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 ).
Subject(s)
COVID-19 , Fenofibrate , Humans , Female , Adult , Middle Aged , Aged , Male , SARS-CoV-2 , Fenofibrate/therapeutic use , Lipid Metabolism , PPAR alphaABSTRACT
Introducción: la enfermedad por arañazo de gato(EAG) en la mayoría de las veces es descrita en su forma típica, las formas sistémicas son raras y de escaso reporte. La EAG puede tener una gran variedad de presentaciones, siendo algunas de ellas poco frecuentes. Es la primera vez que se reporta esta forma de presentación en el Perú. Caso clínico: presentamos aquí dos niñas de cinco y seis años de edad, hospitalizadas en el Servicio de Pediatría del HNCASE EsSalud Arequipa. Con formas sistémicas de enfermedad por arañazo de gato. Las niñas fueron arañadas por gatos cachorros sin reacción local, las cuales presentaron fiebre prolongada, malestar general, anorexia, cefalea, dolor abdominal, compromiso de ganglios, hepatomegalia y esplenomegalia, velocidad de eritrosedimentación globular (VSG) acelerada, proteína C reactiva (PCR) elevada, leucocitosis, desviación izquierda, transaminasas hepáticas discretamente elevadas o normales, en ambas se confirma el diagnóstico con la reacción serológica positiva (IgG e IgM) para Bartonella henselae y microabscesos hepatoesplénicos en la TAC abdominal. En ambas el tratamiento antibiótico combinado con macrólido más rifampicina por un mes tuvo eficacia terapéutica.
Introduction: Cat-scratch disease most of the times is described reporting its typical form; systemic forms are rare and they are seldom reported. Cat-scratch disease may have a great variety of presentations, and some of them are quite unusual. This is the very first time that the systemic form is reported in Peru. Clinical case: We present two girls, 5 and 6 years old, hospitalized in the pediatric ward of Hospital Nacional Carlos Alberto Seguin, EsSalud, Arequipa, Peru, who presented with the systemic form of cat scratch disease. Both girls were scratched by kittens without developing a characteristic local reaction, and they presented with prolonged fever, malaise, anorexia, headache, abdominal pain, lymph node enlargement, liver and spleen involvement, accelerated erythrocyte sedimentation rate, high levels of C-reactive protein, leukocytosis, left shift, slightly elevated or normal liver enzymes; and in both girls the diagnosis was confirmed with a positive result in serological testing (IgG and IgM) for Bartonella henselae. Also, some splenic microabscesses were found in the CT scan. Both girls responded to antimicrobial therapy using a macrolide combined with rifampin for one month.
