publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.Cómo citar este artículo: Hernández A, et al. Dos terapias conocidas podrían ser efectivas como adyuvantes en el paciente crítico infectado por COVID PALABRAS CLAVE COVID-19; SARS-CoV-2; Vitamina C; OzonoResumen La neumonía causada por coronavirus, que se originó en Wuhan, China, a finales de 2019, se ha extendido por todo el mundo convirtiéndose en una pandemia. Desafortunadamente, a día de hoy no existe ninguna vacuna específica para el virus COVID-19, y el tratamiento está siendo de soporte con añadido de antivirales y otros fármacos, sin que hasta la fecha se haya evidenciado un beneficio claro. Muchos de estos pacientes se deterioran rápidamente y requieren ser intubados y ventilados mecánicamente, lo que está provocando el colapso del sistema sanitario en muchos países debido a la falta de ventiladores y de camas de críticos.En este documento revisamos dos terapias adyuvantes sencillas de aplicar, sin efectos deletéreos y de un coste bajo que podrían ser de utilidad para el tratamiento de la infección por coronavirus agudo severo asociado al síndrome respiratorio agudo (SARS-CoV-2). La vitamina C, un potente antioxidante, se ha convertido en una terapia relevante debido a sus beneficios potenciales cuando se administra por vía intravenosa. El efecto potencial de la vitamina C en la reducción de la inflamación en los pulmones podría desempeñar un papel clave en la lesión pulmonar causada por la infección por coronavirus. Otra posible terapia eficaz es el ozono. Pese a la controversia que siempre le ha acompañado, se ha estudiado y utilizado ampliamente durante muchos años y su eficacia se ha demostrado en múltiples estudios. Sin embargo, nuestro objetivo no es hacer una revisión exhaustiva de dichas terapias sino difundir sus efectos beneficiosos. * Autor para correspondencia. Correo electrónico: albimar23@yahoo.es (A. Hernández). Cómo citar este artículo: Hernández A, et al. Dos terapias conocidas podrían ser efectivas como adyuvantes en el paciente crítico infectado por COVID
BACKGROUND Aside from supportive management, there remains no specific treatment for Coronavirus Disease 2019 (COVID-19). OBJECTIVE Determine whether the use of ozonated autohemotherapy is associated with shorter time to clinical improvement in patients with severe COVID-19 pneumonia. METHODS 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. 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 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. CLINICALTRIAL NCT04444531
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.
Introduction While there are no pharmacological treatments with proven efficacy for coronavirus disease 2019 (COVID-19), tocilizumab has emerged as a candidate therapy. Some aspects of this therapy are still unknown, including the optimal timing of administration. Objective This observational study aimed to compare the 90-day mortality in two cohorts of patients when the drug was administered within the first 10 days from onset of symptoms or after day 11. Methods Patients hospitalised with severe COVID-19 pneumonia who had received tocilizumab were divided into two groups according to when the medication was administered. The primary outcome was 90-day mortality. Secondary outcomes were 30-day mortality, clinical improvement on a 6-item scale by day 6, biomarker improvement by day 6, radiological image improvement by day 10 and SaO 2 quotient by day 6. The results in the two groups were compared. Additionally, adverse events relating to tocilizumab were recorded. Results A total of 112 patients were analysed. Both groups were epidemiologically comparable. The results obtained in the primary efficacy variable of the study (90day mortality) showed a statistically significant difference in the subgroups according to the time of administration of tocilizumab (18.6% vs 5.0%, p=0.048). There was clinical improvement in 24.1% of patients at 6 days, with similar behaviour in both subgroups. No statistically significant differences were found in the percentage of patients who achieved radiological improvement at 10 days or in the other inflammatory parameters, with the exception of significant reductions in lactate dehydrogenase and C-reactive protein. Administration of tocilizumab was not associated with relevant adverse events. Conclusion To our knowledge, this is the first report of data regarding the timing of administration of tocilizumab in patients with COVID-19 pneumonia. A strategy involving tocilizumab administration after 10 days from onset of symptoms may decrease mortality. Further randomised controlled trials are needed to confirm this emerging hypothesis.
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