Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset—Lessons Learned

After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes.     

瑞德西韦对狂犬病病毒的体外抑制作用研究北大核心CSCD

目的研究瑞德西韦对不同狂犬病病毒的体外抑制作用。方法根据药物、病毒及细胞的不同作用方式,以法匹拉韦(T705)作为阳性对照药物,使用组织培养半数感染量(TCID_(50))、直接免疫荧光法及实时荧光定量PCR等方法,分析瑞德西韦对不同狂犬病病毒的阻断吸附、抑制复制和直接杀伤作用。结果在阻断吸附和抑制复制的实验中,与相应浓度的T705阳性对照组相比,500μmol/L瑞德西韦处理BHK-21及N2a细胞后,CVS-11病毒滴度均降低(P<0.01)。分别与CVS-11及SC16街毒株感染组相比,500μmol/L瑞德西韦处理N2a细胞后病毒的滴度及mRNA拷贝数均降低(P<0.01)。在直接杀伤实验中,瑞德西韦无抑制病毒作用。结论瑞德西韦能够显著阻断狂犬病病毒的吸附并能够抑制其体外复制,但无直接杀伤狂犬病病毒的能力。     

Remdesivir for COVID‐19 pneumonia in patients with severe chronic kidney disease: A Case series and review of the literature

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID‐19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.