Intensive Care Unit, Department of Translational medicine and for Romagna, University of Ferrara, Azienda Ospedaliera Universitaria di Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy.
Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, FE, Italy.
Crit Care. 2021 Feb 19;25(1):74. doi: 10.1186/s13054-021-03499-4.
Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS.
This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS.
In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001).
COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
生物标志物可用于检测 ARDS 中内皮和/或肺泡上皮损伤的存在。血管生成素-2（Ang-2）、可溶性细胞间黏附分子-1（ICAM-1）、血管细胞黏附蛋白-1（VCAM-1）、P 选择素和 E 选择素是内皮损伤的生物标志物，而晚期糖基化终产物受体（RAGE）则反映了肺泡上皮损伤。本研究的目的是评估以下生物标志物的血浆浓度是否存在差异：1）在 COVID-19 相关 ARDS 的幸存者和非幸存者之间，2）在 COVID-19 相关 ARDS 和经典 ARDS 之间。
这项前瞻性研究在费拉拉大学医院的两个 COVID-19 专用重症监护病房（ICU）和一个非 COVID-19 ICU 进行。招募了 31 名患有 COVID-19 ARDS 的机械通气患者和 11 名患有经典 ARDS 的患者。在三个时间点使用基于珠的多重免疫测定法测定 Ang-2、ICAM-1、VCAM-1、P-选择素、E-选择素和 RAGE：纳入研究时（T1）、第 7 ± 2 天（T2）和第 14 ± 2 天（T3）。主要结局是评估幸存者和非幸存者的生物标志物水平的血浆趋势。次要结局是评估幸存者和非幸存者之间呼吸力学变量和气体交换的差异。此外，我们比较了 COVID-19 相关 ARDS 和经典 ARDS 患者 T1 时生物标志物的血浆水平。
在 COVID-19 相关 ARDS 中，非幸存者的 Ang-2 和 ICAM-1 的血浆水平在 T1 时明显高于幸存者（p=0.04 和 p=0.03），而 P-选择素、E-选择素和 RAGE 的水平则没有差异。T1 时的 Ang-2 和 ICAM-1 是死亡率的预测因子（AUROC 分别为 0.650 和 0.717）。T1 时，RAGE 和 P-选择素水平在经典 ARDS 中高于 COVID-19 相关 ARDS。经典 ARDS 中 Ang-2、ICAM-1 和 E-选择素的水平低于 COVID-19 相关 ARDS（均 p<0.001）。
COVID-19 ARDS 的特点是早期的肺内皮损伤，通过 Ang-2 和 ICAM-1 检测到。COVID-19 ARDS 和经典 ARDS 表现出不同的生物标志物表达，提示不同的病理途径。试验注册 NCT04343053，登记日期：2020 年 4 月 13 日。
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