Clinical, Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

BackgroundThe second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.MethodsFive patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.ResultsFour patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).ConclusionExpectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.

研究背景：人感染H7N9禽流感病毒的第二波疫情于2013年8月前扩散至中国广东省，目前该病毒已在该地区禽类群体中形成地方性流行。
研究方法：本研究对2013年8月至2014年2月期间本院收治的5例H7N9病毒感染患者进行了深入调研。采用定量聚合酶链反应（quantitative polymerase chain reaction, Q-PCR）检测呼吸道病毒载量，通过基于微球的流式细胞术（bead-based flow cytometry）测定细胞因子水平。
研究结果：5例患者中4例存活，1例死亡。不同临床标本的呼吸道病毒载量与血浆、支气管肺泡灌洗液（broncho-alveolar fluid, BALF）中的细胞因子水平、所采用的治疗方案及临床转归均存在相关性。对于奥司他韦（oseltamivir）治疗无应答的患者，静脉输注扎那米韦（zanamivir）作为挽救治疗方案的效果似乎优于帕拉米韦（peramivir）。与咽拭子标本相比，痰液或气管内抽吸物（endotracheal aspirates）标本中的病毒载量更高且持续时间更久。在血浆及支气管肺泡灌洗液标本中均可检测到促炎细胞因子IP-10、MCP-1、MIG、MIP-1α/β、IL-1β及IL-8的表达上调。血浆中的细胞因子水平与病毒载量均与疾病严重程度相关。5例患者中有3例（60%）检出1型单纯疱疹病毒（herpes simplex virus type 1, HSV-1）再激活。
研究结论：相较于咽拭子标本，留取痰液或气管内抽吸物标本更适用于H7N9病毒的检测与病情监测。疾病严重程度与呼吸道病毒载量及细胞因子血症的程度均存在相关性。1型单纯疱疹病毒的再激活可能会对临床转归产生影响。