Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis.
Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis.
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DOI：
10.3389/fimmu.2021.798338
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发表时间：
2021
影响因子：
7.3
通讯作者：
Ogura H
中科院分区：
文献类型：
--
作者：
Ebihara T;Matsumoto H;Matsubara T;Togami Y;Nakao S;Matsuura H;Kojima T;Sugihara F;Okuzaki D;Hirata H;Yamamura H;Ogura H
2019冠状病毒病（COVID-19）是一种新型病毒性疾病。被称为“细胞因子风暴”的不受控制的炎症据报道有助于疾病的发病机制以及败血症。我们的目标是通过对1463种血浆蛋白进行蛋白质组学分析来鉴定与COVID-19发病机制相关的细胞因子，验证这些细胞因子，并将其与败血症进行比较。在306名COVID-19患者的衍生队列中，在第1、4和8天测量了1463种独特的血浆蛋白。与疾病的严重程度和预后相关的细胞因子。在重症监护室[ICU]治疗的62名COVID-19患者和38名脓毒症患者的验证队列中，在第1天（ICU入院当天）、第2-3天和第6-8天（最多：3个时间点/患者）测量了这些衍生的细胞因子。将衍生的细胞因子与健康对照以及COVID-19和脓毒症患者进行比较，并评估其与预后的相关性。仅对COVID-19的机械通气（MV）脱机时间进行了评估。在衍生队列中，IL-6、双调蛋白和生长分化因子（GDF）-15与疾病严重程度和预后相关。在验证队列中，IL-6和GDF-15在第1天在COVID-19和脓毒症中升高，脓毒症中这些细胞因子的水平高于COVID-19。IL-6和GDF-15与脓毒症预后相关。以时间作为依赖协变量的考克斯比例风险模型显示血浆GDF-15水平与脱离MV的时间之间存在显著关系（风险比，0.549 [95%置信水平，0.382-0.789]）。ICU入院时的GDF-15水平预测晚期恢复。蛋白质组学分析得出的GDF-15和IL-6与COVID-19的疾病严重程度相关。它们的值在脓毒症中高于COVID-19，并与脓毒症的预后相关。在ICU接受治疗的COVID-19患者中，GDF-15与脱离MV的时间相关，并且更好地预测了后期恢复。
Coronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called “cytokine storm” is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis. In a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19. IL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382–0.789]). The GDF-15 level at ICU admission predicted late recovery. GDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery.
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DOI：
10.1136/bmj.n1135
发表时间：
2021-05-24
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Bodilsen J;Nielsen PB;Søgaard M;Dalager-Pedersen M;Speiser LOZ;Yndigegn T;Nielsen H;Larsen TB;Skjøth F
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Skjøth F
影响因子：
28.3
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通讯作者：
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DOI：
10.1164/rccm.202005-1583oc
发表时间：
2020-09-15
影响因子：
24.7
作者：
McElvaney, Oliver J.;McEvoy, Natalie L.;McElvaney, Noel G.
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McElvaney, Noel G.
DOI：
10.1016/s2352-3026(21)00105-8
发表时间：
2021-07
期刊：
The Lancet. Haematology
影响因子：
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Leentjens J;van Haaps TF;Wessels PF;Schutgens REG;Middeldorp S
通讯作者：
Middeldorp S