Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection
Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection
复制标题
DOI：
10.1086/650581
复制
发表时间：
2010-03-15
影响因子：
11.8
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
--
作者：
To, Kelvin K. W.;Hung, Ivan F. N.;Yuen, Kwok-Yung
背景2009年H1N1流感病毒引起的感染范围从轻微的上呼吸道综合征到致命疾病。然而，比较不同临床严重程度的病毒学和免疫学特征的研究缺乏。我们对74例甲型H1N1流感感染患者进行了回顾性队列研究，其中包括23例发生急性呼吸窘迫综合征（ARDS）或死亡（ARDS死亡组），14例氧饱和度下降但未发生ARDS的患者（无ARDS生存组），以及37例轻度疾病但无氧饱和度下降的患者（轻度疾病组）。我们比较了他们的临床疾病模式、病毒载量和免疫学特征。重度疾病患者年龄较大，更可能肥胖或有基础疾病，并有下呼吸道症状，尤其是就诊时呼吸困难。ARDS死亡组鼻咽部病毒载量下降较慢，血浆促炎细胞因子和趋化因子水平较高，并且与无ARDS生存组或轻度疾病组相比，更容易发生细菌合并感染（30.4%）、心肌炎（21.7%）或病毒血症（13.0%）。尸检中发现了类似于致命性禽流感H5N1感染的反应性噬血细胞、血栓形成现象、淋巴萎缩、弥漫性肺泡损伤和多器官功能障碍。在严重病例中，病毒载量和免疫失调的控制较慢，这要求寻找更有效的抗病毒和免疫调节方案，以阻止导致ARDS和死亡的过度细胞因子活化。
Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking.Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile.Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations.Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.