shutdown. Part 1 The Sars-Cov 2 entry and COVID-19. Milan. Università Ambrosiana , 2021. ISBN: 9798530093906

 


[15]  Federico M Biological and immune responses to current anti‐SARS‐ CoV‐2 mRNA vaccines beyond anti‐Spike antibody production . Proceedings of the Conference Person-Centered Medcine,prventiona and adolescene; III° Session: Person-centered prevention,risks from genetic vaccines ,early therapy of COVID-19; 2021 Nov.20 ; Milan, University Ambrosiana. 2021.p 44-45.  

 


[16]  Suter F, Consolaro E, Pedroni S, Moroni C, Pastò E, Paganini MV, Pravettoni G, Cantarelli U, Rubis N, Perico N, Perna A, Peracchi T, Ruggenenti P, Remuzzi G. A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: A retrospective observational matched-cohort study. EClinicalMedicine. 2021 Jul;37:100941. doi: 10.1016/j.eclinm.2021.100941. Epub 2021 Jun 9. PMID: 34127959; PMCID: PMC8189543.


 

[17]   Brera G.R Sars-Cov-2 allostasis and the people and person-centered prevention. A new prevention strategy based on a people metabolic and immune shield for the pandemic shutdown. Part 1 The Sars-Cov 2 entry and COVID-19. Milan. Università Ambrosiana , 2021. ISBN: 9798530093906


 

[18]   Ibidem 15

 


[19]    Federico M The conundrum of current anti-SARS-CoV-2 vaccines. Cytokine & Growth Factor Reviews.2021;60:45-61.

 


[20]    Doerfler W. Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human Genome - Are Adenoviral Genes Expressed in Vector-based Vaccines? Virus Res. 2021 Sep;302:198466. doi: 10.1016/j.virusres.2021.198466. Epub 2021 Jun 1. PMID: 34087261; PMCID: PMC8168329.

 


[21]    Ibidem 13

 


[22]    Ibidem 3

 


[23]    Li N, Hui H, Bray B, et al. METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection. Cell Rep. 2021;35(6):109091. doi:10.1016/j.celrep.2021.109091

 


[24]    Cagigi, A.; Loré, K. Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans. Vaccines 2021, 9, 61. https://doi.org/10.3390/vaccines9010061

 


[25]    Federico M The conundrum of current anti-SARS-CoV-2 vaccines. Cytokine & Growth Factor Reviews.2021;60:45-61.


[26]    Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-854.

 


[27]    Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, et al. Foxp3-dependent microRNA155 confers competitive fitness to Regulatory T cells by targeting SOCS1 protein. Immunity. 2009;30:80-91.


 

[28]    Lockhart J, Canfield J, Mong EF, Vanwye J, Totary-Jain H. Nucleotide Modification Alters MicroRNA-Dependent      Silencing of MicroRNA Switches. Mol Ther Nucleic Acids. 2019;14:339-350. doi:10.1016/j.omtn.2018.12.00

 


[29]  Schratt G. microRNAs at the synapse. Nat Rev Neurosci. 2009 Dec;10(12):842-9. doi: 10.1038/nrn2763. Epub 2009 Nov 4. PMID: 19888283.

 


[30]  Raisch J, Darfeuille-Michaud A, Nguyen HT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19(20):2985-2996. doi:10.3748/wjg.v19.i20.2985


 


[32]  Strains M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA, Pierre P. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA. 2009;106:2735-2740

 


[33]  Brera G.R . SARS-COV 2- allostasis and the people and person-centered prevention. Part 2 The sars-cov 2- induced    immunosuppression and covid-19 anergy . Part 3 The antiviral metabolic allostasis and preventive immunostimulation - How to induce zero risk for covid-19. Milan: Ambrosian University: 2021 ISBN 9798547583520


[34]  Karimi E, Azari H, Yari M, Tahmasebi A, Hassani Azad M, Mousavi P. Interplay between SARS-CoV-2-derived miRNAs, immune system, vitamin D pathway and respiratory system. J Cell Mol Med. 2021;25(16):7825-7839. doi:10.1111/jcmm.16694


 

[35]    Erika Molteni, H. Sudre, Liane S. Canas, Sunil S. Bhopal, et al. Illness duration and symptom profile in a large cohort of symptomatic UK school-aged children tested for SARS-CoV-2. Lancet; 2021 internet   file:///C:/Users/Utente/Documents/UA/ricerca/Corona%202/Illness%20duration%20and%20symptom%20profile%20in%20symptomatic%20UK%20school-aged%20children%20tested%20for%20SARS-CoV-2%20-%20The%20Lancet%20Child%20&%20Adolescent%20Health.html

 


[36]  Byambasuren O.Cardona M.Bell K.et al. Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis.J Assoc Med Microbiol Infect Disease Canada (JAMMI). 2020; 4: 223-234

 


[37]  Madewell ZJ, Yang Y, Longini IM, et al. Household Transmission of SARS-CoV-2. A systematic review and meta-analysis. JAMA Netw Open 2020;3(12):e2031756.doi: 10.1001/jamanetworkopen.2020.31756. 12.18.2  

 


[38]  Gao M, Yang L, Chen X, et al. A study on infectivity of asymptomatic SARS-CoV-2 carriers. Respir Med.      2020;169:106026. doi:10.1016/j.rmed.2020.106026

 


[39]  Brera G.R . SARS-COV 2- allostasis and the people and person-centered prevention. Part 2 The sars-cov 2- induced    vimmunosuppression and covid-19 anergy . Part 3 The antiviral metabolic allostasis and preventive immunostimulation - How to induce zero risk for covid-19. Milan: Ambrosian University: 2021  ISBN 9798547583520

 


[40]   ShaohongHuang,ShaoningLuo,ChulianGong,LiminLiang,YiXiao MinganL,JinyuanHe MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting pateRNAlly expressed gene 3

            Datamolecular Therapy - Nucleic Acids, ISSN: 2162-2531, Vol: 24, Page: 542-553 Publication Year2021

 


[41]    Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA. 2021;326(14):1390–1399. doi:10.1001/jama.2021.15072


 

[42]   Ibidem 13


 

[43]


[44]  Doerfler W. Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human Genome - Are Adenoviral Genes Expressed in Vector-based Vaccines? Virus Res. 2021 Sep;302:198466. doi: 10.1016/j.virusres.2021.198466. Epub 2021 Jun 1. PMID: 34087261; PMCID: PMC8168329

 


[45]  Brera G.R . SARS-COV 2- allostasis and the people and person-centered prevention. Part 2 The sars-cov 2- induced     vimmunosuppression and covid-19 anergy . Part 3 The antiviral metabolic allostasis and preventive immunostimulation - How to induce zero risk for covid-19. Milan: Ambrosian University: 2021 ISBN 9798547583520

 



SIGNIFICANT INCREASE OF MORTALITY IN >80 ANTISARS-COV VACCINATED PEOPLE COMPARED TO UNVACCINATED AND 12-39 PEOPLE

SIGNIFICANT INCREASE OF MORTALITY IN >80 ANTI-SARS-COV VACCINATED PEOPLE COMPARED TO UNVACCINATED AND 12-39 PEOPLE AND THE ANTI-COVID 19 VACCINES GENOTOXICITY


Brera G.R- *, Violato C**

Raw data from the Italian “ EPICENTRO Istituto Superiore di Sanita’” ( October 9-November 10), depict a lethality of unvaccinated people N = 162 and n= 214 in vaccinated people with anti-SARS-COV vaccines. The type of vaccine is unspecified but presumably is mRNA.

Epidemiological elaboration of data shows in oldest people > 80 after two doses of vaccines < 6 months a significant increase of lethality risk compared with unvaccinated (OR 1.59-IC q.1.2356 to 2.0587 P=0.0003 (table 1)  and a non-significant increase of lethality in the vaccinated range 12-39: OR 1.2-CI 0.1691-8-8229 (TABLE 2)  (raw data are small).

                                                    Table 1

VACCINATION RISK FOR OLDER PEOPLEpng

                                                              Table 2    


           Odds ratio

1.2074

           95 % CI:   

0.1691 to 8.6229

           z statistic       

0.188

           Significance level

P = 0.8510



                    After the first dose, there is  a tendency to an increased risk of lethality in the vaccinated compared with unvaccinated in the range 60-79 close to 0,5 significance: OR 1.23 ( CI 0.5686 to 2.6962-P =0,5904)  (Table 3)

(Table 3). In > 80 the lethality risk of vaccinated people is less than the full cycle of vaccination. (OR = 1.07 ,CI 0.5397 to 2.1330P = 0.5904. (Table 4)

 

          Table 3                 

            Odds ratio

1.2382

            95 % CI:      

0.5686 to 2.6962

            z statistic

0.538

          Significance level

P = 0.5904


         Risk of the lethality of 60-79 vaccinated people after 1 dose of vaccine compared to unvaccinated                           

    
TABLE 4

            Odds ratio

     1.0729

            95 % CI:

 0.5397 to 2.1330

            z statistic      

0.201

          Significance level

P = 0.8409

Risk of the lethality of >80 0F vaccinated people after 1 dose of vaccine compared to unvaccinated


The increased risk of mortality in>80 could be explained by a direct effect of mRNA vaccines inducing genotoxicity from the micro-RNA silencing of the innate immunity, caused by the vaccines' n1-Methil pseudouridine binding with micro RNA and immunosenescence.
Genotoxicity of mRNA and vectorial vaccines is well documented and exposes people to severe adverse effects like tumors, self immunity,psycho-neurobehavioral disorders, inhibition of natural immunity. ( 1 ,2, 3, 4, 5, 6, 7,8 )
There is also an actual incoherence between scientific data and the apparent successful general induction of lethality reduction by vaccines.
mRNA vaccines do not induce CD8+ synthesis but only activate APC to produce an IFN gamma-induced CD4-TH1 increase in local lymph nods close to the inoculation site, not joining lungs and activating residents memory cells responsible for preventing respiratory infections. Moreover, they do not induce immunity in the mucous membranes of the pharynx and upper respiratory ways because IGAs are absent. This evidence presents the political decision for the Green Pass to protect from contagion without any scientific basis. Anti-SARS COV to date available loss their efficacy in a short time because of the "Original antigenic sin". (9, 10)
The Italian population has been inundated with a pro-vax campaign by the Italian central health and regional governments supported by media-inducing vaccination and mediatic virologists. There is a pandemic of ideological and false statements, as it occurred with a vaccination campaign for adolescents and young people not at risk of COVID-19, that if rarely infected, they are asymptomatic and with a ratio of cases/fatality to zero or almost. Roberto Speranza, the Italian Health Minister, declared "The full agreement of all scientists" about the need for vaccination in all ages". Franco Locatelli, the director of the Anti SARS-COV Italian Technical, stated on August 20 the inexistence of adverse effects for adolescents to induce parents' authorization after the news of healthy adolescents' deaths after vaccination from Italy and USA and signalization of adverse effects by the USA CDC, also in contrast with health policy of countries like the UK and the WHO opposite suggestions.
There is an emergency to block the delusional idea to submit to vaccination 5-12 children and to block adolescents' and > 80 older people's vaccination. Children and adolescents are not at risk of COVID-19 . are rarely infected and almost asymptomatics, and in such a way, they contribute to realizing the "herd immunity." (11). Asymptomatic people do not transmit infection as symptomatic do. (12,13,14)
There is an urgent need for a full shift of public health policy that must be primarily addressed to older people with comorbidities at risk of lethality. 92 % of lethality  associated with COVID-19 is determined by comorbidities. Primary and secondary prevention must be established by adopting the Person-Centered Prevention paradigm inspired by the Person-Centered Medicine change of the medical science paradigm. (15, 16, 17, 18 ,19 ,20 , 21 ,22 ) This change, unknown by most public health administrators for scientific and epistemological ignorance, leads to induce a metabolic and immunostimulant shield through the institution of the "Antiviral allostasis and preventive immunostimulation" able to neutralize the Sars-Cov 2 binding to receptors, entry, replication, and to induce cross-prevention against non-communicable diseases like cancer. (23, 24)


References

1. Italian health Institute-Epicentro Pandemic COVID-19 Updating August 18 2021Internet https://www.epicentro.iss.it/coronavirus/bollettino/Bollettino-sorveglianza-integrata-COVID-19_18-ag...     2021.pdf

2 Lockhart J, Canfield J, Mong EF, Vanwye J, Rotary-Jain H. Nucleotide Modification Alters MicroRNA-Dependent Silencing of MicroRNA Switches. Mol Ther Nucleic Acids. 2019;14:339-350. doi:10.1016/j.omtn.2018.12.00

3  Doerfler W. Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human Genome - Are Adenoviral Genes Expressed in Vector-based Vaccines? Virus Res. 2021 Sep;302:198466. DOI: 10.1016/j.virusres.2021.198466. Epub 2021 Jun 1. PMID: 34087261; PMCID: PMC8168329

 4 Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009;30:80-91.

5 Schratt G. microRNAs at the synapse. Nat Rev Neurosci. 2009 Dec;10(12):842-9. DOI: 10.1038/nrn2763. Epub 2009 Nov 4. PMID: 19888283.

6 Raisch J, Darfeuille-Michaud A, Nguyen HT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19(20):2985-2996. doi:10.3748/wjg.v19.i20.2985

7 Strains M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA, Pierre P. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA. 2009;106:2735-2740

8 ShaohongHuang, ShaoningLuo, ChulianGong, LiminLiang, YiXiao MinganL, JinyuanHe MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting pateRNAlly expressed gene 3Datamolecular Therapy - Nucleic Acids, ISSN: 2162-2531, Vol: 24, : 542-553. 2021

9 Federico M Biological and immune responses to current anti‐SARS‐ CoV‐2 mRNA vaccines beyond anti‐Spike antibody production   paper submitted to Medrix

10 Federico M The conundrum of current anti-SARS-CoV-2 vaccines. Cytokine & Growth Factor Reviews.2021;60:45-61.

11  Erika Molteni, H. Sudre, Liane S. Canas, Sunil S. Bhopal, et al. Illness duration and symptom profile in a large cohort of symptomatic UK school-aged children tested for SARS-CoV-2. Lancet; 2021 internet   file:///C:/Users/Utente/Documents/UA/ricerca/Corona%202/Illness%20duration%20and%20symptom%20profile%20in%20symptomatic%20UK%20school-aged%20children%20tested%20for%20SARS-CoV-2%20-%20The%20Lancet%20Child%20&%20Adolescent%20Health.html

12 Byambasuren O.Cardona M.Bell K.et al. Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis. J Assoc Med Microbiol Infect Disease Canada (JAMMI). 2020; 4: 223-234

13 Madewell ZJ, Yang Y, Longini IM, et al. Household Transmission of SARS-CoV-2. A systematic review and meta-analysis. JAMA Netw Open 2020;3(12):e2031756.doi: 10.1001/jamanetworkopen.2020.31756. 12.18.2  

14 Gao M, Yang L, Chen X, et al. A study on infectivity of asymptomatic SARS-CoV-2 carriers. Respir Med.     2020;169:106026. doi:10.1016/j.rmed.2020.106026

15 Brera G.R. The manifesto of Person-Centered Medicine. Medicine, Mind Adolescence,1999; Vol. XIV, n. 1-2:3-7

16 Brera G.R. . Person-centered Medicine and Medical Education in the Third Millennium (with the introduction of Iosef Seifert The seven aims of Medicine it.) Roma- Pisa: IEPI ;2001 (Italian)

17 Mezzich E.J. The Geneva Conferences and the emergence of the International Network for Person-centered Medicine. Journal of evaluation of Clinical Practice 2011;17(2):333-33

18 Brera G.R. Person-centered Medicine: Theory, Teaching, Research. Int.J.Pers. Cent.Med 2011; 1 (1):69-

19 Brera G.R   et al. Reliability and validity of Person-centered Medicine Clinical Method for a Person and People-Centered Care: a survey on 144 clinical reports of physicians prepared to apply Person-centered Clinical Method to adolescents from the Academic Year 1997 to 2002 at the Milan School of Medicine of the University Ambrosiana. Proceedings of the Vth Geneva Conference on Person-centered Medicine. 2012 April 30-May 2 Geneva, Person-centered Medicine International Network 2012.   DOI 10.13140/RG.2.1.4699.0568  

20 Brera G.R. The Person-centered Health Paradigm and its impact on health sciences.(Internet) Research Gate 2015 DOI:10.13140/RG 2.1.2594.1925 2015-05-21 T 15:42:05 UTC. Available from

https://www.researchgate.net/publication/277010325

21 WHO Person-centered Medicine and Medical Education. (internet) Geneva: WHO Symposium; 4 May 2011. WHO Available from

http://www.unambro.it/html/pdf/All_Symposium_Education_People_Centred_4May2011.pdf

22 Brera, G.R Person-Centered Medicine, and Person-Centered Clinical Method. Milano: Università Ambrosiana ed.: 2021

23 Brera G.R Sars-Cov-2 allostasis and the people and person-centered prevention. A new prevention strategy based on a people metabolic and immune shield for the pandemic shutdown. Part 1 The Sars-Cov 2 entry and COVID-19. Milan. Università Ambrosiana , 2021. ISBN: 9798530093906

24 Brera G.R . SARS-COV 2- allostasis and the people and person-centered prevention. Part 2 The Sars-Cov 2- induced immunosuppression and covid-19 anergy. Part 3 The antiviral metabolic allostasis and preventive immunostimulation - How to induce zero risk for covid-19. Milan: Ambrosiana University: 2021 ISBN

 

* Milan School of Medcine, World Health Committee, Comitato Sanitario Nazionale
** School of Medicine of the Minnaeapolis University, Scuola Medica di Milano,World Health Committee,Comitato Sanitario Mazionale

 

 

 







                          

  Il prof. Giuseppe R. Brera, autore del primo trattato pubblicato  e distribuito nel mondo sul SARS-COV 2  e il COVID-19, in rappresentanza del Comitato Sanitario Nazionale, della Scuola Medica di Milano , e della Società Italiana di Adolescentologia e Medicina dell'adolecenza, in concomitanza della petizione al Senato richiedente la sfiducia del Ministro: https://www.comitatosanitarionazionale.it/2021/04/30/petizione-al-senato-per-la-sfiducia-del-ministro-della-sanita-roberto-speranza/ ha chiesto le dimissioni immediate ed urgenti del Ministro della sanità per incompetenza a tutela della salute pubblica. La petizione, alla luce degli inconfutabili dati scientifici evidenziati nel trattato del prof.Brera, evidenzia come il Ministro  Speranza, con il sotto-segretario Sileri e i consiglieri Ricciardi, Brusaferri,Rezza,Locatelli abbia omesso la prevenzione secondaria-l'intervento preventivo sulla popolazione a rischio ( anziani con co-morbidità) che avrebbe potuto evitare la strage . La prevenzione  secondaria alla luce delle conoscenze scientifiche sulla SARS-COV 1 e una prevenzione primaria con una diversa filosofia basata sulla promozione e educazione della salute  della popolazione, finalizzata all'aumento dell'immunità naturale  e la terapia domiciliare, avrebbero potuto evitare la strage. Il ministro inoltre ha dato indicazioni, durante la pandemia, all'aborto frmacologico in day hospital, che oltre a uccidere un essere umano espone , per azione del misoprostolo, la donna a un blocco delle difese immunitarie, esponendole al COVID-19.    ( leggere Expertize)  Se l'analfabetismo medico-scientifico del ministro, porta la responabilità morale a chi ha eletto a tutela della salute della popolazione un ex assessore all'urbanistica laureato in scienze politiche, che nulla toglie alle sue responsabilità , non è giutificabile l'ignoranza scientifica dei collaboratori in particolare del sig.Ricciardi, suo consigliere, premiato da titolare del Vaticano, papa Francesco, già sotto indagine per l'induzione della vaccinazione esavalente, per azione della Società Italiana di Adolescentologia e Medicina dell'Adolescenza e per il conflitto d'interessi dello ex Direttore dello ISS Del Favero, membro del CDA fino al 2018 della Fondazione Smith-Kline, Italia, casa produttrice dei vaccini. Articolo redazionale ( Rodolfo di Hautecombe)   Bibliografia Person -Centered Medicine and Person -Centered Clinical Method- Practical results of the Medicine unitary paradigm and the COVID-19people and person-centered prevention theory ” 131 p. -132 references euro 35  ( e-book –  printed in distribution )   Sars-Cov-2 allostasis and the COVID-19  people and person-centered prevention-A new prevention strategy  based  on  the people’s metabolic and immune shield induction for the COVID-19 pandemic shutdown” TREATISE  632 p. - 1065 references.   ( 4 parts)  ( in distribution within 26 June  1st part "  Relativity of the virus entry") Only printed  35 euro (booking is possible)    Purchase orders and booking:  University Ambrosiana editorial department editorialdepartment@unambro.it  
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