An International Consensus Report on SARS-Cov-2, COVID-19, and the Immune System: An Orthomolecular View

International Society for Orthomolecular Medicine 

ISSN:0834-4825

Author(s): Michael J Gonzalez1,3‚4; Jorge R Miranda-Massari2‚4; Peter A McCullough5; Paul E Marik6; Pierre Kory7; Ryan Cole8; Geert Vanden Bossche9; Charles Simone10; Manuel Aparicio Alonso11; Ernesto Prieto Gratacos12; Atsuo Yanagisawa13; Richard Cheng14; Eduardo Insignares-Carrione15; Zhiyong Peng¹6; Robert J Rowen¹7; Teresa B Su¹7; Frank Shallenberger18; David Brownstein19; Thomas Levy20; Jorge L Cubrias21; Arturo O’Byrne Navia22; Arturo O’Byrne De Valdenebro23; Alex Vasquez24; Ron Hunninghake25; Andrew Saul26; Hugo Galindo27; Andreas L. Kalcker28; Mayca Gonzalez29; Luis A Bonilla-Soto30; María  Carrascal31; José W Rodriguez Zayas32; Efrain Olszewer33;  Michaël Friedman34; Miguel J Berdiel35; Norman O Gonzalez36; Jose Olalde37; Ines Alfaro38;  Roberto Ortiz39; Angie Perez40; Carlos H. Orozco Araya41; Luis Martinez42; Rosalina Valcarcel43; Sylvia Nuñez Fidalgo44; Fernando Pinto Floril45; Raul Morales Borges46; José R Rodriguez-Gomez47; José A Rodriguez-Robles48; Ramphis Diaz49; Carlos M Ricart50

1. University of Puerto Rico, Medical Sciences Campus, School of Public Health, San Juan PR.
2. University of Puerto Rico, Medical Sciences Campus, School of Pharmacy, San Juan PR.
3. Universidad Central del Caribe, School of Chiropractic, Bayamon, PR.
4. EDP University, Naturopathic Sciences Program, Hato Rey, PR.
5. Truth for Health Foundation, Tucson, AZ.
6. Front Line COVID-19 Critical Care Alliance (FLCCC) and Eastern Virginia Medical School, Department of Internal Medicine, VA.
7. Front Line COVID-19 Critical Care Alliance, Madison, WI.
8. Cole Diagnostics, Garden City, ID.
9. Independent virologist and vaccine expert, Cologne, Belgium.
10.  Simone Protective Cancer Center, Lawrenceville, NJ.
11. Centro Médico Jurica, Querétaro, México.
12. Precision Metabolic Oncology 12, Cambridge Science Park, Cambridge, England.
13. Japanese College of Intravenous Therapy, Tokyo, Japan; Japanese Society for Orthomolecular Medicine, Tokyo Japan: International Society for Orthomolecular Medicine, Toronto, Canada.
14. Cheng Integrative Health Center, Doctor’s Weight Loss Center, Columbia, SC.
15. Liechtensteiner Verein für Wissenschaft und Gesundheit, Liechtenstein, Switzerland.
16. Zhognnan Hospital, Wuhan University, Wuhan, Hubei, China.
17. Private Medical Practice, Santa Rosa, CA.
18. Private Medical Practice, Carson City, NV.
19. The Center for Holistic Medicine in West Bloomfield, MI.
20. Riordan Clinic, Wichita, KS.
21. Clinica Cellmedik, Santa Cruz de Tenerife, Spain.
22. Private practice, Bogota, Colombia.
23. Private practice in Clinical Immunology, Buenos Aires, Argentina.
24. International College of Human Nutrition and Functional Medicine, Barcelona, Spain.
25. Riordan Clinic, Wichita, KS.
26. Doctor Yourself.com, Rochester, NY.
27. Country Medical Center, Bogota, Colombia.
28. Independent Research in Biophysics, Berna, Switzerland.
29. Clínica Centro, Granada, Spain.
30. University of Puerto Rico, Medical Sciences Campus, School of Public Health, Department of Environmental Health, San Juan, PR.
31. Carrascal Clinic, Río Piedras, PR.
32. Cardiopulmonary Research Center, Guaynabo, PR;
33. Fundacao de apoio e pesquisa na area de saude-foundation for research in health and medicine Sao Paulo, Brasil.
34. Association for the Advancement of Restorative Medicine (AARM), Montpelier, VT.
35. Berdiel Clinic, Ponce PR.
36. Private Naturopathic Practice, Masters in Naturopathy Program, EDP University of Puerto Rico. San Juan, PR.
37. Centro Medico Regenerativo (CMR), Bayamón and Caguas PR.
38. Alpha Institute, Caguas, PR.
39. Holistic University, Department of Nutrition, Mexico City, Mexico.
40. ICEMI Medical Center, San Jose, Costa Rica, CA.
41. Private Medical Practice, San Jose, Costa Rica, CA.
42. Xanogene Clinic, San Juan, PR.
43. Private Medical Practice, San Juan, PR.
44. San Juan City Hospital, ER Dept., San Juan, PR.
45. Private Medical Practice, Quito, Ecuador.
46. Integrative Optimal Health of Puerto Rico, MB & R’s Enterprise, Ashford Institute of Hematology & Oncology, San Juan, PR.
47. Universidad Carlos Albizu, San Juan, PR.
48. Private Medical Practice, San Juan, PR, and Miami, FL.
49. Private Naturopathic Practice, San Juan, PR.
50. University of Puerto Rico Cayey Campus, Dept Biology, Cayey, PR.

Abstract

An unprecedented worldwide situation has taken place due to the pandemic related to the SARS- CoV-2 virus. In addition to a novel infectious disease and an unparalleled global response, COVID-19 also initiated an unparalleled course of action of vaccine research, production, testing, and distribution. The sense of urgency around combating the viral pandemic has led to public health decisions based on incomplete and non-evidence-based information. Many issues in relation to the virus SARS-Cov-2, the disease COVID-19, and the immune system need to be addressed, clarified, and put in a proper perspective in order to bring this pandemic to a more objective assessment.

This analysis may help manage its many challenges more efficiently, in addition, to providing a true opportunity to reduce complications, deaths, and iatrogenic side effects of either the infection or the vaccination, or both. The present consensus report has taken this necessary task to provide a common ground to effectively manage this global situation.

Chlorine Dioxide in COVID-19: Hypothesis about the Possible Mechanism of Molecular Action in SARS-CoV-2

Molecular and Genetic Medicine ISSN: 1747-0862

Eduardo Insignares-Carrione*, Blanca Bolano Gómez and Andreas Ludwig Kalcker

ISSN: 1747-0862

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Introduction

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It was first detected in the Chinese city of Wuhan (Hubei province) in December 2019. In three months it spread to basically all countries in the world, which is why the World Health Organization declared it a pandemic. (WHO, March 11, 2020).

There is no specific treatment; the main therapeutic measures are to relieve symptoms and maintain vital functions. Research to find an effective treatment began since the pandemic scale of the disease was verified. The central problem is that, eleven months after its official onset, an effective treatment for the disease is still unknown. In the absence of an effective treatment, we studied new therapeutic possibilities with the intention of finding an effective and safe treatment for COVID-19.

In accordance with the above, this research addresses current results and previous research adding the possible therapeutic action as a virucidal of chlorine dioxide in aqueous solution and without the presence of sodium chlorite using the concepts of translational medicine based on knowledge about the structure of the virus and the mechanism of action of chlorine dioxide in viruses, to propose a possible treatment of choice for COVID-19 [1,2].

Integrative Journal of Medical Sciences (ISSN: 2658-8218)

Enrique A. MartínezUniversidad Católica del Norte, Coquimbo, Chile

https://doi.org/10.15342/ijms.7.229

https://mbmj.org/index.php/ijms/article/view/229

ABSTRACT:

This article is written to encourage medical teams from all over the world to contact the COVID-19 patients already treated with Chlorine Dioxide in Solution (CDS), a water soluble gas. To contact also their medical teams accompanying the study cases in order to verify the actual health conditions of patients. Finally, the invitation is to question whether CDS should be tried in their respective local healthcare environments, as it is of low cost, it seems highly effective against all viral infections and it has almost no secondary effects.

Chlorine Dioxide as an Alternative Treatment for COVID-19

Journal of infectious disease and therapy.

Manuel Aparicio-Alonso, C. Domínguez-Sánchez, Marina Banuet-Martinez

ISSN: 2332-0877

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ABSTRACT:

To date, there is no effective prophylactic agent to prevent COVID-19. However, the development of symptoms similar to covid19 could be prevented with an aqueous solution of chlorine dioxide (ClO2). This retrospective study evaluated the effectiveness of an aqueous solution of ClO2 (CDS) as a prophylactic agent in 1,163 family members living with positive/suspected COVID19 patients. Prophylactic treatment consisted of 0.0003% chlorine dioxide solution (CDS) orally for at least fourteen days. Family members in whom no reports of the development of covid19-like symptoms were found in the medical history were considered successful cases. The efficacy of CDS in preventing covid19-like symptoms was 90.4% (1,051 of 1,163 relatives did not report any symptoms).

The comorbidities, sex and severity of the illness of the sick patient did not contribute to the development of symptoms similar to covid19 (P = 0.092, P = 0.351 and P = 0.574, respectively). However, older relatives were more likely to develop covid19-like symptoms (ORa = 4.22, P = 0.002). There was no evidence of alterations in blood parameters or in the QTc interval in relatives who consumed CDS. The recent findings regarding Chlorine Dioxide justify designing clinical trials to assess its efficacy for preventing SARS-CoV-2 infection.

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Nature communications chemistry selections (ISSN :2188-5044)

Jinsung Yang, Simon J. L. Petitjean, Melanie Koehler, Qingrong Zhang, Andra C. Dumitru, Wenzhang Chen, Sylvie Derclaye, Stéphane P. Vincent, Patrice Soumillion & David Alsteens

Abstract

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

International journal of multidisciplinary research and analysis

1Manuel Aparicio-Alonso,2 Carlos A. Domínguez-Sánchez, 3Marina Banuet-Martínez

(ISSN :2643-9875) https://doi.org/10.47191/ijmra/v4-i8-14

ABSTRACT:

The coronavirus disease 2019 (COVID19) has generated widespread healthcare concerns and has overburdened healthcare institutions. As the number of COVID19 patients recovers, so does the frequency of reports of COVID19-like symptoms following discharge. A telephone survey with standardized questions was undertaken in which participants were asked if they had had any of 25 possible sequelae after being diagnosed with COVID19 and treated with a Chlorine Dioxide Solution (CDS). One hundred sixty-one people completed the survey. We discovered that rising age is a risk factor (OR = 1.035, p = 0.028, 95% CI = 1.004-1.069), and the odds of having any symptoms in moderate patients is 0.077 compared to mild patients (P = 0.003). It was predicted that 64.6 percent of patients treated with CDS for SARS-CoV-2 infection experienced an average of 3.41 long-term effects. There were no variations in the number of sequelae reported by sex, age, COVID19 severity, or therapy method.

The five most prevalent manifestations of the 25 distinct long-term symptoms observed in this study were fatigue, hair loss, dyspnea, concentration problem, and sleep difficulties. In addition, individuals treated with multiple drugs (COVID19 conventional treatment plus a CDS) had 2.7 fewer cases of sequelae, and patients treated exclusively with CDS had 6.14 fewer incidences of long-term effects. People who get a CDS are 19% less likely to experience long-term health effects than patients who receive standard COVID19 therapy. According to the findings of this study, patients who receive a CDS have a reduced probability of developing sequelae. Furthermore, the incidence of long-term effects is lower in individuals treated exclusively with a CDS. The recent findings involving Chlorine Dioxide support the development of clinical studies to evaluate its efficacy in preventing the development of COVID19 long-term effects.

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in Relatives Living with COVID19 Patients

INTERNATIONAL JOURNAL OF MULTIDISCIPLINARY RESEARCH AND ANALYSIS

1Manuel Aparicio-Alonso, 2Carlos A. Domínguez-Sánchez, 3Marina Banuet-Martínez

ISSN: 2643-9875

ABSTRACT:

To date, there is no effective prophylactic agent to prevent COVID-19. However, the development of symptoms similar to covid19 could be prevented with an aqueous solution of chlorine dioxide (ClO2). This retrospective study evaluated the effectiveness of an aqueous solution of ClO2 (CDS) as a prophylactic agent in 1,163 family members living with positive/suspected COVID19 patients. Prophylactic treatment consisted of 0.0003% chlorine dioxide solution (CDS) orally for at least fourteen days. Family members in whom no reports of the development of covid19-like symptoms were found in the medical history were considered successful cases.

The efficacy of CDS in preventing covid19-like symptoms was 90.4% (1,051 of 1,163 relatives did not report any symptoms). The comorbidities, sex and severity of the illness of the sick patient did not contribute to the development of symptoms similar to covid19 (P = 0.092, P = 0.351 and P = 0.574, respectively). However, older relatives were more likely to develop covid19-like symptoms (ORa = 4.22, P = 0.002). There was no evidence of alterations in blood parameters or in the QTc interval in relatives who consumed CDS. The recent findings regarding Chlorine Dioxide justify designing clinical trials to assess its efficacy for preventing SARS-CoV-2 infection.

Comparative study of hyperpure chlorine dioxide with two other irrigants regarding the viability of periodontal ligament stem cells

Orsolya Láng, Krisztina S. Nagy, Julia Láng, Katalin Perczel-Kovách, Anna Herczegh, Zsolt Lohinai, Gábor Varga & László Kőhidai

Springer (ISSN: 2627-8626)

Abstract

Objectives: Periodontal ligament stem cells (PDLSCs) have an underlined significance as their high proliferative capacity and multipotent differentiation provide an important therapeutic potential. The integrity of these cells is frequently disturbed by the routinely used irrigative compounds applied as periodontal or endodontic disinfectants (e.g., hydrogen peroxide (H2O2) and chlorhexidine (CHX)). Our objectives were (i) to monitor the cytotoxic effect of a novel dental irrigative compound, chlorine dioxide (ClO2), compared to two traditional agents (H2O2, CHX) on PDLSCs and (ii) to test whether the aging factor of PDLSC cultures determines cellular responsiveness to the chemicals tested.

Controlled Clinical Evaluations of Chlorine Dioxide, Chlorite and Chlorate in Man

Environmental Health Perspectives (EHP)

J R Lubbers, S Chauan, and J R Bianchine

(ISSN: 1542-6351)

Abstract

To assess the relative safety of chronically administered chlorine water disinfectants in man, a controlled study was undertaken. The clinical evaluation was conducted in the three phases common to investigational drug studies. Phase I, a rising dose tolerance investigation, examined the acute effects of progressively increasing single doses of chlorine disinfectants to normal healthy adult male volunteers. Phase II considered the impact on normal subjects of daily ingestion of the disinfectants at a concentration of 5 mg/l. for twelve consecutive weeks. Persons with a low level of glucose-6-phosphate dehydrogenase may be expected to be especially susceptible to oxidative stress; therefore, in Phase III, chlorite at a concentration of 5 mg/l. was administered daily for twelve consecutive weeks to a small group of potentially at-risk glucose-6-phosphate dehydrogenase-deficient subjects.

Physiological impact was assessed by evaluation of a battery of qualitative and quantitative tests. The three phases of this controlled double-blind clinical evaluation of chlorine dioxide and its potential metabolites in human male volunteer subjects were completed uneventfully. There were no obvious undesirable clinical sequellae noted by any of the participating subjects or by the observing medical team. In several cases, statistically significant trends in certain biochemical or physiological parameters were associated with treatment; however, none of these trends was judged to have physiological consequence. One cannot rule out the possibility that, over a longer treatment period, these trends might indeed achieve proportions of clinical importance. However, by the absence of detrimental physiological responses within the limits of the study, the relative safety of oral ingestion of chlorine dioxide and its metabolites, chlorite and chlorate, was demonstrated.

Denaturation of Protein by Chlorine Dioxide: Oxidative Modification of Tryptophan and Tyrosine Residues

Biochemistry ACS PUB

Norio Ogata

(ISSN :0922-3444).

Abstract

Oxychlorine compounds, such as hypochlorous acid (HOCl) and chlorine dioxide (ClO2), have potent antimicrobial activity. Although the biochemical mechanism of the antimicrobial activity of HOCl has been extensively investigated, little is known about that of ClO2. Using bovine serum albumin and glucose-6-phosphate dehydrogenase of Saccharomyces cerevisiae as model proteins, here I demonstrate that the antimicrobial activity of ClO2 is attributable primarily to its protein-denaturing activity. By solubility analysis, circular dichroism spectroscopy, differential scanning calorimetry, and measurement of enzymatic activity, I demonstrate that protein is rapidly denatured by ClO2 with a concomitant decrease in the concentration of ClO2 in the reaction mixture. Circular dichroism spectra of the ClO2-treated proteins show a change in ellipticity at 220 nm, indicating a decrease in α-helical content. Differential scanning calorimetry shows that transition temperature and endothermic transition enthalpy of heat-induced unfolding decrease in the ClO2-treated protein.

The enzymatic activity of glucose-6-phosphate dehydrogenase decreases to 10% within 15 s of treatment with 10 μM ClO2. Elemental analyses show that oxygen, but not chlorine, atoms are incorporated in the ClO2-treated protein, providing direct evidence that protein is oxidized by ClO2. Furthermore, mass spectrometry and nuclear magnetic resonance spectroscopy show that tryptophan residues become N-formylkynurenine and tyrosine residues become 3,4-dihydroxyphenylalanine (DOPA) or 2,4,5-trihydroxyphenylalanine (TOPA) in the ClO2-treated proteins. Taking these results together, I conclude that microbes are inactivated by ClO2 owing to denaturation of constituent proteins critical to their integrity and/or function, and that this denaturation is caused primarily by covalent oxidative modification of their tryptophan and tyrosine residues.

Effects of Chlorine Dioxide on Oral Hygiene – A Systematic Review and Meta-analysis

Author(s): Beáta Kerémi, Katalin Márta, Kornélia Farkas, László M. Czumbel, Barbara Tóth, Zsolt Szakács, Dezső Csupor, József Czimmer, Zoltán Rumbus, Péter Révész, Adrienn Németh, Gábor Gerber, Péter Hegyi and Gábor Varga*

DOI: 10.2174/1381612826666200515134450

Abstract

Background: Effective and selective oral rinses are required in the daily medical and dental practice. Currently mouthwashes used have substantial side effects.

Objectives: Our aim was to evaluate the efficacy of chlorine dioxide-containing mouthwashes in comparison with other previously established mouth rinses in healthy adults using oral hygiene indices.

Methods: This work was registered in PROSPERO (CRD42018099059) and carried out using multiple databases and reported according to the PRISMA statement. The search terms used were “chlorine dioxide” AND “oral”, and only randomised controlled trials (RCTs) were included. The primary outcome was the alteration of the plaque index (PI), while the secondary outcomes were the gingival index (GI) and bacterial counts. For the risk of bias assessment, the Cochrane Risk of Bias Tool was used. Statistical analysis for data heterogeneity was performed by Q-value and I2-tests.

Results: 364 articles were found in the databases. After the selection process, only five RCTs were eligible for meta-analysis. Data heterogeneity was low. There were no statistical differences in effectiveness between chlorine dioxide and other effective mouth rinses in PI (0.720±0.119 vs 0.745±0.131; 95%; confidence intervals (CIs): 0.487-0.952 vs 0.489-1.001, respectively) and GI (0.712±0.130 vs 0.745±0.131; 95% CIs: 0.457–0.967 vs 0.489– 1.001, respectively) and also in bacterial counts.

Conclusion: Chlorine dioxide reduces both plaque and gingival indices and bacterial counts in the oral cavity similar to other routinely used oral rinses, however, the evidence supporting this outcome is very limited. Therefore, further large scale RCTs are needed to decrease the risk of bias.

Kinetics and Mechanisms of Chlorine Dioxide and Chlorite Oxidations of Cysteine and Glutathione

Inorg. Chem. ACS PUB

Ana Ison, Ihab N. Odeh, and Dale W. Margerum

(ISSN: 1044-5099)

Abstract

Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first-order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7−9.5 at 25.0 °C. The rates of chlorine dioxide decay are first order in both ClO2 and CSH concentrations and increase rapidly as the pH increases. The proposed mechanism is an electron transfer from CS- to ClO2(1.03 × 108 M-1 s-1) with a subsequent rapid reaction of the CS• radical and a second ClO2 to form a cysteinyl−ClO2 adduct (CSOClO). This highly reactive adduct decays via two pathways. In acidic solutions, it hydrolyzes to give CSO2H (sulfinic acid) and HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH increases, the (CSOClO) adduct reacts with CS- by a second pathway to form cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from 6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH.

The ClO2 oxidation of glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 × 108 M-1 s-1. The reaction of ClO2 with CSSC is 7 orders of magnitude slower than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl-. The reaction products are CSSC and CSO3H with a pH-dependent distribution similar to the ClO2/CSH system.

The 40–80 nt Region in the 50 -NCR of Genome Is a Critical Target for Inactivating Poliovirus by Chlorine Dioxide

M E Alvarez, R T O’Brien

Journal of Medical Virology

(ISSN :1096-9071)

Abstract

Chlorine dioxide and iodine inactivated poliovirus more efficiently at pH 10.0 than at pH 6.0. Sedimentation analyses of viruses inactivated by chlorine dioxide and iodine at pH 10.9 showed that viral RNA separated from the capsids, resulting in the conversion of virions from 156S structures to 80S particles. The RNAs release from both chlorine dioxide- and iodine-inactivated viruses cosedimented with intact 35S viral RNA. Both chlorine dioxide and iodine reacted with the capsid proteins of poliovirus and changed the pI from pH 7.0 to pH 5.8. However, the mechanisms of inactivation of poliovirus by chlorine dioxide and iodine were found to differ. Iodine inactivated viruses by impairing their ability to adsorb to HeLa cells, whereas chlorine dioxide-inactivated viruses showed a reduced incorporation of [14C]uridine into new viral RNA. We concluded, then, that chlorine dioxide inactivated poliovirus by reacting with the viral RNA and impairing the ability of the viral genome to act as a template for RNA synthesis.

Kinetics and Mechanism of Bacterial Disinfection by Chlorine Dioxide

American Society for Microbiology

Melvin A. Benarde, W. Brewster Snow, Vincent P. Olivieri, Burton Davidson

(ISSN: 0569-7603)

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Abstract

Survival data are presented for a fecal strain of Escherichia coli exposed to three concentrations of chlorine dioxide at four temperatures. Chick’s first-order reaction equation is generalized to a pseudo nth-order model. Nonlinear least squares curve-fitting of the survival data to the nth order model was performed on an analogue computer. The data were observed to follow fractional order kinetics with respect to survival concentration, with an apparent activation energy of 12,000 cal/mole. Initial experiments support the thesis that the mechanism of chlorine dioxide kill occurs via disruption of protein synthesis.

Study on the resistance of severe acute respiratory syndrome-associated coronavirus

Elsevier

(ISSN :0922-3444)

Xin-Wei Wang a, Jin-Song Li b, Min Jin a, Bei Zhen b, Qing-Xin Kong a, Nong Song a, Wen-Jun Xiao b, Jing Yin a, Wei Wei b, Gui-Jie Wang b, Bing-yin Si b, Bao-Zhong Guo b, Chao Liu c, Guo-Rong Ou a, Min-Nian Wang b, Tong-Yu Fang d, Fu-Huan Chao a, Jun-Wen Li 

Abstract

In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20 °C. However, at 4 °C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5 mg/L for chlorine or 2.19 mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.

Protective effect of low-concentration chlorine dioxide

Journal of General Virology

Norio Ogata1, Takashi Shibata1

(ISSN :1465-2099)

ABSTRACT 

Influenza virus infection is one of the major causes of human morbidity and mortality. Between humans, this virus spreads mostly via aerosols excreted from the respiratory system. Current means of prevention of influenza virus infection are not entirely satisfactory because of their limited efficacy. Safe and effective preventive measures against pandemic influenza are greatly needed. We demonstrate that infection of mice induced by aerosols of influenza A virus was prevented by chlorine dioxide (ClO2) gas at an extremely low concentration (below the long-term permissible exposure level to humans, namely 0.1 p.p.m.). Mice in semi-closed cages were exposed to aerosols of influenza A virus (1 LD50) and ClO2 gas (0.03 p.p.m.) simultaneously for 15 min.

Three days after exposure, pulmonary virus titre (TCID50) was 102.6±1.5 in five mice treated with ClO2, whilst it was 106.7±0.2 in five mice that had not been treated (P=0.003). Cumulative mortality after 16 days was 0/10 mice treated with ClO2 and 7/10 mice that had not been treated (P=0.002). In in vitro experiments, ClO₂ denatured viral envelope proteins (haemagglutinin and neuraminidase) that are indispensable for infectivity of the virus, and abolished infectivity. Taken together, we conclude that ClO2 gas is effective at preventing aerosol-induced influenza virus infection in mice by denaturing viral envelope proteins at a concentration well below the permissible exposure level to humans. ClO2 gas could therefore be useful as a preventive means against influenza in places of human activity without necessitating evacuation.

Can nasal irrigation with chlorine dioxide be considered as a potential alternative therapy for respiratory infectious diseases? The example of COVID-19

BioScience Trends

Jing Cao, Yirong Shi, Min Wen, Yuanyuan Peng, Qiqi Miao, Xiaoning Liu, Mingbin Zheng, Tetsuya Asakawa, Hongzhou Lu

 https://doi.org/10.5582/bst.2022.01495

Abstract

Chlorine dioxide (ClO2) is a high-level disinfectant that is safe and widely used for sterilization. Due to the limitations on preparing a stable solution, direct use of ClO2 in the human body is limited. Nasal irrigation is an alternative therapy used to treat respiratory infectious diseases. This study briefly summarizes the available evidence regarding the safety/efficacy of directly using ClO2 on the human body as well as the approach of nasal irrigation to treat COVID-19. Based on the available information, as well as a preliminary experiment that comprehensively evaluated the efficacy and safety of ClO2, 25-50 ppm was deemed to be an appropriate concentration of ClO2 for nasal irrigation to treat COVID-19. This finding requires further verification. Nasal irrigation with ClO2 can be considered as a potential alternative therapy to treat respiratory infectious diseases, and COVID-19 in particular.

Infection Prevention and Tissue Repair in Skin Lesions Using Treatments Based on a Chlorine Dioxide Solution: Case Studies

Literaturepublishers

Aparicio-Alonso M

Abstract 

Optimal regeneration of skin lesions needs to ensure protection against opportunistic infections that may hinder the healing process or increase the risk of infection. The use of antibiotics to avoid infection can, in some cases, interfere with tissue regeneration, and often fails due to resistant bacterial strains. Thus, there is a need to expand the arsenal of safe and effective treatment options available. Here, we document the prevention of infections and tissue repair in skin lesions using treatments based on a chlorine dioxide solution. We document four case reports, that include an abdominal burn by a chemical agent, a palpebral burn by extreme heat, limb ulceration due to vascular insufficiency, and a melanoma of the scalp. All lesions were treated topically with a chlorine dioxide solution, and systemically when necessary, according to previously proposed protocols.

All four patients showed complete dermal regeneration, with aesthetic results, no side effects or any evidence of adverse effects or interactions with the concomitant treatments used. The results constitute evidence that a topical or systemic solution of chlorine dioxide is safe as an antiseptic treatment in the adequate and swift resolution of skin lesions.

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeutic approach

Elservier

Laurent Schwartz a, Manuel Aparicio-Alonso b, Marc Henry c, Miroslav Radman d, Romain Attal e, Ashraf Bakkar f

https://doi.org/10.1016/j.freeradbiomed.2023.05.034

Abstract

We previously demonstrated that most diseases display a form of anabolism due to mitochondrial impairment: in cancer, a daughter cell is formed; in Alzheimer’s disease, amyloid plaques; in inflammation cytokines and lymphokines.

The infection by Covid-19 follows a similar pattern. Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction. This unrelenting anabolism leads to the cytokine storm, chronic fatigue, chronic inflammation or neurodegenerative diseases. Drugs such as Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism. Similarly, coMeBining Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism.

Graphical abstract

Chlorine dioxide is a more potent antiviral agent against SARS-CoV-2 than sodium hypochlorite

Elservier

N. Hatanaka , B. Xu , M. Yasugi , H. Morino , H. Tagishi , T. Miura , T. Shibata , S. Yamasaki

Summary

Background

A new coronavirus (SARS-CoV-2) abruptly emerged in Wuhan, China, in 2019 and rapidly spread globally to cause the COVID-19 pandemic.

Aim

To examine the anti-SARS-CoV-2 activity of the potent disinfectant Cleverin, the major disinfecting component of which is chlorine dioxide (ClO2); and to compare the results with that of sodium hypochlorite in the presence or absence of 0.5% or 1.0% foetal bovine serum (FBS).

Methods

Concentrated SARS-CoV-2 viruses were treated with various concentrations of ClO2 and sodium hypochlorite and 50% tissue culture infective dose was calcurated to evaluate the antiviral activity of each chemical.

Findings

When SARS-CoV-2 viruses were treated with 0.8 ppm ClO2 or sodium hypochlorite, viral titre was decreased only by 1 log10 TCID50/mL in 3 min. However, the viral titre was decreased by more than 4 log10 TCID50/mL when treated with 80 ppm of each chemical for 10 s regardless of presence or absence of FBS. It should be emphasized that treatment with 24 ppm of ClO2 inactivated more than 99.99% SARS-CoV-2 within 10 s or 99.99% SARS-CoV-2 in 1 min in the presence of 0.5% or 1.0% FBS, respectively. By contrast, 24 ppm of sodium hypochlorite inactivated only 99% or 90% SARS-CoV-2 in 3 min under similar conditions. Notably, except for ClO2, the other components of Cleverin such as sodium chlorite, decaglycerol monolaurate, and silicone showed no significant antiviral activity.

Conclusion

Altogether, the results strongly suggest that although ClO2 and sodium hypochlorite are strong antiviral agents in absence of organic matter but in presence of organic matter, ClO2 is a more potent antiviral agent against SARS-CoV-2 than sodium hypochlorite.

Author:

• George Georgiou

Title of the Study:

• Eradication of Borrelia burgdorferi in vitro using chlorine dioxide: A novel approach.

Source:

• Archives of Medical Research, [online] 10(11)

DOI:

• Enlace DOI: https://doi.org/10.18103/mra.v10i11.3279

Summary of the Study: Summary:.

• Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent tick-borne disease in the world today and has become a serious public health problem over the past decade, despite decades of efforts by various healthcare professionals. Conventional treatment of Lyme disease is the use of various antibiotics, but relapses often occur when antibiotics are discontinued. There are several reasons why this relapse may occur, given that B. burgdorferi is a pleomorphic microorganism that can convert from vegetative spirochete to a variety of different round bodies and biofilm colonies. Therefore, there is an urgent need for novel approaches that can eliminate all of these different morphologies. This has been a challenge for many healthcare professionals around the world, not to mention the suffering of many affected individuals.
  
  
• In this study, we tested the in vitro efficacy of chlorine dioxide (CD) at different concentrations against B. burgdorferi using fluorescent and darkfield microscopy combined with Live-or-Dye staining methods. Our experiments demonstrated that it is possible to completely eradicate all forms of B. burgdorferi at specific concentrations of chlorine dioxide. Our extensive research has shown that chlorine dioxide can be used for the eradication of B. burgdorferi morphologies. At certain concentrations of chlorine dioxide above 2 ppm, Borrelia morphologies appear to be eradicated, as there is no motility of either spirochetes or round bodies, only biofilms are visible. However, upon incubation again for another 7 days, Borrelia became motile again as they emerged from the biofilms. Therefore, we decided to perform each experiment with what we call Regrowth Kill Test (RKT) by incubating the initial sample with the CD in an incubator at 37 degrees Celsius in the Campypack for 7 days. Apparently, the biofilms that form rapidly as soon as the CD is added in the initial experiment ruptured and released small spirochetes and round bodies of different morphologies. After numerous RKT experiments, it was determined that the concentration that produced almost complete disinfection of spirochetes as well as round bodies was 30 ppm CD.

Authors: Jia Wei Yeap, Simran Kaur, Fangfei Lou, Erin DiCaprio, Mark Morgan, Richard Linton, Jianrong Li Publication Details: Jia Wei Yeap, Simran Kaur, Fangfei Lou, Erin DiCaprio, Mark Morgan, Richard Linton, Jianrong Li Publication Details:.

• Study Title: Inactivation of Murine Norovirus on a Stainless Steel Surface by Chlorine Dioxide Gas
• DOI: https://doi.org/10.1128/AEM.02489-15
• Journal: Applied and Environmental Microbiology, Vol. 82, No. 1
• Year of Publication: Not specified in the information provided.

Study Abstract: This study focuses on the inactivation of murine norovirus 1 (MNV-1), a surrogate for human norovirus, on stainless steel (SS) surfaces using chlorine dioxide gas (ClO2). Key findings include:

• Acute gastroenteritis caused by human norovirus is a major public health problem, especially in high-risk foods such as fresh produce and seafood.
• Food contact surfaces can also harbor norovirus if exposed to fecal contamination, aerosolized vomit, or infected food handlers.
• Chlorine dioxide gas (ClO2) is used as a decontaminating agent in food processing plants due to its strong oxidizing capacity.
• The objective of the study was to determine the kinetics and mechanism of MNV-1 inactivation on stainless steel coupons by ClO2 gas.
• MNV-1 was inoculated onto stainless steel coupons, and samples were treated with ClO2 gas at different concentrations and times.
• Treatment with ClO2 gas at 2 mg/liter for 5 minutes and at 2.5 mg/liter for 2 minutes resulted in at least a 3 log reduction in MNV-1.
• At a concentration of 4 mg/liter, no infectious virus was recovered even after 1 minute of treatment.
• The mechanism of inactivation by ClO2 gas included degradation of viral protein, alteration of viral structure, and degradation of viral genomic RNA.

In summary, treatment with ClO2 gas is identified as an effective method to inactivate a human norovirus surrogate on stainless steel surfaces.

Authors:

• Orsolya Láng
• Krisztina S. Nagy
• Julia Láng
• Katalin Perczel-Kovách
• Anna Herczegh
• Zsolt Lohinai
• Gábor Varga
• László Kőhidai

Key Dates:

• Received: June 16, 2020
• Accepted: October 1, 2020

DOI:

• Enlace DOI: https://doi.org/10.1007/s00784-020-03618-5

Summary of the Study: Objectives:.

• Periodontal ligament stem cells (PDLSCs) have an important significance as their high proliferative capacity and multipotent differentiation provide important therapeutic potential.
• The integrity of these cells is frequently disrupted by irrigant compounds commonly used as periodontal or endodontic disinfectants (e.g., hydrogen peroxide [H2O2] and chlorhexidine [CHX]).
• Our objectives were (i) to monitor the cytotoxic effect of a new dental irrigation compound, chlorine dioxide (ClO2), in comparison with two traditional agents (H2O2, CHX) on PDLSCs and (ii) to test whether the aging factor of PDLSC cultures determines the cellular responsiveness to the tested chemicals.

Methods:

• Impedimetry (concentration-response study), WST-1 assays (WST = water-soluble tetrazolium salt) and morphological analysis were performed to measure changes in cell viability induced by the 3 disinfectants.
• Immunocytochemistry of stem cell markers (STRO-1, CD90 and CD105) measured the induced mesenchymal characteristics.

Results:

• Cell viability experiments showed that the application of ClO2 does not cause a significant decrease in the viability of PDLSCs at the concentrations used to kill microbes.
• In contrast, traditional irrigants, H2O2 and CHX are highly toxic to PDLSCs.
• Aging of PDLSC cultures (passages 3 vs. 7) has characteristic effects on their responsiveness to these agents, as increased expression of mesenchymal stem cell markers becomes decreased.

Conclusions and clinical relevance:

• While the active ingredients of mouthwashes (H2O2, CHX) applied in endodontic or periodontitis treatment have a severe toxic effect on PDLSCs, the novel hyperpure ClO2 is less toxic, providing an environment that favors tooth structure regenerations during disinfectant interventions.

Manuel Aparicio-Alonso

Centro Médico Jurica, Medical Direction and Healthcare Responsibility, Querétaro, Mexico.

Link: https://orcid.org/0000-0002-0188-9871
Verónica Torres-Solórzano
Universidad Autónoma de Querétaro, Unit for Basic and Applied Microbiology. Querétaro, Mexico.

DOI: https://doi.org/10.56294/saludcyt2024699

Summary:

Chlorine dioxide is a potent and affordable oxidizing agent that has demonstrated anticancer activity both in vitro and in vivo. Its proposed mechanism is related to the release of free radicals, which alter the delicate oxidative balance of cancer cells. In this clinical case, a patient voluntarily chose compassionate chlorine dioxide therapy over conventional chemotherapy and immunotherapy because of side effects and uncertainty about survival prognosis. The concentration of the chlorine dioxide solution was 1/100 times lower than the LOAEL threshold, which ensured that the patient’s health was not compromised. This is the first follow-up in a patient diagnosed with metastatic prostate cancer, which showed tumor shrinkage at sites distant from the primary tumor without side effects. This preliminary observation suggests that chlorine dioxide and its free radicals could be potential mediators of an anticancer response. However, it is imperative to emphasize the importance of conducting rigorous clinical trials to validate these initial findings.

Introduction: cancer is a fermentation process.

In the early 1920s, Otto Warburg demonstrated a unique feature of cancer cells, namely increased glucose uptake and lactic acid secretion by cancer cells, even in the presence of oxygen (i.e., the aerobic glycolytic phenotype) ^1,2 . This aerobic fermentation is the signature of cancer ³ . Warburg also noted a concomitant decrease in the number of mitochondria (grana),sup>4

. In normal, differentiated cells, the yield of one molecule of glucose is 34 ATP. ATP is derived primarily from oxidative phosphorylation occurring in the mitochondria ^5,6 . In the absence of mitochondria, the energy yield drops to two molecules of ATP per molecule of glucose ^5,6 . As Warburg stated in the 1920s, in cancer cells there is a decreased efficiency of the mitochondria, resulting in a lower yield. Despite increased glucose uptake, there is a 50% drop in ATP level in human colon cancer cells compared to adjacent benign cells ⁷ . This decrease in ATP is a consequence of impaired oxidative phosphorylation ^6-9 .

To compensate for the decrease in energy yield, the cell increases its glucose uptake ^7,10 . The decrease in mitochondrial activity has many consequences, one of which is the increased secretion of lactic acid and another is the activation of the pentose phosphate pathway (PPP). Another consequence is the activation of glutaminolysis, necessary for the synthesis of nucleic acids ^6-9 .

Activation of the pentose phosphate pathway results from an increase in glucose uptake with a concomitant hindrance downstream of the pentose phosphate shunt, most likely at the level of pyruvate dehydrogenase and/or pyruvate kinase ^2,6,11 . Increased flux in the pentose phosphate pathway results:

– A shift towards anabolism due to increased NADPH synthesis which plays a crucial role in the NADPH/NADP+ ratio that determines the redox state of the cell by scavenging reactive oxygen species (ROS) and thus prevents cell death and controls cell fate ^7,11 .

– The shift to the pentose pathway also results in the production of ribose-5-phosphate, necessary for the synthesis of nucleic acids ⁵ .

Another important consequence of the mitochondrial defect is intracellular alkalosis ⁷ . Tumors exhibit an “inverted” pH gradient with a constitutively increased intracellular pH that is higher than the extracellular pH. This gradient enables cancer progression by promoting proliferation, apoptosis evasion, metabolic adaptation, migration and invasion ^12-15 .

There is evidence that an acidic extracellular pH promotes invasiveness and metastatic behavior in several tumor models14,16, activation of proteolytic enzymes and matrix destruction ^17-19 .

In normal cells, the intracellular pH (pHi) oscillates during the cell cycle between 6.8 and 7.3 ⁷ . The pH oscillation during the cell cycle coincides with the value of histone decompaction, RNA polymerase activation, DNA polymerase activation and DNA compaction prior to mitosis ^7.11 .

The intracellular pH of cancer cells has been less well studied. During the cell cycle it ranges from 7.2 to 7.5. Intracellular alkalosis is probably a consequence of decreased oxidative phosphorylation resulting in decreased carbon dioxide (CO2 ) secretion and CO2 reacts with water to create carbonic acid. Cell transformation or enhanced cancer cell division and resistance to chemotherapy are associated with a more alkaline pHi ^20-23 .

The Warburg effect may be a direct consequence of oncogene activation ⁶ . Infection with an oncogenic virus or exposure to a carcinogen inhibits mitochondrial function and causes the Warburg effect ^24-29 .

Download: https://www.researchgate.net/publication/321315675_Chlorine_dioxide_as_a_possible_adjunct_to_metabolic_treatment

Summary:

Antimicrobial-resistant infections (AMR) claim at least 50,000 lives a year in Europe and the United States alone.
every year in Europe and the United States, and hundreds of thousands more in other areas of the world. In 15 European countries, more than 10% of Staphylococcus aureus infections are caused by methicillin-resistant strains (MRSA), and in several of these countries resistance rates are approaching 50%. countries record resistance rates approaching 50%.1 Moreover, while the number of antibiotic-resistant infections is increasing, the number of new antibiotics is decreasing.1,2 Therefore, it is imperative that new treatments for antibiotic-resistant infections be developed. Therefore, it is imperative to search for new treatments against AMR.

This is the premise of this research: to use natural substances to eradicate MRSA that do not create further resistance.

Chlorine dioxide used in vitro, has been our main target of this research, as it was the most effective, compared to other natural substances tested. effective, compared to other natural substances tested.

Link: https://medcraveonline.com/JBMOA/JBMOA-09-00306.pdf

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Mancera Andrade, Jose. (2014). “Effect of chlorine dioxide in the prevention of adhesion formation in pelvic surgery.” (Specialization degree work). National Autonomous University of Mexico, Mexico. Retrieved from https://repositorio.unam.mx/contenidos/380887

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Link: https://repositorio.unam.mx/contenidos/efecto-del-dioxido-de-cloro-en-la-prevencion-de-la-formacion-de-adherencias-en-cirugia-pelvica-380887?c=4AXAad&d=false&q=*:*&i=1&v=1&t=search_0&as=0

Objective: To evaluate the clinical and microbiological efficacy of chlorine dioxide (ClO2) as a topical antiseptic for the treatment of chronic atrophic candidiasis in geriatric patients.

Participants: Thirty patients with chronic atrophic candidiasis.

Methods: Patients were instructed to rinse their mouths with 0.8% ClO2 mouthwash (DioxiDent) twice daily for one minute and to soak their dentures overnight in ClO2 for 10 days. Patients were evaluated clinically and microbiologically at baseline and after 10 days, and any significant side effects were recorded. The clinical appearance of the oral soft tissues was graded on a scale of 0 to 3 (0 indicating no clinical signs, 1 indicating involvement of <25% of the palatal mucosa, 2 indicating involvement of 25-50% of the palatal mucosa and 3 indicating marked erythema affecting >50% of the palatal mucosa). Microbiological tests were performed to determine the number of colony-forming units (CFU) of Candida albicans.

Results: ClO₂ significantly improved clinical appearance and microbial count (p < 0.001) after treatment, with no significant side effects. Results showed a marked improvement in clinical appearance of tissues after 10 days, with complete resolution in most cases.Total CFU/ml ranged from 15,000 to 53,000 at baseline and was reduced to < o = 500 after 10 days of treatment (p < 0.001). The mean clinical score was 2.50 at baseline and was reduced to 0.17 after 10 days of treatment (p < 0.001).

Conclusions: Within the limitations of this pilot study, the efficacy of topical chlorine dioxide (0.8%) in the treatment of chronic atrophic candidiasis was demonstrated. ClO2 provided a safe and clinically effective option in the treatment of chronic atrophic candidiasis.

Link: https://pubmed.ncbi.nlm.nih.gov/15218896/