MASTER-SPECIALIZZAZIONI-PERFEZIONAMENTO-RICERCA

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its form,[8]  found epidemiological and clinical evidence that confirm the theoretical assumptions [9] [10]  with many unpublished records.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

©Giuseppe R.Brera 2022

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