Abstract：
OBJECTIVE: Immunocompromised patients may experience prolonged shedding of influenza virus potentially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations.
METHODS: We investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies.
RESULTS: Successive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient\'s underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery.
CONCLUSIONS: These observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.
METHODS: We investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies.
RESULTS: Successive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient\'s underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery.
CONCLUSIONS: These observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.
摘要：
目的：。免疫功能低下的患者可能经历流感病毒的长时间脱落，可能导致严重的感染。应评估神经氨酸酶抑制剂单一疗法的替代方案，以完全抑制病毒复制并防止耐药突变。
方法：。我们调查了在不同治疗策略后，造血干细胞移植受者中持续性甲型流感和人类冠状病毒OC43（HCoV-OC43）共感染的临床和病毒学演变。
结果：。连续奥司他韦和扎那米韦单一疗法未能控制两种感染，阳性结果持续110天以上。由于神经氨酸酶突变（E119V和R292K），随后缺失（del245-248），这导致了高度耐药的奥司他韦菌株的出现。同时保持对扎那米韦的敏感性。宿主内病毒多样性数据表明，这些治疗方法影响了流感病毒的病毒多样性，但不是HCoV-OC43.考虑到患者的基本情况和长期病毒脱落对肺功能的影响，消灭流感病毒是必要的。结合扎那米韦和巴洛沙韦-marboxil的10天方案有效地控制了流感病毒的复制，并与HCoV-OC43的清除有关，最终导致全面的呼吸恢复。
结论：这些观察结果强调了进一步研究联合治疗作为免疫功能低下患者根除流感的主要方法的重要性。
方法：。我们调查了在不同治疗策略后，造血干细胞移植受者中持续性甲型流感和人类冠状病毒OC43（HCoV-OC43）共感染的临床和病毒学演变。
结果：。连续奥司他韦和扎那米韦单一疗法未能控制两种感染，阳性结果持续110天以上。由于神经氨酸酶突变（E119V和R292K），随后缺失（del245-248），这导致了高度耐药的奥司他韦菌株的出现。同时保持对扎那米韦的敏感性。宿主内病毒多样性数据表明，这些治疗方法影响了流感病毒的病毒多样性，但不是HCoV-OC43.考虑到患者的基本情况和长期病毒脱落对肺功能的影响，消灭流感病毒是必要的。结合扎那米韦和巴洛沙韦-marboxil的10天方案有效地控制了流感病毒的复制，并与HCoV-OC43的清除有关，最终导致全面的呼吸恢复。
结论：这些观察结果强调了进一步研究联合治疗作为免疫功能低下患者根除流感的主要方法的重要性。
