Longitudinal analysis of genomic mutations in SARS-CoV-2 isolates from persistent COVID-19 patient,iScience

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Longitudinal analysis of genomic mutations in SARS-CoV-2 isolates from persistent COVID-19 patient
iScience ( IF 4.6 ) Pub Date : 2024-03-29 , DOI: 10.1016/j.isci.2024.109597
Hiroki Futatsusako ₁ , Rina Hashimoto ₁ , Masaki Yamamoto ₂ , Jumpei Ito _{3,

4,

5} , Yasufumi Matsumura ₂ , Hajime Yoshifuji ₆ , Kotaro Shirakawa ₇ , Akifumi Takaori-Kondo ₇ , , Kei Sato _{3,

4,

5,

8,

9,

10,

11} , Miki Nagao ₂ , Kazuo Takayama _{1,

12}

Affiliation

Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 6068507, Japan.
Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
Graduate School of Medicine, The University of Tokyo, Tokyo 1138654, Japan.
International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
Department of Hematology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 2770882, Japan.
Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 8600811, Japan.
CREST, Japan Science and Technology Agency, Kawaguchi 3320012, Japan.
AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 1000004, Japan.

A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.5 for approximately 4 months to analyze its genome and evaluate drug resistance. Although the patient was administered the antiviral drug remdesivir (RDV), there were no acquired mutations in RDV binding site, and all isolates exhibited susceptibility to RDV. Notably, upon analyzing the S protein sequence of the day 119 isolate, we identified mutations acquired by mutant strains emerging from the BF.5 variant, suggesting that viral genome analysis in persistent COVID-19 patients may be useful in predicting viral evolution. These results suggest mutations in SARS-CoV-2 are acquired during long-term viral replication rather than in response to antiviral drugs.

中文翻译：

对持续性 COVID-19 患者分离出的 SARS-CoV-2 基因组突变进行纵向分析

2019 年冠状病毒病 (COVID-19) 持续传播的主要原因是严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 不断发生突变。然而，获得突变的机制尚不完全清楚。在这项研究中，我们从一名持续感染 Omicron BF.5 株约 4 个月的免疫功能低下患者中分离出 SARS-CoV-2，以分析其基因组并评估耐药性。尽管患者接受了抗病毒药物瑞德西韦（RDV），但RDV结合位点并未出现获得性突变，所有分离株均表现出对RDV的易感性。值得注意的是，在分析第 119 天分离株的 S 蛋白序列后，我们发现了 BF.5 变体中出现的突变株获得的突变，这表明持续性 COVID-19 患者的病毒基因组分析可能有助于预测病毒进化。这些结果表明，SARS-CoV-2 的突变是在长期病毒复制过程中获得的，而不是对抗病毒药物的反应。

更新日期：2024-03-29

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