Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.
Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.
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DOI：
10.1038/srep25359
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发表时间：
2016-05-05
影响因子：
4.6
通讯作者：
Kim YS
中科院分区：
文献类型：
--
作者：
Min CK;Cheon S;Ha NY;Sohn KM;Kim Y;Aigerim A;Shin HM;Choi JY;Inn KS;Kim JH;Moon JY;Choi MS;Cho NH;Kim YS
尽管中东呼吸综合征仍在持续传播，但对影响其严重程度和结果的因素的了解有限。我们分析了在一家医院治疗的14名MERS患者的临床数据和标本，这些患者总体上代表了广泛的疾病严重程度，从轻度发热性疾病到致命性肺炎，并根据严重程度和死亡率将患者分为四组。比较和动力学分析显示，高病毒载量、弱抗体反应和伴血小板减少的淋巴细胞减少与疾病死亡率相关，而淋巴细胞反应的持续和逐渐增加可能需要对MERS-CoV感染产生有效免疫。白细胞增多，主要是由于中性粒细胞和单核细胞的增加，通常在更严重和致命的病例中观察到。血液中IL-10、IL-15、TGF-β、EGF等细胞因子水平与疾病死亡率呈正相关或负相关。不同趋化因子的诱导与差异动力学在肺炎康复患者中比在轻度发热性疾病患者或死亡患者中更为突出。病毒学和免疫学反应与疾病严重程度和死亡率的相关性，以及它们对当前抗病毒治疗的反应，可能在中东呼吸综合征早期具有预后意义。
Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.