I. Department of Medicine, Gastroenterology and Hepatology, Sections of Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Leibniz Institute of Virology, Hamburg, Germany.
Cell Rep Med. 2022 Sep 20;3(9):100735. doi: 10.1016/j.xcrm.2022.100735. Epub 2022 Aug 16.
We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.
我们在此研究了抗病毒治疗（如瑞德西韦）对宿主内基因组多样性和 SARS-CoV2 变异株在感染时间延长的患者中的出现的影响。对 14 名患有严重疾病进展的 SARS-CoV2 感染患者的 112 份纵向呼吸道样本进行测序和变异分析显示，主要频率变异通常不会在长时间感染期间出现。然而，瑞德西韦治疗可以增加宿主内基因组多样性，并导致新型主要变异株的出现，这些变异株携带有固定突变。在一名接受 B 细胞耗竭治疗的患者中，这种情况尤为明显，该患者在接受瑞德西韦治疗后，RNA 依赖性 RNA 聚合酶基因迅速出现突变。鉴于目前针对患有严重 SARS-CoV2 疾病的住院患者的治疗指南，以及瑞德西韦用于预防治疗高风险发生严重疾病进展的非住院患者，瑞德西韦治疗相关的新型变异株的出现引起了极大的关注。
