在 2019 冠状病毒病（COVID-19）中，以白细胞介素-10 升高为特征的抗炎细胞因子反应比促炎细胞因子反应更能预测严重疾病和不良结局。
The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).
机构信息
Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
出版信息
Clin Chem Lab Med. 2020 Nov 26;59(3):599-607. doi: 10.1515/cclm-2020-1284. Print 2021 Feb 23.
OBJECTIVES
Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.
METHODS
Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit.
RESULTS
A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8.
CONCLUSIONS
The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
目的
严重的 2019 年冠状病毒病（COVID-19）与免疫失调状态有关。虽然研究重点是过度炎症，但对代偿性抗炎反应的研究甚少。本研究旨在通过评估白细胞介素-10（IL-10）和 IL-10/淋巴细胞计数比值及其与结局的关系，来评估 COVID-19 的抗炎细胞因子反应。
方法
招募因实验室确诊的 COVID-19 而到急诊部（ED）就诊的成年患者。主要终点是指数 ED 就诊后 30 天内 COVID-19 的最大严重程度。
结果
共纳入 52 例 COVID-19 患者。疾病严重程度较高的患者（p<0.05）以及发生严重急性肾损伤（AKI）和新阳性细菌培养的患者（均 p≤0.01）的 IL-10 和 IL-10/淋巴细胞计数均显著升高。多变量分析显示，IL-10 和 IL-10/淋巴细胞计数各增加一个单位，COVID-19 严重程度的优势比分别增加 42%（p=0.031）和 32%（p=0.013）。当标准化到一个单位标准差的规模时，IL-10 的增加是最大 30 天严重程度和严重 AKI 的更强预测指标，而不是 IL-6 或 IL-8 的增加。
结论
COVID-19 的过度炎症反应伴随着同时发生的抗炎反应，这与不良结局相关，并且可能增加新阳性细菌培养的风险。ED 就诊时的 IL-10 和 IL-10/淋巴细胞计数是 COVID-19 严重程度的独立预测指标。此外，升高的 IL-10 与结局的相关性强于促炎的 IL-6 或 IL-8。COVID-19 中的抗炎反应需要进一步研究，以实现针对 SARS-CoV-2 的更精确免疫调节治疗。
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