Efficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study

Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran's Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials. Funding: Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). Clinical trial number: NCT04661930

Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies.

CAPRISA, 2015.Abstract available in pdf

A saúde neonatal na perspectiva de atenção contínua à saúde da mulher e da criança La atención neonatal en la perspectiva de la atención continua a la salud de las mujeres y niños The neonatal care from the perspective of continuous attention to woman and child's health

O estudo é uma revisão narrativa de teses e dissertações concluídas no período de 2000 a 2009 produzidas pelo Grupo de Pesquisa Enfermagem Obstétrica e Neonatal e pelo Núcleo de Estudos e Pesquisa em Aleitamento Materno da Escola de Enfermagem da Universidade de São Paulo que focalizaram os fatores maternos e perinatais que repercutem na saúde neonatal. A produção científica evidencia alinhamento com as diretrizes estabelecidas pelos órgãos de saúde nacionais e internacionais para a promoção da saúde neonatal e infantil.<br>El estudio es una revisión de la literatura de tesis y disertaciones producidas en el periodo de 2000 hasta 2009 por el Grupo de Investigación de Enfermería Obstétrica y Neonatal y por el Centro de Estudios y Investigación en Lactancia Materna de la Escuela de Enfermería de la Universidad de São Paulo, que se centró en las repercusiones maternas y perinatales en la salud del recién nacidos. La producción científica se muestra de acuerdo con las directrices para promover la salud neonatal y infantil establecidas por los organismos de salud nacionales e internacionales.<br>The study is a literature review of theses and dissertations concluded from 2000 to 2009 developed by the Obstetric and Neonatal Nursing Research Group and Breastfeeding Center for Studies and Research of Nursing School, University of São Paulo, which focused on the maternal and perinatal impact on neonatal health. The scientific production shows agreement with the guidelines to promote neonatal and infant health established by national and international health agencies