RESUMO
In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Citocinas , Epigênese Genética , Expressão Gênica , Humanos , Interleucina-6 , SARS-CoV-2/efeitos dos fármacosRESUMO
CAR-T THERAPY: CURRENT USE IN THE UNITED STATES IN 2018: Treatment with T-cells engineered with chimeric antigen receptors (CAR T-cell therapy) has been a field of intense research in the United States since the 1980s. The recent approval in August 2017 of Kymriah (tisagenlecleucel) opened the door to broader access to CAR T-cell therapy outside of clinical trials. Here, we aim to give the reader a practical summary of the current practices in the US when considering a patient for CAR T-cell therapy. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.