Ozone therapy for patients with COVID-19 pneumonia: a Quasi-Randomized Controlled Trial

Abstract

Importance Aside from supportive management, there remains no specific treatment for Coronavirus Disease 2019 (COVID-19). Objective: Determine whether ozonated autohemotherapy is associated with a shorter time to clinical improvement in patients with severe COVID-19 pneumonia. Design: Single-center proof-of-concept prospective cohort study. Setting: Internal Medicine ward at Policlinica Ibiza Hospital, Spain. Participants: Eighteen consecutive patients with laboratory confirmed COVID-19 infection and severe pneumonia who were admitted to hospital between 20th March and 19th April 2020. Exposures: Patients in the ozonated autohemotherapy arm received hemotherapy twice daily starting on the day of admission for a median of 4 days. Each treatment involved administration of 200 mL autologous whole blood enriched with 200 mL of oxygen-ozone mixture with a 40 μg/mL ozone concentration. Patients in the control arm received supportive care. Assignment to hemotherapy versus usual care was determined based on the admitting physician on the day of admission, with only one of the three possible physicians prescribing ozonated autohemotherapy Main Outcomes: The primary outcome was time from hospital admission to clinical improvement, which was defined as either hospital discharge or a two-point improvement in clinical status measured on a six-point ordinal scale. Secondary outcomes were clinical improvement measured on the 7th, 14th and 28th day after admission, as well as time to a 2-fold reduction in concentrations of C-protein reactive, ferritin, D-dimer and lactate dehydrogenase. Results: The mean age of the cohort was 68 y and 72% (n=13) were male. Nine patients (50%) received ozonated autohemotherapy beginning on the day of admission. In unadjusted comparisons, ozonated autohemotherapy was associated with significantly shorter time to clinical improvement (median [IQR]), 7 days [6-10] vs 28 days [8-31], p=0.04) and significantly higher proportion of patients achieving 14-day clinical improvement (88.8% vs 33.3%, p=0.01). In risk-adjusted analyses, ozonated autohemotherapy was associated with a shorter mean time to clinical improvement (-11.3 days, p=0.04, 95% CI -22.25 to -0.42). Conclusions and Relevance: Ozonated autohemotherapy was associated with a significantly shorter time to clinical improvement in this prospective cohort study. Given the small sample size and single-center study design, these observations require evaluation in larger randomized controlled trials.

Ozone Preconditioning: Waking up the dragon

“…Ozone has virtually no side effects and does not induce microbial resistance patterns like pharmacologic therapies [267]. Numerous studies affirm ozone's efficacy and safety in Covid-19 disease [267][268][269][270][271][272][273][274][275][276][277][278][279][280][281]. Thorp et al describe mechanisms by which ozone therapy affects Covid-19 outcomes: increased antioxidant production, induction of Nrf2-and HO-1-mediated nuclear mechanisms, down-regulation of pro-inflammatory immune pathways, direct toxic viral effects, inhibition of viral replication and increased blood and tissue oxygenation [279].…”

“…Ozone therapy reduced viral titers and improved clinical symptoms in Covid-19-infected ICU patients [280]. Other studies found that ozone shortened time-lines for clinical improvement [281]. Since ozone confers protection against organ-injury in ischemia-reperfusion injury it only stands to reason that it should prevent or mitigate multi-system organ failure associated with advanced Covid-19 infection if administered in a time-sensitive manner.…”

Science's Response to CoVID‐19

“…Oxygen/ozone therapy (another treatment known to promote antioxidant response) has also been proposed to help protect against ischemia‐reperfusion injury and other pathological manifestations of severe CoVID‐19 [302] . Some reports on small cohorts of patients have reported numerical, but not statistically‐significant effects of ozone on CoVID‐19; [302] others, with similarly small numbers of people have reported positive effects [303] …”

Science’s Response to COVID-19

“…301 Some reports on small cohorts of patients have reported numerical, but not statistically-significant effects of ozone on CoVID-19; 301 others, with similarly small numbers of people have reported positive effects. 302 A recent study showed numerous pathways rewired upon CoVID-19 infection, including processing mRNA and several metabolic elements, including nucleic acid metabolism pathways. Inhibition of proteins identified in such pathways (albeit often by compounds not in clinical use) appeared to inhibit viral proliferation, although the effects on host cells were not thoroughly investigated.…”