基于基因组分析确定的耐药突变治疗持续感染 SARS-CoV-2 的免疫功能低下个体的临床经验:一项描述性研究。
Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study.
发表日期:2023 Nov 09
作者:
Haruka Shimazu, Daiki Wada, Shuhei Maruyama, Akira Inoue, Masami Kashihara, Tomoyuki Yoshihara, Fukuki Saito, Kazuhisa Yoshiya, Yasushi Nakamori, Yasuyuki Kuwagata
来源:
MEDICINE & SCIENCE IN SPORTS & EXERCISE
摘要:
据报道,中和抗体药物并对抗 SARS-COV-2 的抗病毒药物的功效在体外会因病毒的基因突变而减弱。当B细胞免疫功能低下的患者感染SARS-COV-2时,感染时间可能会延长,并且在治疗过程中可能会出现基因突变。因此,对于持续感染COVID-19的难治性患者,进行基因组分析以获得耐药突变数据,作为确定哪些抗病毒药物和抗体疗法可能对其治疗有效的参考。这是一项没有对照的描述性分析。 2022 年 1 月至 2023 年 1 月期间,患者在关西医科大学综合医学中心被诊断为患有 COVID-19,并进行了检查和治疗。研究对象是 B 细胞免疫功能低下的患者,对这些患者进行了 SARS-CoV-2 的基因组分析。研究期间,有 984 名 COVID-19 患者在我们医院接受治疗。其中,17 例难治性病例接受了基因组分析。所有17名患者均患有恶性淋巴瘤或器官移植后等免疫缺陷相关因素。 11 名患者在我们医院开始了 COVID-19 的初步治疗,出现持续感染,并接受了基因组分析。六名最初在其他医院接受 COVID-19 治疗的患者后来持续感染,并被转移到我们医院。在 COVID-19 治疗之前,基因组分析显示 NSP5、NSP12 和 RBD 区域没有宿主内突变。在接受 COVID-19 治疗后,17 例病例中的 12 例(71%)发现了这些区域的突变。 16 名患者在隔离中幸存,但 1 名患者死于败血症。 在基因组分析中,发现 COVID-19 治疗后比 COVID-19 治疗前有更多的耐药突变。尽管无法证明基因组分析在临床应用中的有用性,但根据基因组分析表明的耐药性改变治疗药物可能会给免疫功能低下的 COVID-19 患者带来良好的结果。© 2023。作者)。
The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment.This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed.During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis.In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients.© 2023. The Author(s).