Evaluation of a five-layer hydrocellular polyurethane foam dressing across wound care settings in southern Europe.

OBJECTIVE: The burden of chronic wounds did not disappear during the Covid-19 pandemic, so new ways to address healthcare practitioner (HCP) education had to evolve. The Teach, Try, and Talk (T3) programme was conceived in 2021 with HCPs in southern Europe (Italy, Spain and Portugal). METHOD: Virtual education sessions with experienced HCP guest speakers were held and a five-layer hydrocellular polyurethane foam dressing (HPFD) was introduced as a way of reducing dressing change frequencies and improving clinician satisfaction. HCPs recorded their experience of the HPFD using an online form and participated in a further virtual session with experienced HCPs to discuss the results. RESULTS: There were a total of 190 responses. A significant dressing change reduction from 3.6 changes per week to 1.8 with the HPFD (p<0.001) was observed in Italy, Spain and Portugal and within different care settings (hospital, wound clinic/health centre and the patient's home). Nearly one-third of participants stated one more day of dressing wear time was achieved by the ability of the HPFD to lock in and manage exudate, with nearly a quarter of responses stating it was due to fewer than three dressing lobes being full. The majority (97.8%) of HCPs stated they would recommend the HPFD to colleagues and patients. CONCLUSION: The T3 programme is a highly successful method of training delivery and practice improvement across a variety of healthcare settings in southern Europe, helping support HCP engagement and ongoing development in challenging times during the Covid-19 pandemic. The programme can be adapted considering the needs of different HCPs and payor and/or healthcare systems.

Effect of remdesivir on mortality rate and clinical status of COVID-19 patients: a systematic review with meta-analysis.

Remdesivir (RDV) is a broad-spectrum antiviral drug, now approved by Regulatory Agencies for COVID-19 treatment. RDV is associated with improvements in clinical outcomes, but no conclusive studies have shown an effect in reducing mortality. This study aimed to carry out a systematic review with meta-analysis to investigate whether RDV can significantly modify the outcome of COVID-19 patients evaluating its effects on mortality, length of stay, time to clinical improvement and need for oxygen supplementation. No significant improvement in terms of survival in patients treated with standard therapy (ST)+RDV as compared to ST alone (P = 0.24) was found. The duration of oxygen support was significantly lower in patients treated with ST + RDV compared with ST alone (P = 0.03). Further investigations should be planned to assess the real impact of RDV in the management of COVID-19 patients.

EFFICACY AND SAFETY OF ULTRA-LOW DOSE INHALED MELPHALAN IN THE TREATMENT OF HOSPITALIZED PATIENTS WITH COVID-19

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need ofcreating the optimaltactics ofefficientandsafe anti-inflammatory therapy. Anew methodoftreatment ofCOVID-19withinhalation ofultra-low (non-cytotoxic)doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma. The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage. Materials andmethods. A prospective, open, controlled, blindfor the centralexpert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients ofthe control group were selectedby an independentexpertretrospectively using the computer algorithm for selecting“close” patients based on the “case-control” principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning ofinhalations in the melphalan group andfrom the corresponding day in the control group. Results. Inhalations of melphalan led to a significant improvement in the clinical condition ofpatients according to the WHOscale, decrease in the intensity ofdyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group. Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage. © 2022 by the Author(s).

Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone.

Objectives: This retrospective cohort study aims to explore head-to-head clinical outcomes and complications associated with tocilizumab or baricitinib initiation among hospitalized COVID-19 patients receiving dexamethasone. Methods: Among 10,445 COVID-19 patients hospitalized between January 21st 2020 and January 31st 2021 in Hong Kong, patients who had received tocilizumab (n = 165) or baricitinib (n = 76) while on dexamethasone were included. Primary study outcome was time to clinical improvement (at least one score reduction on WHO clinical progression scale). Secondary outcomes were disease progression, viral dynamics, in-hospital death, hyperinflammatory syndrome, and COVID-19/treatment-related complications. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. Results: The initiation of tocilizumab or baricitinib had no significant differences in time to clinical improvement (HR = 0.86, 95%CI 0.57-1.29, p = 0.459), hospital discharge (HR = 0.85, 95%CI 0.57-1.27, p = 0.418), recovery without the need for oxygen therapy (HR = 1.04, 95%CI 0.64-1.67, p = 0.883), low viral load (HR = 1.49, 95%CI 0.85-2.60, p = 0.162), and positive IgG antibody (HR = 0.97, 95%CI 0.61-1.54, p = 0.909). Time to viral clearance (HR = 1.94, 95%CI 1.01-3.73, p = 0.048) was shorter in the tocilizumab group with marginal significance, compared to that of baricitinib. Meanwhile, the two treatment modalities were not significantly different in their associated risks of in-hospital death (HR = 0.63, 95%CI 0.29-1.35, p = 0.233), severe liver injury (HR = 1.15, 95%CI 0.43-3.08, p = 0.778), acute renal failure (HR = 2.33, 95%CI 0.61-8.82, p = 0.213), hyperinflammatory syndrome (HR = 2.32, 95%CI 0.87-6.25, p = 0.091), thrombotic and bleeding events (HR = 1.39, 95%CI 0.32-6.00, p = 0.658), and secondary infection (HR = 2.97, 95%CI 0.62-14.31, p = 0.173). Conclusion: Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications, hyperinflammatory syndrome, thrombotic and bleeding events, and secondary infection. On the other hand, tocilizumab users might achieve viral clearance slightly faster than baricitinib users. Further studies and clinical trials are needed to confirm our findings regarding the evaluation of tocilizumab and baricitinib in COVID-19 patients with different disease severities, at varying stages or timing of drug initiation, and considering the concomitant use of other therapeutics.

Remdesivir: an overview of patenting trends, clinical evidence on COVID-19 treatment, pharmacology and chemistry.

By December 2021, the COVID-19 caused approximately 6.1 million deaths around the world. Several vaccines have been approved, but there is still a need for non-prophylactic treatments for COVID-19. Remdesivir is an antiviral drug approved for emergency use against COVID-19 in several countries, but one of the first clinical trials was inconclusive about the mortality reduction, although the drug showed a reduction in the recovery time of hospitalized patients. Thus, the present investigation revisits the clinical evidence of using remdesivir for COVID-19 treatment, patent status, pharmacology and chemistry. We found 184 families of patents in the Cortellis database, and concerning the clinical evidence, we retrieved 14 systematic reviews with meta-analysis involving remdesivir as a treatment for COVID-19, discussing the reduction of adverse events, hospitalization days, mortality rate and the mechanical ventilation period.

Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19.

Background: Evidence-based therapies used to treat coronavirus disease (COVID-19) remain limited. Azoximer bromide (AZB; Polyoxidonium®) is an immunomodulating molecule frequently used in the Russian Federation. It offers demonstrable therapeutic benefit in upper respiratory tract infections. This study evaluated the safety and efficacy of AZB when used in combination with standard of care treatment in patients hospitalized with COVID-19. Methods: Hospitalized patients with COVID-19 (n=81; nine sites) received AZB 12 mg intravenously once daily for 3 days then intramuscularly every other day until day 17. The primary endpoint included clinical status at day 15 versus baseline. Historical control data of 100 patients from a randomized, controlled, open-label trial conducted in China were included to serve as a direct control group. Results: Notable clinical improvement, assessed by seven-point ordinal scale (OS) score and National Early Warning Score, was observed. Mean duration of hospitalization was 19.3 days. Indicators of pneumonia and lung function showed gradual recovery to normalization. No patients died but, by day 28, one patient still required respiratory support; this patient died on day 34. A higher proportion of patients receiving AZB required invasive or non-invasive ventilation (OS 5 or 6) at baseline compared with the historical control group. Improvement in mean OS score by day 14/15 was not notable in the control group (OS 3.99-3.87) but was clear in the AZB group (OS 4.36-2.90). Mean duration of hospitalization was similar in the control group (16.0 days); however, day 28 mortality was higher, at 25.0% (n=25). Conclusion: AZB combined with standard of care was safe and well tolerated. An apparent clinical improvement could not be fully evaluated due to the lack of a direct control group; further assessment of AZB for the treatment of COVID-19 in a randomized, placebo-controlled study is warranted.

Optimal Timing of Remdesivir Initiation in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Administered With Dexamethasone.

BACKGROUND: Evidence is lacking about any additional benefits of introducing remdesivir on top of dexamethasone, and the optimal timing of initiation. METHODS: In a territory-wide cohort of 10 445 coronavirus disease 2019 (COVID-19) patients from Hong Kong who were hospitalized between 21 January 2020 and 31 January 2021, 1544 had received dexamethasone during hospitalization. The exposure group consisted of patients who had initiated remdesivir prior to dexamethasone (n = 93) or co-initiated the 2 drugs simultaneously (n = 373), whereas the nonexposure group included patients who were given remdesivir after dexamethasone (n = 149) or those without remdesivir use (n = 929). Multiple imputation and inverse probability of treatment weighting for propensity score were applied and hazard ratios (HRs) of event outcomes were estimated using Cox regression models. RESULTS: Time to clinical improvement (HR = 1.23; 95% CI, 1.02-1.49; P = .032) and positive IgG antibody (HR = 1.22; 95% CI, 1.02-1.46; P = .029) were significantly shorter in the exposure group than that of nonexposure. The exposure group had a shorter hospital length of stay by 2.65 days among survivors, lower WHO clinical progression scale scores from 5 days of follow-up onwards, and lower risks of in-hospital death (HR = .59; 95% CI, .36-.98; P = .042) and composite outcomes; and without experiencing an increased risk of acute respiratory distress syndrome. Differences in the cumulative direct medical costs between groups were no longer significant from 17 days of follow-up onwards. CONCLUSIONS: Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.

Clinical Improvement, Outcomes, Antiviral Activity, and Costs Associated With Early Treatment With Remdesivir for Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Evidence remains inconclusive on any significant benefits of remdesivir in patients with mild-to-moderate COVID-19. This study explored the disease progression, various clinical outcomes, changes in viral load, and costs associated with early remdesivir treatment among COVID-19 patients. METHODS: A territory-wide retrospective cohort of 10 419 patients with COVID-19 hospitalized from 21 January 2020 to 31 January 2021 in Hong Kong was identified. Early remdesivir users were matched with controls using propensity-score matching in a ratio ≤1:4. Study outcomes were time to clinical improvement of at least 1 point on WHO clinical progression scale, hospital discharge, recovery, viral clearance, low viral load, positive IgG antibody, in-hospital death, and composite outcomes of in-hospital death requiring invasive ventilation or intensive care. RESULTS: After multiple imputation and propensity-score matching, median follow-up was 14 days for both remdesivir (n = 352) and control (n = 1347) groups. Time to clinical improvement was significantly shorter in the remdesivir group than that of control (HR: 1.14; 95% CI: 1.01-1.29; P = .038), as well as for achieving low viral load (1.51; 1.24-1.83; P < .001) and positive IgG antibody (1.50; 1.31-1.70; P < .001). Early remdesivir treatment was associated with lower risk of in-hospital death (HR: .58; 95% CI: .34-.99; P = .045), in addition to a significantly shorter length of hospital stay (difference: -2.56 days; 95% CI: -4.86 to -.26; P = .029), without increasing risks of composite outcomes for clinical deterioration. CONCLUSIONS: Early remdesivir treatment could be extended to hospitalized patients with moderate COVID-19 not requiring oxygen therapy on admission.

Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19.

BACKGROUND AND AIMS: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. METHODS: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. RESULTS: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, -3 (-4 to -1), p = 0.022], reduction in duration of fever [-1.0 (-2.0 to 0.0), p = 0.025], viral shedding [-3 (-6 to -1), p < 0.001], and hospital stay [-3 (-5 to -1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. CONCLUSION: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis.

AIMS: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. METHODS: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. RESULTS: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. CONCLUSION: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed.The reviews of this paper are available via the supplemental material section.

Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited. METHODS: We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes. RESULTS: Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19-5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69-6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17-7.80) than on day 7 (OR = 1.60, 95% CI = 1.03-2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group. CONCLUSIONS: Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.

Clinical effectiveness of drugs in hospitalized patients with COVID-19: a systematic review and meta-analysis.

The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection. We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization, virological clearance, and severe adverse events. A total of 48 studies were retrieved from the databases. Eleven articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir. We can conclude that dexamethasone would have a better result in hospitalized patients, especially in low-resources settings. The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries, since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources.The reviews of this paper are available via the supplemental material section.

Predictors associated with clinical improvement of SARS-CoV-2 pneumonia.

BACKGROUND: There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. OBJECTIVES: This study aimed to investigate the factors associated with the clinical improvement of COVID-19. METHODS: Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. RESULTS: Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002-1.114), no hypertension (HR, 2.077; 95% CI, 1.006-4.287), and low D-dimer levels (<1 µg/ml) (HR, 2.372; 95% CI, 1.229-4.576) were confirmed to be significant predictive factors for time to clinical improvement. Furthermore, a lower SARS-CoV-2 RNA copy number was also a predictive factor for clinical improvement. CONCLUSIONS: Several predictors for the clinical improvement of COVID-19 pneumonia were identified. These results may be important for the management of COVID-19 pneumonia.

Current Evidence of Interleukin-6 Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background: Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence. Methods: Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries (clinicaltrials.gov), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0. Results: Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45-0.84, p = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70-2.08, p = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42-1.33, p = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95-3.61, p = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate. Conclusion: IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.

COVID-19 convalescent plasma treatment of moderate and severe cases of SARS-CoV-2 infection: A multicenter interventional study.

OBJECTIVE: To study the effectiveness of COVID-19 convalescent plasma (CCP) therapy for patients with moderate and severe COVID-19 disease. METHODS: This non-randomized prospective cohort study was conducted from May 21 to June 30, 2020, at four major tertiary hospitals in Kuwait. CCP was administered to 135 patients. The control group comprised 233 patients who received standard treatment. All patients (N = 368, median age 54 [range 15-82]) had laboratory-confirmed SARS-CoV-2 infection and either moderate or severe COVID-19 disease. RESULTS: CCP treatment was associated with a higher rate of clinical improvement in patients with moderate or severe disease. Among those with moderate COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 8 days in the control group (p = 0·006). For severe COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 15.5 days in the control group (p = 0·003). In the adjusted analysis, patients with moderate disease treated with CCP had a significantly lower 30-day mortality rate. Compared to the control group, oxygen saturation improved within 3 days of CCP transfusion, and lymphocyte counts improved from day 7 in patients with moderate COVID-19 disease and day 11 in patients with severe disease. C-reactive protein levels declined throughout the first 14 days after CCP transfusion. None of the CCP patients developed a serious transfusion reaction. CONCLUSIONS: The data show that administration of CCP is a safe treatment option for patients with COVID-19 disease with a favorable outcome in the rate of, and time to, clinical improvement.

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.