Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus

作者：Wenda Guan, Rong Qu, Lihan Shen, Kailin Mai, Weiqi Pan, Zhengshi Lin, Liping Chen, Ji Dong, Jiawei Zhang, Pei Feng, Yunceng Weng, Minfei Yu, Peikun Guan, Jinchao Zhou, Chuanmeizi Tu, Xiao Y. Wu, Yang Wang, Chunguang Yang, Yun Ling, Sheng Le, Yangqing Zhan, Yimin Li, Xiaoqing Liu, Heyan Zou, Ziqi Huang, Hongxia Zhou, Qiubao Wu, Wenjie Zhang, Jiayang He, Teng Xu, Nanshan Zhong, Zifeng Yang · 发表于：Med · 年份：2023 · DOI：10.1016/j.medj.2023.11.001 · 被引用次数：24 · 研究领域：Influenza Virus Research Studies、Respiratory viral infections research、Immune Response and Inflammation

BACKGROUND: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. METHODS: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. FINDINGS: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. CONCLUSIONS: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatme...