PDF(Pubmed)
Abstract：
Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapies have considerable clinical implications. We present a patient who independently acquired a T21I mutation in the 3CL protease after nirmatrelvir exposure. The T21I mutation in the 3CL protease is one of the most frequent mutations responsible for nirmatrelvir resistance. However, limited reports exist on actual cases of SARS-CoV-2 with T21I and other mutations in the 3CL protease. The patient, a 55 year-old male, had COVID-19 during chemotherapy for multiple myeloma. He was treated with nirmatrelvir early in the course of the disease but relapsed, and SARS-CoV-2 with a T21I mutation in the 3CL protease was detected in nasopharyngeal swab fluid. The patient had temporary respiratory failure but later recovered well. During treatment with remdesivir and dexamethasone, viruses with the T21I mutation in the 3CL protease showed a decreasing trend during disease progression while increasing during improvement. The impact of drug-resistant SARS-CoV-2 on the clinical course, including its severity, remains unknown. Our study is important for examining the clinical impact of nirmatrelvir resistance in COVID-19.
摘要：
尽管2019年冠状病毒病（COVID-19）大流行即将结束，它仍然对免疫受损者和其他潜在疾病构成威胁。特别是在持续性COVID-19的病例中，赋予对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疗法抗性的新突变具有相当大的临床意义。我们介绍了一名患者，该患者在nirmatrelvir暴露后独立获得了3CL蛋白酶中的T21I突变。3CL蛋白酶中的T21I突变是引起尼马特雷韦抗性的最常见突变之一。然而,关于SARS-CoV-2在3CL蛋白酶中具有T21I和其他突变的实际病例的报道有限。病人,一个55岁的男性,在多发性骨髓瘤化疗期间患有COVID-19。他在病程早期接受了尼马特雷韦治疗，但复发了，在鼻咽拭子液中检测到3CL蛋白酶中具有T21I突变的SARS-CoV-2。患者出现暂时性呼吸衰竭，但后来恢复良好。在治疗期间，用remdesivir和地塞米松，在3CL蛋白酶中具有T21I突变的病毒在疾病进展期间显示出减少的趋势,而在改善期间则显示出增加的趋势。耐药SARS-CoV-2对临床过程的影响，包括严重程度,仍然未知。我们的研究对于检查尼马特雷韦耐药对COVID-19的临床影响很重要。
