Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients.
Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients.
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DOI：
10.1038/s41420-021-00429-9
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发表时间：
2021-03-15
影响因子：
7
通讯作者：
Soundararajan V
中科院分区：
文献类型：
--
作者：
Awasthi S;Wagner T;Venkatakrishnan AJ;Puranik A;Hurchik M;Agarwal V;Conrad I;Kirkup C;Arunachalam R;O'Horo J;Kremers W;Kashyap R;Morice W 2nd;Halamka J;Williams AW;Faubion WA Jr;Badley AD;Gores GJ;Soundararajan V
重症COVID-19患者的重症监护室（ICU）入院率和死亡率是由“细胞因子风暴”和急性呼吸窘迫综合征（ARDS）驱动的。中期临床试验结果表明，皮质类固醇地塞米松在需要通气或吸氧的严重COVID-19患者中显示出更好的28天生存率。在这项研究中，16名患者中有10名（62.5%）在皮质类固醇给药后平均血浆IL-6值超过10 pg/mL，也有更差的结果（即，ICU停留>15天或死亡），而未接受皮质类固醇的41例患者中有8例（19.5%）（p值= 0.0024）。鉴于皮质类固醇后IL-6水平与COVID-19严重程度之间的这种潜在关联，我们假设糖皮质激素受体（GR或NR 3C 1）可能与控制细胞因子释放综合征（CRS）的特定细胞类型中的IL-6表达偶联。研究来自严重COVID-19患者BALF的单细胞RNA-seq数据和来自泛组织扫描的近200万个细胞显示，肺泡巨噬细胞，平滑肌细胞和内皮细胞共表达NR 3C 1和IL-6，激发了未来对NR 3C 1功能调节与IL-6水平之间联系的研究。
Intensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by “cytokine storms” and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.
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