Characterization of the Inflammatory Response to Severe COVID-19 Illness
Characterization of the Inflammatory Response to Severe COVID-19 Illness
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DOI：
10.1164/rccm.202005-1583oc
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发表时间：
2020-09-15
影响因子：
24.7
通讯作者：
McElvaney, Noel G.
中科院分区：
文献类型：
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作者：
McElvaney, Oliver J.;McEvoy, Natalie L.;McElvaney, Noel G.
理由：冠状病毒疾病（COVID-19）是对健康的全球威胁。其炎症特征尚未完全了解。目的：确定COVID-19的细胞因子谱，并确定重症患者免疫代谢改变的证据。方法：IL-1 β、IL-6、IL-8、IL-10和sTNFR 1水平在健康志愿者、住院但病情稳定的COVID-19患者的血浆中评估了可溶性肿瘤坏死因子受体1（可溶性肿瘤坏死因子受体1）（COVID稳定患者）、需要ICU入院的COVID-19患者（COVIDICU患者）以及需要ICU支持的严重社区获得性肺炎患者（CAP（ICU）患者）。在来自严重COVID-19患者的循环中性粒细胞中测量免疫代谢标志物。还评估了AAT（α-1抗胰蛋白酶）对COVID-19的急性期反应。测量和主要结果：在COVID-19患者中，IL-1 β、IL-6、IL-8和sTNFR 1均升高。COVIDICU患者可以与COVID稳定患者明确区分，并且表现出比CAP（ICU）患者更高的IL-1 β、IL-6和sTNFR 1水平，但更低的IL-10水平。COVID-19中性粒细胞显示免疫代谢改变，胞浆PKM 2（丙酮酸激酶M2）、磷酸化PKM 2、HIF-1 α（缺氧诱导因子-1 α）和乳酸盐增加。在COVID-19中，AAT的产生和唾液酸化增加，但在严重疾病中，这种免疫应答被淹没，需要ICU入院的患者中IL-6：AAT比率明显较高（P < 0.0001）。在COVID-19重症患者中，IL-6：AAT升高预测ICU住院时间延长和死亡率，而IL-6：AAT改善与临床缓解相关（P <0. 0001）。结论：COVID-19细胞因子血症与其他类型肺炎不同，导致器官衰竭和ICU需求。中性粒细胞在严重COVID-19疾病中经历免疫代谢重编程。细胞因子比值可以预测这一人群的结局。
Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: Todefine the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1 beta, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community acquired pneumonia requiring ICU support (CAP(ICU) patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated. Measurements and Main Results: IL-1 beta, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1 beta, IL-6, and sTNFR1 but lower IL-10 than CAP(ICU) patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinaseM2), phosphorylated PKM2, HIF-1 alpha (hypoxia-inducible factor-1 alpha), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.