The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018–2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018–19 influenza vaccine virus. Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.

中文翻译：

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从大韩民国免疫受损患者中分离到耐神经氨酸酶抑制剂的流感病毒的特征。

抗流感药物耐药的流感病毒的出现对全球公共卫生构成威胁。韩国疾病预防控制中心运营韩国流感和呼吸道病毒监测系统（KINRESS），以监测流感和严重急性呼吸道感染（SARI）的流行病，以识别影响耐药性，发病机制和传播的突变流感病毒。口咽拭子样本是在2018-2019年度从KINRESS和SARI收集的。标本在接种的MDCK细胞上使用实时RT-PCR确认了流感病毒。分析流感病毒的HA和NA序列的系统发育和突变。利用神经氨酸酶抑制和血凝抑制测定来表征分离物。在患有急性血液系统癌症的患者中检测到两个在神经氨酸酶序列中具有H275Y取代的A（H1N1）pdm09分离株。尽管存在奥司他韦和帕拉米韦治疗，但他们的呼吸道症状长期存在，病毒仍存在于呼吸道中。通过神经氨酸酶抑制试验，发现两种病毒均对奥司他韦和帕拉米韦具有抗性，但对扎那米韦不具抗性。尽管血凝素和神经氨酸酶的系统发育分析表明2个A（H1N1）pdm09分离株不相同，但其抗原性与2018-19流感疫苗病毒相似。我们的数据表明，在综合医院中监测流感感染的免疫功能低下的患者，可以及早发现新兴的抗神经氨酸酶抑制剂的病毒，并在前哨诊所对流感样疾病的患者进行持续的实验室监测，以监测此类新变异的传播。最后，病毒的鉴定可以为由耐药性流感病毒引起的未来流行和大流行的风险评估提供依据。