Joint Research Centre (JRC), European Commission, Ispra, Italy.
London School of Hygiene & Tropical Medicine, University of London, London, UK.
J R Soc Interface. 2024 Nov;21(220):20240536. doi: 10.1098/rsif.2024.0536. Epub 2024 Nov 27.
The effectiveness of antiviral treatment with remdesivir against COVID-19 has been investigated in clinical trials suggesting earlier recovery. However, this effect seems to be rather modest. In this study, we tracked the clinical course of SARS-CoV-2 infections in 369 COVID-19 individuals across a spectrum of illness severities, including both untreated individuals and individuals who received antiviral treatment with remdesivir. Moreover, using a process-based mathematical model, we quantified and analysed the within-host infection dynamics of a total of 88 individuals, of which 69 were untreated and 19 antiviral-treated individuals. For untreated individuals, we found that those hospitalized exhibit lower levels of early immune response and higher cumulative viral loads than those who were not. For treated individuals, we found that those who died were on average hospitalized later after symptom onset than those who survived, underscoring the importance of early medical intervention for severe COVID-19. Finally, our model estimates a rather limited antiviral activity of remdesivir. Our results provide valuable insights into the clinical course of COVID-19 during antiviral treatment with remdesivir and suggest the need for alternative treatment regimens.
瑞德西韦治疗 COVID-19 的疗效已在临床试验中得到证实，提示可更早恢复。然而，这种效果似乎相当有限。在这项研究中，我们追踪了 369 例 COVID-19 患者的临床病程，涵盖了疾病严重程度的广泛范围，包括未经治疗的患者和接受瑞德西韦抗病毒治疗的患者。此外，我们使用基于过程的数学模型，对总共 88 例患者的体内感染动态进行了量化和分析，其中 69 例未接受治疗，19 例接受了瑞德西韦抗病毒治疗。对于未接受治疗的患者，我们发现住院患者的早期免疫反应水平较低，累积病毒载量较高。对于接受治疗的患者，我们发现死亡患者的平均住院时间比存活患者晚，这凸显了早期医疗干预对严重 COVID-19 的重要性。最后，我们的模型估计瑞德西韦的抗病毒活性相当有限。我们的研究结果为瑞德西韦抗病毒治疗期间 COVID-19 的临床病程提供了有价值的见解，并提示需要替代治疗方案。
