Department of Electrical & Computer Engineering, Storrs, 06269, USA.
Sci Rep. 2022 Apr 27;12(1):6873. doi: 10.1038/s41598-022-10929-y.
COVID-19 together with variants have caused an unprecedented amount of mental and economic turmoil with ever increasing fatality and no proven therapies in sight. The healthcare industry is racing to find a cure with multitude of clinical trials underway to access the efficacy of repurposed antivirals, however the much needed insights into the dynamics of pathogenesis of SARS-CoV-2 and corresponding pharmacology of antivirals are lacking. This paper introduces systematic pathological model learning of COVID-19 dynamics followed by derivative free optimization based multi objective drug rescheduling. The pathological model learnt from clinical data of severe COVID-19 patients treated with remdesivir could additionally predict immune T cells response and resulted in a dramatic reduction in remdesivir dose and schedule leading to lower toxicities, however maintaining a high virological efficacy.
COVID-19 及其变体导致了前所未有的精神和经济混乱,死亡率不断上升,目前尚无经过证实的治疗方法。医疗保健行业正在竞相寻找治疗方法,进行了大量的临床试验,以评估已上市抗病毒药物的疗效,但对抗 SARS-CoV-2 发病机制和相应抗病毒药理学的深入了解仍有所欠缺。本文提出了一种基于无导数优化的多目标药物重新调度的 COVID-19 动力学系统病理模型学习方法。从接受瑞德西韦治疗的重症 COVID-19 患者的临床数据中学习到的病理模型,还可以预测免疫 T 细胞的反应,从而显著减少瑞德西韦的剂量和使用时间,降低毒性,同时保持高病毒学疗效。