ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).
ABSTRACT
El uso de Plasma de Convaleciente de COVID-19 (PC-CoV19) como coadyuvante en el tratamiento de pacientes, tendría impacto socioeconómico importante al disminuir el periodo de estancia hospitalaria y letalidad por la enfermedad. La determinación de anticuerpos en plasma de potenciales donantes es criterio fundamental para su selección. Existe dificultad para disponer de pruebas serológicas certificadas que cuantifiquen anticuerpos específicos contra SARS-CoV-2. Las Pruebas de Diagnóstico Rápido (PDR) se convierten en herramienta útil y al alcance para la selección de pacientes recuperados, potenciales donantes de PC-CoV19. Este estudio evaluó el porcentaje de positividad de diferentes PDR en veintidós (22) muestras de pacientes con COVID-19 confirmada por RT-PCR. Las muestras se analizaron siguiendo el procedimiento descrito por cada fabricante. Se analizó el comportamiento de las PDR en pacientes sintomáticos y asintomáticos en diferentes momentos de la enfermedad. El porcentaje de positividad fue de 100% con dos de las tres pruebas utilizadas, una de las cuales discrimina IgM de IgG. Se concluye que la presencia de IgG se registra a partir de los 15 días del inicio de los síntomas y se mantiene presente a los 59 días de evolución en los pacientes sintomáticos, y que pacientes asintomáticos podrían ser considerados candidatos a donantes de PC-CoV19 pues se evidenció seroconversión para IgG. El porcentaje de positividad a IgG podría disminuir en los pacientes recuperados. Se sugiere que pacientes sintomáticos con criterio de alta médica sean considerados candidatos donantes en momento posterior a 28 días de la fecha de inicio de los síntomas. Se recomienda utilizar PDR que discriminen IgM de IgG como herramienta para la selección de donantes de PC-CoV19(AU) The use of COVID-19 Convales-cent Plasma (PC-CoV19) as an ad-juvant for the treatment of patients, would have a significant socioeconomic impact by reducing the leng-th of hospital stay and lethality due to the disease. The determination of antibodies in plasma from potential donors is a fundamental criterion for their selection. There is dificulty in obtaining certified serological tests that quantify specific antibodies against SARS-CoV-2. Rapid Diagnostic Tests (PDR) become a useful and accessible tool in the selection of recovered patients, potential PC-CoV19 donors. This study evaluated the positivity rate of different PDRs in twenty two (22) samples from patients with COVID-19 confirmed by RT-PCR. The samples were analyzed following the procedure described by each manufacturer. The performance of PDRs was analyzed in symptomatic and asymptomatic patients at different times of the disease. The positivity rate was 100% with two of the three tests used, one of which discriminates IgM from IgG. It is concluded that the presence of IgG is recorded 15 days after the onset of symptoms and remains present at day 59 of evolution in symptomatic patients, and that asymptomatic patients could be considered candidates for PC-CoV19 donors since IgG se-reconversion was evident. The positivity rate to IgG could decrease in the recovered patients. It is suggested that symptomatic patients with medical discharge criteria be considered donor candidates after 28 days from the date of onset of symptoms. It is recommended to use PDRs that discriminate IgM from IgG as a tool for the selection of PC-CoV19 donors
ABSTRACT
(1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κ B/Nrf2 pathways and IL-6/IL-1ß expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κ B/Nrf2 balance and IL-6 and IL-1ß expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.