by Dr. Jose Baeza-Noci1, Dr. Lamberto Re2, Dr. Silvia Menendez2
1 WFOT Vice-President; 2 WFOT Scientific Advisory Committee
SARS-Cov2 has a mean incubation period of 5 days, although it can reach up to 2 weeks’.
Infected patients evolve differently and extreme cases die after 10 days of being infected. Most patients ask for medical help after 5 days of suffering a catarrhal syndrome that worsens. They usually remain in-hospital for 3 weeks before discharge but according to age and concomitant pathology, 10% go to ICU. The prognosis there is also related with age and concomitant diseases as indicated by WHO.
Ozone therapy possible role in COVID-19.
Bocci and cols. tested in vivo effects of ozone in patients with different infections and discovered the following facts:
1- Ozone improves lung and peripheral tissue oxygenation and gases exchange because of peripheral vase-dilatation mediated by nitrosotyols and enhanced glucolysis in erythrocytes that produce more ATP and secondary higher 2,3-DPG levels (Bohr effect) and more elasticity because an optimal functioning of Na/K+ membrane pump.
2- Ozone modulates the NRF2 and this produces two effects. First, normalize the redox balance through the increase in antioxidants in cytoplasma, mitochondria and finally, plasma, mainly glutatione peroxidase, but also glutatione reductase, NADPH and SOD. Second ,induces the production of HO-1, a protective enzyme, together heat-shock proteins like HSP60, HSP70 and HSP90. Third , activates the NFKbeta that modulates the production of proinflammatory interleukines in inflammated tissues. All three effects contribute to restore the normal functioning of the inflammated tissues and decrease the amount of plasma interleukines.
Many pre-clinical papers have confirmed these results, but there are also clinical studies that have confirmed these facts:
– Hernandez-Rosales and cols. in 2005 reported the improvement of asthma patients in both, analytical tests and respiratory function after ozone systemic treatment and also compare the effect of different doses of ozone.
– Borrelli and Bocci in 2014 confirmed these results in other group of chronic obstructive pulmonary disease (COPD) patients.
– Vinnik and cols. proved in 2015 the decrease in IL6 and other pro-inflammatorio citokynes in diabetes mellitus patients treated with systemic ozone.
– Delgado-Roche and cols. also published in 2017 the same findings in multiple sclerosis patients.
– Tong N and cols. published in 2018 a great decrease in IL6 in patients suffering lumbar disc herniation and treated with systemic ozone.
Many papers have been published about the improvement of bacterial infection by using systemic ozone. Bocci also proposed the rationale of this indication. Fortunately, we have several clinical studies about the efficacy of ozone in viral infections: herpes, hepatitis B, hepatitis C and HIV.
Ozone administration ways.
Ozone for systemic diseases should be used in a systemic way :
A. Indirect Endovenous Administration (IEV). As ozone is a gas cannot be directly injected into the blood mainstream, to avoid gas embolism. Special medical devices have been manufactured and EU certificated by different manufacturers to allow ozone dissolve into the patients’ blood risk free. For details on this technique, please read World Federation of Ozone Therapy – WFOT’s book . Based on the information from the three Chinese Hospitals that are presently performing and official clinical trial and also on the protocol presented and pre-accepted in Universitá della Sapienza in Rome, the proposed treatment will be:
– 100 mL of blood and 100 mL of ozone gas at 30 mcgr/mL concentration.
– In-hospital patients: each 12 hours application for minimum 14 days.
B. Rectal Inssuflation (RI). Rectal inssuflation is not so exact as IEV but it can be the only option for patients where peripheral veins don’t allow the previous technique. For details on this technique, please read World Federation of Ozone Therapy – WFOT’s book
We propose the following protocol:
– Day 1: 100 mL at 30 mcgr/mL concentration.
– Day 2: 150 mL at 30 mcgr/mL concentration.
– Day 3 – 14: 200 mL at 30 mcgr/mL concentration.
– In-hospital patients: each 12 hours application for minimum 14 days.
Complementary treatments to ozone administration.
To help ozone effect, it is advisable although not mandatory, the administration during the ozone treatment of:
– Vitamine C: 3 gr each 12 hours, 6 hours after ozone administration. 1 gr each 12 hours is standardize in Italy and Spain protocols for COVID19.
– Glutatione: 600mg each 12 hours, 6 hours after ozone administration. This substance is administered because ozone effect is partially based on it and old patients may have a low blood glutatione level.
1. Enhance respiratory function
2. Stop the blood interleukine storm
3. Limit patients needing ICU
4 Shorten the time in hospital.
1. Confirmed patients (or legal guardian) sign a written informed consent form.
2. Aged from 18 to 80 years, male or female.
3. Patients with positive detection of 2019 Novel Coronavirus Pneumonia fluorescence RT-PCR in respiratory specimens or blood samples.
4. Mild ill and severe ill patients NOT IN ICU are grouped based on the “Handbook of COVID-19 “Prevention and Treatment”
1. Patients who may be transferred to other hospitals that are not included in the trial within 72 hours.
2. G-6PD defect (Major Favism).
3. Pregnancy, especially early pregnancy.
4. Patients who continually use immunosuppressant, or are organ transplant recipients within 6 months.
5. Patients who are receiving other clinical trials.
WE SHOULD RANDOMIZE the patients going for control IEV or RI groups:
1. Control group. 60 patients. Conventional treatment.
2. Mild ill patients: 15 patients. Conventional treatment + ozone protocol A (IEV).
3. Mild ill patients: 15 patients. Conventional treatment + ozone protocol B (RI).
4. Severe/critical patients: 15 patients. Conventional treatment + ozone protocol A.
5. Severe/critical patients: 15 patients. Conventional treatment + ozone protocol B.
1. Chest CT or XRay: interstitial pattern.
2. Whole blood cell analysis: leucocytes recount.
3. Oxygenation index: SpO2.
4. Inflammation index: PCR. (optional: IL6, procalcitonin, ferritin, D-dimer)
5. Fever: axillary temperature.
6. Recovery rate.
7. Conversion rate of severe patients.
8. Mortality rate.
1 Zhou W. The coronavirus handbook. New York: Skyhorse Publishing; 2020. ISBN: 9781510762411.
2 WHO. Clinical management of severe acute respiratory infection when Novel coronavirus (2019-nCoV) infection is suspected: Interim Guidance. WHO/nCoV/Clinical/2020.2.
3 Bocci V. Ozone: A new medical drug. Netherlands: Springer; 2011.
4 Baeza J, Cabo JR, Gómez M, et al. WFOTs Review on Evidence Based Ozone Therapy. World Federation of Ozone Therapy. 2015:1–116.
5 Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015;3:4.
6 Pecorelli A, Bocci V, Acquaviva A, et al. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells. Toxicol Appl Pharmacol. Feb 15 2013;267(1):30-40.
7 Re L, Martinez-Sanchez G, Bordicchia M, et al. Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result. Eur J Pharmacol. Nov 5 2014;742:158-162.
8 Hernández-Rosales FA, Calunga-Fernández JL, Turrent-Figueras J, Menéndez-Cepero S, MontenegroPerdomo A. Ozone therapy effects on biomarkers and lung function in asthma. Arch Med Res. 2005 SepOct;36(5):549-54.DOI:10.1016/j.arcmed.2005.04.021
9 Borrelli E, Bocci V. Oxygen Ozone Therapy in the Treatment of Chronic Obstructive Pulmonary Disease: An Integrative Approach. Am J Clin Exp Med. 2014;2(2):9-13. DOI:10.11648/j.ajcem.20140202.11
10 Vinnik IS, Salmina AB, Tepliakova OV, Drobushevskaia AI, Pozhilenkova EA, Morgun AV, Shapran MV, Kovalenko AO. [The results of combined ozone therapy using in complex treatment of soft tissues infections in patients with diabetes mellitus type II]. Khirurgiia (Mosk). 2015 63-69. DOI:10.17116/hirurgia2015263-69. PMID: 26031822.
11 Delgado-Roche L, Riera-Romo M, Mesta F, Hernández-Matos Y, Barrios JM, Martínez-Sánchez G, AlDalaien SM. .Medical ozone promotes Nrf2 phosphorylation reducing oxidative stress and pro-inflammatory cytokines in multiple sclerosis patients. Eur J Pharmacol. 2017 Sep 15;811:148-154. DOI: 10.1016/j.ejphar.2017.06.017.
12 Tong N, Chaoliang Lv, Guangkun Yi, Huamin Tang, Cunji Gong, Shizhen N. Therapeutic Effect of Medical Ozone on Lumbar Disc Herniation. Med Sci Monit 2018; 24:1962-1969 DOI:10.12659/MSM.903243
13 Bocci V. Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis. Med Hypotheses. 1992 Sep;39(1):30-4. PMID:1435389
14 Bocci V. Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses. 1996 Feb;46(2):150-4. PMID: 8692040
15 Bassi P, Sbrascini S, Mattassi R, D’Angelo F, Franchina A. [Ozone in the treatment of herpes zoster]. Riv Neurobiol. 1982 Jul-Dec;28(3-4):328-33.
16 Gierek-Lapińska A, Antoszewski Z, Myga B, Skowron J. [Preliminary report on using therapeutic ozone in infectious conjunctivitis and keratitis and in corneal degeneration]. Klin Oczna. 1992 May-Jun;94(5-6):137-8. PMID: 1453672
17 Mandzhgaladze NR, Kharebava ER, Didia TsG, Ardzhevanishvili MD, Gudzhabidze MV, Chigiashvili TsN. [Influence of intravenous ozone treatment on the level of different specificity antibodies]. Georgian Med News. 2006 Sep;(138):93-5.
18 Huang J, Xiang Y, Gao L, Pan Y, Lu J. Topical ozone therapy: An innovative solution to patients with herpes zoster. J Cent South Univ (Med Sci). 2018;43(2): 168-172. DOI:10.11817/j.issn.16727347.2018.02.011
19 Jiao XJ, Peng X. [Clinilal study of medical ozone therapy in chronic hepatitis B of 20 patients]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008 Dec;22(6):484-5. PMID: 19544653
20 Chernyshev AL, Filimonov RM, Karasev AV, Neronov VA, Maksimov VA. [Combined treatment including ozonotherapy of patients with viral hepatitis ]. Vopr Kurortol Fizioter Lech Fiz Kult. 2008 May-Jun;(3):19-22. PMID:18655281
21 Neronov VA. Experience with the use of ozone for the treatment of chronic viral hepatitis. Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):14-7.
22 Cespedes-Suarez J, Martin-Serrano Y, Carballosa-Peña MR, Dager-Carballosa DR . Response of patients with chronic Hepatitis B in one year of treatment with Major Autohemotherapy. J Ozone Ther. 2018:2(3) DOI:10.7203/jo3t.2.3.2018.11459
23 Zaky S, Kamel SE, Hassan MS, Sallam NA, Shahata MA, Helal SR, Mahmoud H. Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C. J Altern Complement Med. 2011 Mar;17(3):259-63. DOI:10.1089/acm.2010.0016. PMID:21417811
24 Cespedes-Suarez J, Martin-Serrano Y, Carballosa-Peña MR, Dager-Carballosa DR. The immune response behavior in HIV-AIDS patients treated with Ozone therapy for two years. J Ozone Ther. 2019:2(3). DOI:10.7203/jo3t.2.3.2018.11458
25 Guangjian N, Hongzhi Y. Clinical study for ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19). ChiCTR2000030165. Academy of Medical Engineering and Translational Medicine, Tianjin University. 2020-02-24. http://www.chictr.org.cn/showprojen.aspx?proj=49947
26 Linlin H, Xiangdong C. A randomized controlled trial for the efficacy of ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19). ChiCTR2000030006. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. 2020-02-19. http://www.chictr.org.cn/showproj.aspx?proj=49737
27 Huiling H, Tong X. A multicenter randomized controlled trial for ozone autohemotherapy in the treatment of novel coronavirus pneumonia (COVID-19). ChiCTR2000030102. Tianjin Huanhu Hospita. 2020-02-23.http://www.chictr.org.cn/showproj.aspx?proj=49747
28 Liang T. Handbook of COVID-19 Prevention and Treatment. Zeijang: FAHZU; 2020.
puteti descarca materialul : OTCoV22F