Table 1.
Summary of main clinical studies of ozone therapy in COVID-19 patients.
| References | Study type | Patients enrolled | Ozone concentration and protocol | Results | Disease stage |
|---|---|---|---|---|---|
| Franzini et al., 2020 | Case study | Fifty hospitalized patients. All underwent SOC+ AHT | AHT 200 ml 45 μg/ml O2-O3 4 cycles of mixture of O2-O3 once a day for 5 consecutive days | A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer), amelioration in the major respiratory indexes (respiratory and gas exchange markers: SpO2%, PaO2/FiO2 ratio). | Patients in ICU |
| Araimo et al., 2021 | Case control study | Fourteen (O2-O3 + SOC) VS 14 (control group: only SOC) | AHT 30 μg/ml O2-O3 twice/day for 7 consecutive days | Reduction after treatment of IL-6, CRP, D dimer | All patients had ventilatory support or venturi mask |
| Fernández-Cuadros et al., 2021 | Case control study | Fourteen (rectal ozone + SOC) VS 14 (SOC) | Rectal ozone (150 ml) concentration 35 μg/ml; for eight sessions (one session/day) | Improved O2 saturation and decreased O2 supply. Lymphocyte count improved (p < 0.05). Biomarkers of inflammation (fibrinogen, D-dimer, urea, ferritin, LDH, CRP, and IL-6) decreased (p < 0.05). Radiological findings improved (p < 0.0001). Mortality and LoS were inferior in the O3 group. | Severe COVID-19-19 pneumonia |
| Fernández-Cuadros et al., 2020 | Case reports | Four cases | Rectal ozone (100 ml) concentration of 35 μg/ml for 5–10 days, | Reduction after treatment of IL-6, CRP, D dimer, SpO2% and LDH | Severe bilateral pneumonia |
| Hernández et al., 2021 | Prospective case control study | Nine AHT+ SOC (beginning the day of admission) VS 9 only SOC (control group). | AHT 200 ml of O2-O3 mixture. Concentration: 40 μg/ml; twice per day, for 4 days | Shorter time to clinical improvement | Severe pneumonia |
| Shah et al., 2021 | RCT | Thirty (rectal insufflation and minor AHT + SOC) VS 30 control group (only SOC) | Rectal ozone 150 ml concentration 40 μg/ml about twice daily +2–3 ml venous blood along with 5 ml ozone at 25 μg/ml [minor AHT] once daily for 10 days | Significant improvement in the mean values of all parameters tested (SpO2, LDH, ferritin, CRP); changes in clinical symptoms (p < 0.05) and inferior requirement for intensive care (p < 0.05). | Sixty patients with mild to moderate COVID-19 19 |
AHT, auto-hemotherapy; ICU, intensive care unit; SOC, standards of care; CRP, C reactive protein; LDH, lactate dehydrogenase; SpO2%, percentage of oxygen saturimetry; LoS, length of stay; and RCT, randomized controlled trial.