背景:SARS-CoV-2感染引起的ARDS中血浆生物标志物与临床结局的关联早于免疫调节剂的循证应用。
目的:哪些血浆生物标志物与常规用免疫调节剂治疗的SARS-CoV-2感染引起的ARDS患者的临床结局相关?
方法:我们在2020年12月至2021年3月入住ICU24小时内收集了因SARS-CoV-2感染引起的ARDS患者的血浆(N=69)。我们关联了16种炎症的总生物标志物(例如,IL-6),凝血(例如,D-二聚体),上皮损伤(例如,表面活性剂蛋白D),和内皮损伤(例如,血管生成素-2)的主要结局为住院死亡率和次要结局为通气率(基线和第3天)。
结果:30例患者(43.5%)在60天内死亡。所有患者都接受了皮质类固醇,6%的患者还接受了托珠单抗。与幸存者相比,非幸存者表现出更高的基线改良序贯器官衰竭评估评分(中位数,8.5[四分位数间距(IQR),7-9]vs7[IQR,5-8]);P=.004),较低的Pao2与Fio2比率(中位数,153[IQR,118-182]vs184[IQR,142-247];P=.04),和更高的通气比(中位数,2.0[IQR,1.9-2.3]vs1.5[IQR,1.4-1.9];P<.001)。炎症没有发现差异,凝血,或组间上皮生物标志物。非幸存者显示较高的中位数神经前体细胞表达,发育下调9(NEDD9)水平(中位数,8.4ng/mL[IQR,7.0-11.2ng/mL]vs6.9ng/mL[IQR,5.5-8.0ng/mL];P=.0025),血管性血友病因子域A2水平(8.7ng/mL[IQR,7.9-9.7ng/mL]对6.5ng/mL[IQR,5.7-8.7ng/mL];P=.007),血管生成素-2水平(9.0ng/mL[IQR,7.9-14.1ng/mL]vs7.0ng/mL[IQR,5.6-10.6ng/mL];P=0.01),和syndecan-1水平(15.9ng/mL[IQR,14.5-17.5ng/mL]vs12.6ng/mL[IQR,10.5-16.1ng/mL];P=0.01)。只有NEDD9水平达到调整后的显著性阈值(P<.003)。血浆NEDD9水平与60天死亡率相关(校正OR,9.7;95%CI,1.6-60.4;P=0.015)。Syndecan-1水平与基线(ρ=0.4;P=.001)和第3天通气比(ρ=0.5;P<.001)相关。
结论:炎症的生物标志物,凝血,在一组接受免疫调节剂统一治疗的ARDS患者中,上皮损伤与临床结局无关.然而,内皮生物标志物,包括血浆NEDD9,与60天死亡率相关.
BACKGROUND: The association of plasma biomarkers and clinical outcomes in ARDS resulting from SARS-CoV-2 infection predate the evidence-based use of immunomodulators.
OBJECTIVE: Which plasma biomarkers are associated with clinical outcomes in patients with ARDS resulting from SARS-CoV-2 infection treated routinely with immunomodulators?
METHODS: We collected plasma from patients with ARDS resulting from SARS-CoV-2 infection within 24 h of admission to the ICU between December 2020 and March 2021 (N = 69). We associated 16 total biomarkers of inflammation (eg, IL-6), coagulation (eg, D-dimer), epithelial injury (eg, surfactant protein D), and endothelial injury (eg, angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3).
RESULTS: Thirty patients (43.5%) died within 60 days. All patients received corticosteroids and 6% also received tocilizumab. Compared with survivors, nonsurvivors demonstrated a higher baseline modified Sequential Organ Failure Assessment score (median, 8.5 [interquartile range (IQR), 7-9] vs 7 [IQR, 5-8]); P = .004), lower Pao2 to Fio2 ratio (median, 153 [IQR, 118-182] vs 184 [IQR, 142-247]; P = .04), and higher ventilatory ratio (median, 2.0 [IQR, 1.9-2.3] vs 1.5 [IQR, 1.4-1.9]; P < .001). No difference was found in inflammatory, coagulation, or epithelial biomarkers between groups. Nonsurvivors showed higher median neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) levels (median, 8.4 ng/mL [IQR, 7.0-11.2 ng/mL] vs 6.9 ng/mL [IQR, 5.5-8.0 ng/mL]; P = .0025), von Willebrand factor domain A2 levels (8.7 ng/mL [IQR, 7.9-9.7 ng/mL] vs 6.5 ng/mL [IQR, 5.7-8.7 ng/mL]; P = .007), angiopoietin-2 levels (9.0 ng/mL [IQR, 7.9-14.1 ng/mL] vs 7.0 ng/mL [IQR, 5.6-10.6 ng/mL]; P = .01), and syndecan-1 levels (15.9 ng/mL [IQR, 14.5-17.5 ng/mL] vs 12.6 ng/mL [IQR, 10.5-16.1 ng/mL]; P = .01). Only NEDD9 level met the adjusted threshold for significance (P < .003). Plasma NEDD9 level was associated with 60-day mortality (adjusted OR, 9.7; 95% CI, 1.6-60.4; P = .015). Syndecan-1 level correlated with both baseline (ρ = 0.4; P = .001) and day 3 ventilatory ratio (ρ = 0.5; P < .001).
CONCLUSIONS: Biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes in a small cohort of patients with ARDS uniformly treated with immunomodulators. However, endothelial biomarkers, including plasma NEDD9, were associated with 60-day mortality.