Ozone therapy for patients with COVID-19 pneumonia: Preliminary report of a prospective case-control study.

BACKGROUND: There is still no specific treatment strategies for COVID-19 other than supportive management. DESIGN: A prospective case-control study determined by admittance to the hospital based on bed availability. PARTICIPANTS: Eighteen patients with COVID-19 infection (laboratory confirmed) severe pneumonia admitted to hospital between 20th March and 19th April 2020. Patients admitted to the hospital during the study period were assigned to different beds based on bed availability. Depending on the bed the patient was admitted, the treatment was ozone autohemotherapy or standard treatment. Patients in the case group received ozonated blood twice daily starting on the day of admission for a median of four 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. MAIN OUTCOMES: The primary outcome was time from hospital admission to clinical improvement. RESULTS: Nine patients (50%) received ozonated autohemotherapy beginning on the day of admission. Ozonated autohemotherapy was associated with shorter time to clinical improvement (median [IQR]), 7 days [6-10] vs 28 days [8-31], p = 0.04) and better outcomes at 14-days (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). CONCLUSION: Ozonated autohemotherapy was associated with a significantly shorter time to clinical improvement in this prospective case-control study. Given the small sample size and study design, these results require evaluation in larger randomized controlled trials. CLINICAL TRIAL REGISTRATION NUMBER: NCT04444531.

Potential Role of Oxygen-Ozone Therapy in Treatment of COVID-19 Pneumonia.

BACKGROUND Pneumonia caused by coronavirus originated in Wuhan, China in late 2019 and has spread around the world, becoming a pandemic. Many patients deteriorate rapidly and require intubation and mechanical ventilation, which is causing the collapse of healthcare systems in many countries. Coronavirus infection is associated with extensive lung inflammation and microvascular thrombosis, which can result in hypoxia. It can also cause severe and lasting harm in other organs, including the heart and kidneys. At present, there is no proven and efficacious treatment for this new disease. Consequently, there is a growing tendency to use novel methods. Ozone therapy consists of administration of a mixture of oxygen and ozone (a molecule consisting of 3 oxygen atoms). The potential benefits of this therapy include reduced tissue hypoxia, decreased hypercoagulability, renal and heart protection, modulated immune function, improved phagocytic function, and impaired viral replication. CASE REPORT We report rapidly improved hypoxia with associated decreases in inflammatory markers and D-dimer immediately after 1-4 sessions of oxygen-ozone (O2-O3) therapy in 3 patients with COVID-19 pneumonia who presented with respiratory failure. Invasive mechanical ventilation was not required in these 3 patients. All patients were discharged home on days 3-4 after O2-O3 therapy. CONCLUSIONS O2-O3 therapy appears to be an effective therapy for COVID-19 patients with severe respiratory failure. Large controlled clinical trials are required to study the efficacy and safety of using O2-O3 therapy compared with the standard supportive case in patients with COVID-19 in terms of the need for invasive ventilation and length of hospital and intensive care unit stays.

Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus.

OBJECTIVE: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO. METHODS: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays. RESULTS: Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10-77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4-13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3-2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001). CONCLUSIONS: In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.

Circadian oscillatory transcriptional programs in grapevine ripening fruits.

BACKGROUND: Temperature and solar radiation influence Vitis vinifera L. berry ripening. Both environmental conditions fluctuate cyclically on a daily period basis and the strength of this fluctuation affects grape ripening too. Additionally, a molecular circadian clock regulates daily cyclic expression in a large proportion of the plant transcriptome modulating multiple developmental processes in diverse plant organs and developmental phases. Circadian cycling of fruit transcriptomes has not been characterized in detail despite their putative relevance in the final composition of the fruit. Thus, in this study, gene expression throughout 24 h periods in pre-ripe berries of Tempranillo and Verdejo grapevine cultivars was followed to determine whether different ripening transcriptional programs are activated during certain times of day in different grape tissues and genotypes. RESULTS: Microarray analyses identified oscillatory transcriptional profiles following circadian variations in the photocycle and the thermocycle. A higher number of expression oscillating transcripts were detected in samples carrying exocarp tissue including biotic stress-responsive transcripts activated around dawn. Thermotolerance-like responses and regulation of circadian clock-related genes were observed in all studied samples. Indeed, homologs of core clock genes were identified in the grapevine genome and, among them, VvREVEILLE1 (VvRVE1), showed a consistent circadian expression rhythm in every grape berry tissue analysed. Light signalling components and terpenoid biosynthetic transcripts were specifically induced during the daytime in Verdejo, a cultivar bearing white-skinned and aromatic berries, whereas transcripts involved in phenylpropanoid biosynthesis were more prominently regulated in Tempranillo, a cultivar bearing black-skinned berries. CONCLUSIONS: The transcriptome of ripening fruits varies in response to daily environmental changes, which might partially be under the control of circadian clock components. Certain cultivar and berry tissue features could rely on specific circadian oscillatory expression profiles. These findings may help to a better understanding of the progress of berry ripening in short term time scales.