Ozone Therapy in COVID-19

Maria Emilia Gadelha Serra, MD, MSc.

President
Sociedade Brasileira de Ozonioterapia Médica (SOBOM)
Alpha Group Medicina Integrativa
São Paulo - Brazil
• Physician graduated from CUM LAUDE by the Federal University of Rio de Janeiro (UFRJ), Brazil, in 1988
• Medical residence trainning program in Otorhinolaringology at University of São Paulo (USP), Ribeirão Preto, São Paulo State, Brazil,
concluded in 1991
• Medical Scholarship from Ministry of Education, Culture, Sports, Science and Technology of Japan (MONBUSHO), Universities of
Kyushu and Kurume, Japan, in 1991 and 1992
• Master's degree from the Federal University of São Paulo (UNIFESP), Brazil, in 2004
• Certificate of Hyperbaric Oxygen Therapy from Brazilian Society of Hyperbaric Medicine (SBMH), São Paulo, Brazil, in 2010
• Postgraduate in Medical Expertise from Santa Casa de São Paulo, Brazil, in 2020
• Founder and 1st President-Director of the Brazilian Association of Ozone Therapy (ABOZ) in 2006 and 2014
• Founder and current President of the Brazilian Society of Medical Ozone Therapy (SOBOM) since 2019
• Member of the Natural Products Committee of the Brazilian Academic Consortium for Integrative Health (CABSin) since 2020
• Training in German and Swiss Biological Medicine in Germany, Switzerland and Colombia - Biological Medicine and Homotoxicology
Specialist - Certificates issued by Hufeland Gasellschaft für Gesamtmedizin eV (Germany), the International Society of
Homotoxicology eV (Germany) and Dr. O'Byrne Biological Medicine Center, Colombia, completed in 2004 and Paracelsus Klinik
Lustmühle, Switzerland, in 2016
• Coordinator of the Course of Integrative Medicine at the Foundation for Support to Research and Study in the Health Area (FAPES) in
São Paulo, Brazil, since 2019
• Researcher in the area of ​Medical Ozone Therapy with ongoing research projects registered at Plataforma Brasil since 2019
1. Introduction to Ozone Therapy – Biological Mechanisms and Scientific
Evidences – Evidence Gap Map of Medical Ozone Therapy

2. Ozone Therapy in COVID-19 – Foundation and the Brazilian Research

3. Ozone Therapy in Post-COVID Syndrome

4. Ozone Therapy in COVID-19 Vaccines Adverse Events

5. Conclusions
1. Introduction to Ozone Therapy
Biological Mechanisms
Scientific Evidences
Evidence Gap Map

3
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688103/
“Oxygen is one of the most widely used therapeutic agents.
It is a drug in the true sense of the word, with specific
biochemical and physiologic actions,
a distinct range of effective doses,
and well-defined adverse effects at high doses.”
 Ozone
Oxygen “Activated Oxygen”
https://www.youtube.com/watch?v=va-xZgqVG0A
 Ozone is produced in
the human body in
the process of
activating antibodies.

Science 298, Dez. 2002

Biomolecule
Ozone Therapy
Medical Societies of Ozone Therapy
It goes
into It leaves ALWAYS
Medicinal Medicinal an
Oxygen Ozone Oxygen-
Ozone
Mixture
@draemilia serra
 ALWAYS
an
Oxygen-Ozone
Mixture
 0,05 % O 3 5 % O3
99,95 % O2 95 % O2

1 mcg /ml O3 100 mcg/ml O3

Medicinal
Ozone
@draemilia serra
 Infections

Vascular
Imunno &
Diseases Inflammatory
Modulation

Ozone Therapy
2,3-DPG plays an important role in the functionality of
red blood cells, as the affinity of hemoglobin for oxygen
depends on 2,3-DPG.

2,3-DPG releases 4 oxygen molecules.

Ozone Therapy Improves Oxygenation

10 minutes
Pre-Ozone Post-Ozone
Induction of Nitric Oxide Synthetase
Increased Nitric Oxide
Vasodilation
Induction of Nitric Oxide Synthetase
Increased Nitric Oxide
Vasodilation
https://www.researchgate.net/publication/328116777_Antioxidant_and_Oxidative_Stress_A_Mutual_Interplay_in_Age-Related_Diseases
 Ozone therapy
- within the therapeutic window –
induces mild, controlled and
transient oxidative stress.
https://www.essentialnutrition.com.br/media/artigos/vitalift/3.pdf
https://pubmed.ncbi.nlm.nih.gov/25699252/
Ozone therapy induces Nrf2 release by Keap 1
https://www.pagepressjournals.org/index.php/ozone/article/view/9014
42µg/ml (Bocci 1998)

https://pubmed.ncbi.nlm.nih.gov/10766603/
Ozone Therapy and IL-6

Bocci V et al. Toxicol, 2005;19:55-61

Ozone Therapy and TNF-α

Bocci V et al. Toxicol, 2005;19:55-61

Oze Therapy and TNF-α

Menendez S et al. Mediators Inflamm 2005; 2005(1):16-22

Multilevel Action of Ozone Therapy
 Multiple Myeloma
After Bone Marrow
Transplantation and
Ozone Therapy
(Systemic +
Local Injections)

December 2016 September 2017

So…Ozone therapy
is NOT a panacea.
The Ozone Therapy protocols used in COVID-19 include varied
combinations of:

Major AutoHemotherapy (MAH)

Minor AutoHemotherapy

Rectal insufflation
Visual appearance of a plastic transfusion bag of:

A - Venous blood collected to perform the MAH procedure

B- Venous blood exposed to the oxygen-ozone mixture applied

during the Major Auto-Hemotherapy (MAH) procedure.
 Ozone Therapy Safety
▪ In the 1980s, Medicinal Ozone Oxygen Therapy
was evaluated from a safety point of view: a
German study evaluated data on almost 5.6
million treatments with this therapy and found
the incredible figure of only 40 cases with mild
side effects and only 6 deaths. This means that
Medicinal Ozone Therapy has a 0.0007% risk of
complications and a 0.0001% risk of death.
▪ There are only 7 (seven) cases of death related
to Ozone Therapy described in all medical
literature in 130 years of this medical procedure
history.
▪ It is, therefore, an extremely safe medical
therapy.

Jacobs, MT, Investigation into pitfalls and typical complications in ozone-oxygen therapy,
OzoNachrichten 1982; 1:5.
http://mtci.bvsalud.org/pt/mapas-de-evidencia-2/
This map presents an overview of the evidence and gaps that exist on
the effects of medical Ozone Therapy for various clinical and health
conditions of people. Based on a broad bibliographic search of
published and unpublished studies between 2000 and mid-2019, 14
systematic reviews were included in the Map. The medical Ozone
Therapy evidence map was carried out by BIREME/PAHO/WHO in
collaboration with the Brazilian Society of Medical Ozone Therapy
(SOBOM) and institutional support from the World Federation of
Ozone Therapy (WFOT).

https://mtci.bvsalud.org/pt/efetividade-clinica-da-ozonioterapia-medica/
https://mtci.bvsalud.org/pt/efetividade-clinica-da-ozonioterapia-medica/
https://mtci.bvsalud.org/pt/efetividade-clinica-da-ozonioterapia-medica/
http://mtci.bvsalud.org/mapas-de-evidencia/mapa-de-evidencia-ozonioterapia-medica/
http://mtci.bvsalud.org/mapas-de-evidencia/mapa-de-evidencia-ozonioterapia-medica/
Main findings
• Most primary studies included in systematic reviews are concentrated in countries in Europe (26 studies) and Asia (18 studies). Other studies are from the
United States (1), Brazil (4) and Cuba (5).

• All reviews included are systematic and effective, with the majority being randomized clinical trials (8). Another 4 reviews are from observational clinical
studies, and another 2 reviews are from non-randomized clinical trials.

• To assess the reliability level of the reviews, the AMSTAR tool (Measurement Tool to Assess Systematic Reviews) was applied, resulting in 9 high level
reviews, 3 moderate level reviews and 2 low level reviews.

• Most available evidence focuses on applied Ozone Therapy for pain reduction. Other evidence assesses the effect of Ozone Therapy for
healing, reducing inflammation and reducing infection.
• As for the type of intervention, there is a concentration of evidence in the parenteral application of the oxygen-ozone gas mixture, followed by local and
topical application.

• In addition to the expected clinical outcomes, the map includes a group of outcomes related to possible adverse effects of Ozone Therapy and indicates a
concentration of evidence for site infection.
2. Ozone Therapy in COVID-19
Foundation and the Brazilian Research
https://doi.org/10.1080/21645515.2021.1945904
 The mechanisms of action of Ozone Therapy,
proposed by the Brazilian Society of Medical
Ozone Therapy (SOBOM), applicable to the main
complications of COVID-19 are based on:

1. General improvement in oxygen metabolism,

increasing oxygenation and gas exchange in the
lungs and peripheral tissues
2. Restoring the balance of the cellular redox
state
3. Increased synthesis of intracellular antioxidant
enzymes
4. Promotion of IFN-gamma induction (main
endogenous humoral mechanism of antiviral
control)
5. Reduction of pro-inflammatory cytokines
6. Increasing the effectiveness of antigen-
antibody dynamics
7. Antiviral action
8. Vasodilation and increased tissue perfusion
9. Modification and attenuation of the structural
conformation of virions, favoring the antiviral
immune response (“autovaccine”)
10. Hemorrheological improvement, reducing red
blood cell aggregation, decreasing blood viscosity
and optimizing blood flow
11. Favoring the regeneration of injured tissues,
due to the release of growth factors
Ozone Therapy – all stages of COVID-19 12. Obtaining a sense of well-being, as reported
by most patients, through activation of the
@draemilia serra https://www.jhltonline.org/article/S1053-2498(20)31473-X/fulltext neuroendocrine system.
 Clinical, Open, Phase III, Multicenter, Prospective, Comparative, Controlled,
Randomized Study to Assess the Effectiveness of Systemic Oxygen Therapy
with Medicinal Ozone (Ozone Therapy) in Early Control of Disease Progression
in Patients with COVID-19 Acute Infectious Respiratory Symptoms
Protocol SOBOM Brazilian Society of Medical Ozone Therapy (SOBOM)
Code 5704 Department of Clinical Research
CAEE 30838820.2.1001.5704 secretariasobom@gmail.com

Principal Coordinator and Researcher Assistant Coordinator Researcher

Dra. Maria Emilia Gadelha Serra Dr. Gustavo Vilela de Paula e Silva
Doctor - CREMESP 63451 Doctor - CREMESP 91619
CEO of SOBOM
May 2020
Ozone Therapy in COVID-19
 Systemic Ozone Therapy
in COVID-19

ALPHA SOBOM OMEGA SOBOM

Protocol Protocol CONTROL-GROUP
Minor Autohemotherapy +
Major Autohemotherapy
Rectal Ozone Insufflation

SOBOM Protocol
Code 5704
www.sobom.com.br
▪ They will receive standard treatment for COVID-19, according to the
individual needs determined by doctors and / or hospital.
▪ In addition, the Major Autohemotherapy (MAH) will be added.
ALPHA
▪ This therapy consists of collecting a quantity of blood through some arm
vein. This volume of blood is proportional to Participant´s weight, and
SOBOM
varies, on average, between 80 to 200mL. Blood is stored in a plastic
transfusion bag, just as it is in a blood donation. The gaseous mixture
containing oxygen and ozone is then injected into the bag, waiting for
Protocol
about 2-3 minutes for the gases to mix with the blood, then it is Major Autohemotherapy
transfused back into the body through the same vein used for collection.
(MAH)
Therefore, there is no blood loss in this procedure.
▪ This treatment is done in an extremely clean way - using disposable and
sterilized materials - and lasts an average of 30 minutes.
▪ This procedure is performed repeatedly, according to the protocol
established for the different groups. Between 7 and 14 sessions of this
treatment will be applied if the Participant is drawn for the groups of the
ALPHA SOBOM Protocol, according to the needs and with the group that
has been drawn.
SOBOM Protocol
Code 5704
 OMEGA ▪ They will receive standard treatment for COVID-19, according to
with their individual needs determined by doctors and/or hospital.

SOBOM ▪ In addition, two procedures will be added in which the gas mixture of
oxygen and ozone is applied by different routes: Minor Autohemotherapy
(MiAH) and Rectal Insufflation (RI).

Protocol ▪ In Minor Autohemotherapy, a 5mL syringe of blood is collected from some

arm vein. The blood is then mixed with 5mL of the gas mixture containing
Minor AutohemoTherapy oxygen and ozone previously placed inside the syringe and then injected
(MiAH) intramuscularly into the buttock. 7 applications of MiAH will be performed
+ Rectal Insufflation (RI) in this study.
SOBOM Protocol ▪ In the case of Rectal Insufflation, the Participant is placed lying on his/her
Code 5704 left side so that a sterile thin plastic tube, known as a rectal tube, is
introduced in the final part of his intestine (similar to the placement of a
suppository) and then it will be a volume between 250 to 500mL of the
mixture of oxygen and ozone gases is applied inside the intestine. The gas
mixture will remain inside the intestine until it is absorbed by the body or
eliminated in the form of flatus (gases). Between 14 and 28 Rectal
Insufflation sessions will be held in the OMEGA SOBOM Protocol groups,
according to needs and with the group for which the Participant has been
drawn.
https://link.springer.com/article/10.1007/s42399-020-00374-1
 Major Autohemotherapy
2 mL / Kg of blood
2 mL / Kg of Medicinal Ozone
concentration = 45 mcg / mL
1x / day for 14 days
Total = 14 sessions
ALPHA SOBOM Protocol
Major Autohemotherapy
Major Autohemotherapy
2 mL / kg of blood
2 mL / Kg of Medicinal Ozone
concentration = 45 mcg / mL
1x / day every other day
Total = 7 sessions
OMEGA SOBOM Protocol
Minor Autohemotherapy +
Rectal Insufflation
Control-Group Ozone Therapy Free
GROUP 1 (CRITICAL)
GROUP 2 (SERIOUS)
GROUP 3 (ALERT)
Minor Autohemotherapy
5 mL of blood GROUP 1 (CRITICAL)
GROUP 4 5 mL of Medicinal Ozone
(OUTPATIENT) concentration = 40 mcg / mL GROUP 2 (SERIOUS)
1x / day every other day
Total = 7 sessions GROUP 3 (ALERT)
+
Rectal Insufflation 2x daily
Total = 28 sessions
Minor Autohemotherapy
5 mL of blood
5 mL of Medicinal Ozone
concentration = 40 mcg / mL
GROUP 4
1x / day every other day
(OUTPATIENT)
Total = 7 sessions
+
Rectal Insufflation 1x daily
Total = 14 sessions
SOBOM Protocol
Code 5704
SOBOM Protocol ELIGIBLE PARTICIPANT
Code 5704

Free and Informed Consent Form

Exclusion Criteria
Classification of the Participant ❑ G6PD enzyme deficiency (activity below
in the Specific Group Study 60% according to Yoshida classification)
❑ Pregnancy
Inclusion criteria GROUP 1 (CRITICAL)
❑ Lactating women
• Data collect
❑ Patients with acute infectious respiratory
• Laboratory Exams
GROUP 2 (SERIOUS) ❑ Clinically decompensated
symptoms evaluated in hospital, using as GROUP 3 (ALERT) hyperthyroidism
• Imaging Exams
a basis the flowchart suggested by ❑ Severe decompensated arterial
Hospital Israelita Albert Einstein • (1-7-14-21-60 days) GROUP 4 (OUTPATIENT) hypertension
(19.03.2020) According SOBOM ❑ Active or recent bleeding (bleeding) from
❑ Laboratory diagnosis confirmed for Protocol Code 5704 organs
COVID-19 (RT-PCR or serology) ❑ Severe anemia (Hemoglobin <6 g / dL)
❑ Both sexes ❑ Unstable period of severe cardiovascular
❑ Age equal to or above 18 years-old INTERVENTION PHASE FOR 14 DAYS disease
❑ Signed Free and Informed Consent Form ❑ Participation in another clinical study for
❑ Availability to follow the treatment less than 30 days
protocol OMEGA SOBOM Protocol ❑ Impossibility of adhering to the research
ALPHA SOBOM Protocol protocol
Minor Autohemotherapy + ❑ Any important clinical condition that, in
Major Autohemotherapy Rectal Insufflation the Investigator's opinion, may bring risks
Groups 1, 2 and 3: 14 sessions to the patient and prevent him from
Groups 1, 2 and 3: 7 + 28 sessions
Group 4: 7 sessions proceeding safely.
Group 4: 7 + 14 sessions

Withdrawal Withdrawal
(any time) OUTCOMES (any time)
 Flowchart Participants > 18 years
Suspect for COVID-19
Group 1 - CRITICAL
SpO2 <93%
Mechanical ventilation
AND / OR Presence of shock
(Systolic BP <90 mmHg
or Diastolic BP <40 mmHg or
MAP <65 mmHg)
AND / OR organs failure
Group 1
CRITICAL
Need of Immediate
Hospitalization
Group 2
SERIOUS
Group 2 - SERIOUS
SpO2 <93%
Respiratory Rate > 30 PMRI
Non-invasive ventilation
Increase in lung injuries
> 50% in 24-48h
Absence of shock
Absence of organs failure
* Organs failure
Thrombocytopenia AND / OR Acute kidney failure
AND / OR Change in the level of consciousness
Group 4 - OUTPATIENT
Acute infectious symptoms: fever,
*
Patients discharged for home isolation
SpO2 ≥ 93%
sore throat, runny nose, cough, Respiratory Rate <24 PMRI
Grupo 1 myalgia, prostration, AND / OR
anosmia, loss of taste, dyspnoea, Absence of dyspnea +
CRÍTICO
Study Groups diarrhea Alteration of pulmonary auscultation
Group 4
Group 3 - ALERT
OUTPATIENT (Evaluation for 12 hours)
Persistence or increase in
fever after 3 days AND / OR
Hospital discharge with SpO2 ≥ 93%, RR ≥ 24 PMRI
orientation and <30 PMRI AND / OR
Hospital internment RT-PCR for Sars-Cov-2 Dyspnea + Alteration of
Chest CT Group 3 Home isolation (14 days)
pulmonary auscultation AND
RT-PCR for Sars-Cov-2 ALERT Oseltamivir (risk groups with / OR Cyanosis AND / OR Age>
Lab Exams influenza syndrome) 60 years AND / OR
Oxygen Therapy Consider antibiotics Comorbidities (SAH , DM,
cardio-cerebrovascular
disease, immunosuppression,
Clinical deterioration OR neoplasms, previous lung
Hospital internment Organs failure disease) AND / OR Perception
In case of suspected
of severity by the physician in
definition (ICU or other)
* pneumonia (Chest CT),
introduce antibiotic
- Absence of shock
AND
- Absence of organs failure
RT-PCR for Sars-Cov-2
Hospital internment
Hospital internment CHEST CT
Lab Exams
SOBOM Protocol
+ others
Code 5704
Clinical improvement + Chest CT
≤ 50% llung injuries
* Adapted from the Flowchart suggested by Hospital Israelita Albert Einstein (19.03.2020)
Extended List of Complementary Exams
Pre-, During and Post-Study
(1-7-14-21-60 days) - according to SOBOM Protocol - CEP 5704
Blood: • Uric acid
• Complete blood count
• Serum dosage of the enzyme G6PD (Glucose 6-
Phosphate-Dehydrogenase)
• Blood sedimentation rate (ESR)
• TSH
• TP and TTPA
• Free T4
• CD4 / CD8 ratio
• Free T3
• D dimers
• CPK
• Ultra-sensitive Reactive Protein C
• Sodium
• Anti-Nuclear Factor (FAN)
• Potassium
• Ferritin
• Chlorine
• Transferrin saturation index
• Phosphor
• TGO / AST
• IL-6
• TGP / ALT
• IL-10
• GT-Gamma
• TNF-alpha
• DHL
• Procalcitonin
• Alkaline phosphatase
• 25 (OH) vitamin D
• Total bilirubins and fractions
• MTHFR mutation search
• Triglycerides
• Leiden Factor V
• Fasting blood glucose Urine: Urinary MDA, urine I and uroculture
• ABO blood type
• Fasting insulin Imaging exam: Chest computed tomography
• B-hCG for women of childbearing age
• Glycated hemoglobin
• Arterial blood gas analysis
• Urea SOBOM Protocol
• Troponin
• Creatinine
• Cerebral Natriuretic Peptide (BNP) Code 5704
 Ozone Therapy
Discomfort, Complications and Risks
Related to blood collection:
• risk of pain, infection, bleeding and bruising at the site of the needle stick in the vein
• short-term fainting associated with stinging needle pain in the vein (known as a “vagal reflex”)

▪ Adverse events of minor severity eventually presented can be

easily resolved with general clinical measures (use of pain
medication, use of antibiotics in cases of infection, use of
hydration serum through the vein in case of pressure drop or
“vagal reflex”, use of serum with glucose through the vein in case
of hypoglycemia).

▪ Medicinal Ozone Oxygen Therapy may cause an increase or

decrease in the effects of other medications being used. If this
happens, it may be necessary to adjust the dose or even modify
the medical prescription, and this change must always be
performed by a medical doctor. SOBOM Protocol
Code 5704
 Ozone Therapy
Discomfort, Complications and Risks
Related to Major Autohemotherapy and Minor Autohemotherapy: they are extremely rare and can be avoided by
respecting standard antisepsis techniques, performing local compression after removal of the venipuncture, and avoiding
performing the procedure on an individual who has fasted for more than 3 hours or dehydrated, so it is recommended that
the Participant had eaten and taken plenty of water.
Are they:
▪ risk of pain, infection, bleeding and bruising at the site of the needle stick in the vein
▪ pressure drop (hypotension)
▪ palpitations (tachycardia)
▪ transient drop in blood sugar (hypoglycemia)
▪ headache
▪ insomnia
▪ itchy skin
▪ gastritis (stomach pain)
▪ nausea
▪ fleeting sensation of heat and redness of the body
▪ tingling in the lips and fingertips
SOBOM Protocol
▪ short-term fainting associated with stimulation of the needle prick pain in the vein
Code 5704
(known as a “vagal reflex”)
 Ozone Therapy
Discomfort, Complications and Risks

Related to Rectal Insufflation:

▪ nausea
▪ belly bulging
▪ belly pain (intestinal colic)
▪ tingling in lips and fingertips
▪ transient decrease in blood sugar (hypoglycemia)
▪ intestinal stimulation (desire to eliminate feces a few moments after application)

SOBOM Protocol
Code 5704
This evidence map presents a graphical summary of clinical studies on the application of Ozone Therapy in cases of
COVID-19.

From a wide bibliographic search, 11 clinical studies were included in the map and categorized by type of intervention
and outcomes.

The studies evaluated the effect of 4 types of intervention with Ozone Therapy: Major Autohemotherapy, Minor
Autohemotherapy, Rectal Insufflation and Ozonized Saline; for 29 outcomes related to COVID-19, which on the map are
divided into 6 groups: 1- clinical improvement; 2-hospitalization; 3- inflammatory, thromboembolic, infectious or
metabolic markers; 4- radiological aspects, 5- viral infection and 6- adverse events.

Circles located at the intersections between interventions and outcomes represent the identified studies and quantity.
The color of the circle represents the study design: Green for Randomized Clinical Trials (RCTs), Yellow for Non-
Randomized Clinical Trials (Non RCTs) and Quasi-experimental Clinical Studies, and Red for Case Reports and Case Studies
and Control.

The outcomes present in 6 or more studies were considered important. Other elements of characterization of the
studies, such as population and country of origin of the study, are represented in the filters.
https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
Main Findings

• The studies took place in 2020 in the following countries: Spain (5 articles), China (2 studies), Italy (2 studies),
India (1 study) and Iraq (1 study).
• The 11 clinical studies analyzed involved a total of 259 patients with COVID-19 who received Ozone Therapy, all
results were positive, both in patients with mild to severe severity, being mild to moderate in 2 studies, moderate to
severe in 1 study, mild to severe in 1 study, moderate in 1 study, severe in 6 studies.
• The most reported type of intervention was Major Autohemotherapy, present in 19 outcomes, followed by
Rectal Insufflation, present in 17 outcomes.
• The reported outcomes were: general improvement in clinical symptoms of COVID-19 (11 studies), reduction in
hospital stay (6 studies), decrease in C-reactive protein (9 studies), decrease in ferritin (6 studies), decrease in lactate
dehydrogenase (7 studies), decreased D-dimer (7 studies), absence of reported adverse events (9 studies).

• The concentration of medicinal ozone in the Major Autohemotherapy ranged from 20 to 45mcg/mL, with
40mcg/mL being the most used concentration. For the Rectal Insufflation route, a concentration of 35-40mcg/mL was
used, with the concentration of 35mcg/mL being the most used.

https://public.tableau.com/profile/bireme#!/vizhome/ozonioterapia-covid-pt/evidence-map
Preliminary Results

The Major Autohemotherapy (MAH)

SINCE THE FIRST SESSION reduces
shortness of breath, decreases the
need for oxygen (WHO scores),
prevents progression to disease
severity, reduces some of the main
markers of inflammation and D-dimer,
which indicates that it is protecting
from thrombotic and vascular
complications, perhaps from post-
COVID syndrome as well, and mainly
improves general health (WHO scores).

Rectal insufflation + Minor

Autohemotherapy (MiAH)
demonstrated liver protection, with a
reduction in altered enzymes.
 Houston,
we have
a problem...
3. Ozone Therapy in Post-COVID Syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340747/
 Post-COVID Syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340747/
https://www.nature.com/articles/s41591-021-01283-z
https://www.sciencedirect.com/science/article/pii/S0163445321000098
 https://pubmed.ncbi.nlm.nih.gov/32945158/
https://www.frontiersin.org/articles/10.3389/fimmu.2012.00143/full
Post-COVID Syndrome
Viral cell injury
Multiple organs Microvascular ischemia

Innate Immune Response Immobility

Cytokines
Hyperinflammation Metabolic changes

Increased risk of infections

Procoagulant state
 Vitamin D Gut Flora
Mast Cells VDR (Vitamin D Receptor)
&
Histamine
RANTES
Nutritional
Deficiencies
MTHFR Nrf2
Mitochondrial Polimorfisms TNF-Alpha
Disfunction Oxidative Stress
• This review comprises a total of 74 original
peer-reviewed articles. It focuses primarily on
ozone as a modulator of the NF-κB / Nrf2
pathways and the expression of IL-6 / IL-1β.

• These molecular mechanisms support the

cytoprotective effects of Ozone
Therapy against tissue damage
present in many inflammatory
diseases, including viral infections.

• Conclusions: The potential cytoprotective role

of Ozone Therapy in the management of organ
damage induced by COVID-19 deserves further
investigation. Controlled clinical trials are
needed.

https://www.mdpi.com/2076-3921/9/5/389
https://ijmpronline.com/current-issues
https://ijmpronline.com/current-issues
https://www.mdpi.com/1999-4915/13/3/378/htm
https://www.mdpi.com/1999-4915/13/3/378/htm
https://www.mdpi.com/1999-4915/13/3/378/htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135115/
Immediate Treatment Ozone Therapy

Health
4. Ozone Therapy in COVID-19 Vaccines Adverse Events
https://www.bayer.com/en/news-stories/covid-19-vaccines
https://www.ahajournals.org/doi/epub/10.1161/CIRCRESAHA.121.318902
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-july-13-2021
 Polysorbate
and Anaphylaxis

https://www.ncbi.nlm.nih.gov/pubmed/29481891
Histamine-Releasing Properties of Polysorbate 80

https://www.ncbi.nlm.nih.gov/pubmed/2416204
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myocarditis.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162819/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422981/
https://pubmed.ncbi.nlm.nih.gov/28097518/
https://onlinelibrary.wiley.com/doi/abs/10.1002/cbf.2930
https://www.pagepressjournals.org/index.php/ozone/article/view/7512/0
https://pubmed.ncbi.nlm.nih.gov/34115170/
https://onlinelibrary.wiley.com/doi/10.1002/cbin.11589?af=R#
Ozone Therapy and Muscle Oxygenation

https://www.ncbi.nlm.nih.gov/pubmed/12804078
Ozone Therapy
in Fibromyalgia

https://dialnet.unirioja.es/descarga/articulo/4828950.pdf
 Ozone Therapy
and Recovery
of Sequelae of
Stroke (Stroke)
Motor Function
of the Upper Limb

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146136/
 Ozone Therapy
and
Complex Regional
Pain Syndrome
(CRPS)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502773/pdf/11916_2019_Article_776.pdf
5. Conclusions
Tissular hypoxia reduction Chronic inflammation modulation

Nitric Oxide synthesis Immune system modulation

COVID-19 vacines Oxidative stress

adverse events management reduction
Wellbeing
Gut flora Infections’s control
reequilibrium assistance (bacteria
and virus)
Fatigue reduction
Dental foci treatment Healing improved Metabolic control
PS nervous system activation (glucose)
D 021-0002 11.11.2004