Rectal ozone therapy in high-risk symptomatic SARS-CoV-2 positive patients

INTERVENTION: Administration, Oral Administration, Rectal Anti‐Bacterial Agents Anti‐Infective Agents Ceftriaxone Chloroquine Group 1 Ozone (experimental). Rectal ozone therapy + Cuban national action protocol for Covid‐19. Version 1.6.. Ozone therapy: It will be applied by rectal insufflation according to the following scheme Day 1: 100 mL of gas with 30 µg / mL of Ozone concentration, (3 mg of ozone) every 12 hours Day 2: 150 mL of gas with 35 µg / mL of Ozone concentration, (5.25 mg of ozone) every 12 hours Day 3‐10: 200 mL of gas with 40 µg / mL of Ozone concentration, (8 mg of ozone) every 12 hours. The treatment will finish with 20 sessions of rectal ozone therapy for 10 days. Cuban national action protocol for Covid‐19. Version 1.6: Heberfer?n ® Interferon a‐2b recombinant + Interferon gamma recombinant, according to the national form 3, 5 M IU, by intramuscular route, every three days, it is administered one day, two days are waited and it is applied again. Kaletra: 2 tablets every 12 hours, for 10 days. Chloroquine 1 tablet every 12 hours, for 10 days. Broad spectrum antibiotics if you suspect bacterial over‐infection (Ceftriaxone 1gr to 2gr every 12 hours: in patients where associated bacterial infection is diagnosed. The decision to use another antibiotic will be determined by the results of laboratory studies and the microbiological map of the service). Treatment of comorbidities, according to their compensation status. Group 2 Conventional therapy (Control). Cuban national action protocol for Covid‐19. Version 1.6. This therapy is compound by: Heberfer?n ® Interferon a‐2b recombinant + Interferon gamma recombinant, according to the national form 3, 5 M IU, by intramuscular route, every three days, it is administered one day, two days are waited and it is applied again. Kaletra: 2 tablets every 12 hours, for 10 days. Chloroquine 1 tablet eve Injections, Intramuscular Insufflation Interferon‐alpha Interferon‐gamma Interferons Kaletra, Ozonetherapy Tablets CONDITION: Betacoronavirus Coronaviridae Infections Coronavirus Infections COVID‐19 COVID‐19 ; COVID‐19 ; SARS‐CoV2 Nidovirales Infections SARS Virus SARS‐CoV2 INCLUSION CRITERIA: 1) Hospitalized patients 2) between 19 and 80 years of age, 3) of both sexes 4) with a confirmed diagnosis of COVID‐19 by TR‐PCR. 5) That they have signed the informed consent to participate in the study. 6) Reported care patients with high risk mild and moderate symptoms according to hospital diagnostic criteria. High‐risk patient (RA): patient 65 years of age or older, with or without comorbidities, and patient under 65 years of age with comorbidities. PRIMARY OUTCOME: 1‐ RT‐PCR (Negativization of the test) (Positive or negative). Measurement time: Baseline, on the 5th, 7th and 10th days of treatment. ; 2‐ Clinical signs (mild, moderate, severe, critical). Measurement time: Every day until finalizing the treatment. Will be classified as:; Mild: Fever, cough, sore throat, nasal congestion, slight headache, general malaise, diarrhea and / or vomiting. Normal radiology. Oxygen saturation greater than 95%.; Moderate: Fever, cough, polypnea, slight changes in the Rx or lung ultrasound. Oxygen saturation greater than or equal to 90%.; Severe: Fever, cough, polypnea, infiltrate / condensation Rx or lung ultrasound. Oxygen saturation less than 90% or requires VAM.; Critical: ARDS, Sepsis or Septic Shock.; 3‐ Evolution of the symptom (the same, better or worse). Measurement time: Every day until finalizing the treatment. ; 4‐ Dyspnea (dysnea scale using the BORG method). Measurement time: Every day until finalizing the treatment. ; 5‐ Oximetry (determination by digital oximetro). Measurement time: Every day until finalizing the treatment. SECONDARY OUTCOME: 1‐ C‐reactive protein (mg/L). Measurement time: at Baseline, on the 5th, 7th and 10th days of treatment. ; 2‐ Dimero‐D (ng/mL). Measurement time: at Baseline, on the 5th, 7th and 10th days of treatment. ; 3‐ Serum ferritin (ng/ml). Measurement time: at Baseline, on the 5th, 7th and 10th days of treatment. ; 4‐ Redox Balance Indicator: Malondialdehyde (mmol/mgHb), PAOP (mM/cloramina T), Nitric Oxide (uM); Glutathione (mM/mgHb), dismutase superoxide (U/mhHb min) and catalase (U/mgHb min). Measurement time: at Baseline, on the 5th, 7th and 10th days of treatment. ; 5‐ Hemogram: hemoglobin (g/L), hematocrit (%), red blood cells (erythrocytes) (x106/L), white blood cells (leukocytes) (x106/L), platelets (x109/L)and mean platelet volume (ft) and differential of leukocytes (lymphocytes (%), monocytes (%), basophils (%), eosinophils (%) and neutrophils (%), erythrocyte sedimentation (mm/h). Measurement time: Baseline, on the 5th, 7th and 10th days of treatment.; 6‐ Blood biochemical: Lactate dehydrogenase (U/L), alanine amino transferase (U/L), aspartate amino transferase (U/L), creatinine kinase (mmol/L), gamma‐glutamyl transferase (U/L), glucose (mmol/L), creatinine (umol/L), biliribine (umol/L), uric acid (mg/dL). Measurement time: Baseline, on the 5th, 7th and 10th days of treatment. ; 7‐ Chest X‐ray (an evaluation scale will be classify inflammatory lung damage. Measuremetn time: Baseline and progressively according to the criteria of the attending physician.; 8‐ Intestinal microbiota (positive or negative). Measurement time: Baseline, on the 5th and 10th days of treatment.