细胞因子水平作为重症 COVID-19 肺炎危重症患者死亡率的预测指标：哥伦比亚一项队列研究中的病例对照研究
Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia.
作者信息
Molina Francisco José, Botero Luz Elena, Isaza Juan Pablo, Cano Luz Elena, López Lucelly, Hoyos Lina Marcela, Correa Elizabeth, Torres Antoni
机构信息
Facultad de Medicina, Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia.
Intensive Care Unit, Clínica Universitaria Bolivariana, Universidad Pontificia Bolivariana, Medellín, Colombia.
出版信息
Front Med (Lausanne). 2022 Sep 29;9:1005636. doi: 10.3389/fmed.2022.1005636. eCollection 2022.
BACKGROUND
High levels of different cytokines have been associated in COVID-19 as predictors of mortality; however, not all studies have found this association and its role to cause multi-organ failure and death has not been fully defined. This study aimed to investigate the association of the levels of 10 cytokines with mortality in patients with COVID-19 admitted to the intensive care unit (ICU).
MATERIALS AND METHODS
This is a case-control study nested within a cohort of patients with COVID-19 who were on mechanical ventilation and were not hospitalized for more than 48 h across nine ICUs in Medellín, Colombia. Serum samples were collected upon admission to the ICU and 7 days later and used to measure cytokine levels.
RESULTS
Upon admission, no differences in mortality between the cytokine levels were observed when comparisons were made quantitatively. However, in the multivariate analysis, patients with median IL-1β levels <1.365 pg/ml showed an increase in mortality (OR = 3.1; 1.24<7.71; = 0.015). On day 7 in the ICU, IL-1β median levels were lower (0.34 vs. 2.41 pg/ml, = 0.042) and IL-10 higher (2.08 vs. 1.05 pg/ml, = 0.009) in patients who died. However, in the multivariate analysis, only IL-12p70 was associated with mortality (OR = 0.23; 0.07<0.73; = 0.012). The mean difference in the levels between day 1 and day 7 decreased in both IFN- (3.939 pg/ml, < 0.039) and in IL-18 (16.312 pg/ml, < 0.014) in the patients who died. A low IL-1β/IL-10 ratio was associated with mortality on both day 1 and day 7, while an IL-1β/IL-10 ratio below the cut-off on day 7 was associated with decreased survival. The lowest TNFα/IL-10 ratio was associated with mortality only on day 7.
CONCLUSION
At the time of admission, patients with median IL-1β levels lower than 1.365 pg/ml had increased mortality. An IL-1β/IL-10 ratio <2 at day 7 and IL-12p70 levels >1.666 pg/ml was associated with decreased survival.
背景
在新冠病毒疾病（COVID-19）中，高水平的不同细胞因子已被视为死亡率的预测指标；然而，并非所有研究都发现了这种关联，其导致多器官功能衰竭和死亡的作用尚未完全明确。本研究旨在调查入住重症监护病房（ICU）的COVID-19患者中10种细胞因子水平与死亡率之间的关联。
材料与方法
这是一项病例对照研究，嵌套于一组接受机械通气且在哥伦比亚麦德林市九个ICU住院时间不超过48小时的COVID-19患者队列中。在患者入住ICU时及7天后采集血清样本，用于测量细胞因子水平。
结果
入院时，定量比较细胞因子水平时未观察到死亡率的差异。然而，在多变量分析中，白细胞介素-（IL）-1β中位数水平<1.365 pg/ml的患者死亡率增加（比值比[OR]=3.1；1.24<7.71；P=0.015）。在ICU住院第7天，死亡患者的IL-1β中位数水平较低（0.34 vs. 2.41 pg/ml，P=0.042），而IL-10水平较高（2.08 vs. 1.05 pg/ml，P=0.009）。然而，在多变量分析中，只有IL-12p70与死亡率相关（OR=0.23；0.07<0.73；P=0.012）。死亡患者中，第1天和第7天细胞因子水平的平均差异在干扰素-γ（IFN-γ）（3.939 pg/ml，P<0.039）和IL-18（16.312 pg/ml，P<0.014）中均有所降低。低IL-1β/IL-10比值在第1天和第7天都与死亡率相关，而第7天IL-1β/IL-10比值低于临界值与生存率降低相关。最低的肿瘤坏死因子-α（TNFα）/IL-10比值仅在第7天与死亡率相关。
结论
入院时，IL-1β中位数水平低于1.365 pg/ml的患者死亡率增加。第7天IL-1β/IL-10比值<2且IL-12p70水平>1.666 pg/ml与生存率降低相关。
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