Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized COVID-19 patients
Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized COVID-19 patients
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DOI：
10.1016/j.yjmcc.2020.08.008
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发表时间：
2020-10-01
影响因子：
5
通讯作者：
Wang, Dao Wen
中科院分区：
文献类型：
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作者：
Li, Chenze;Jiang, Jiangang;Wang, Dao Wen
背景：已有报道称，在住院的新冠肺炎患者中，通过肌钙蛋白升高来衡量心脏损伤，预示着预后较差。然而，肌钙蛋白升高的动力学如何随着时间的推移与炎症和凝血生物标志物相互作用尚不清楚。我们评估了心脏损伤、炎症和凝血标志物的纵向随访与疾病严重程度和预后的关系。方法：我们回顾分析了2020年1月29日至4月1日在武汉同济医院就诊的2068例新冠肺炎患者，中国。我们将心脏损伤定义为超敏心肌肌钙蛋白I(hs-cTnI)高于参考上限的第99次。我们从纵向上探讨了非危重患者和危重患者hs-cTnI升高的动态变化及其与炎症(IL-6、IL-8、IL-10、IL-2受体、肿瘤坏死因子-α、C-反应蛋白)和凝血指标(d-二聚体、纤维蛋白原、国际标准化比率)的关系，并进一步将这些指标与生存者和死亡者联系起来。结果：中位年龄63岁(51~70岁)，其中51.4%为女性。与非危重患者(N=1,592，77.0%)、危重患者(定义为需要机械通气、休克或多器官衰竭)相比，危重患者(N=476，23.0%)入院时心脏损伤更频繁(30.3%比2.3%，p<；0.001)，住院期间死亡率增加(38.4%比0%，p<；0.001)。在危重病患者中，死亡者(N=183)在住院期间hs-cTnI水平持续升高，而存活者(N=293)在入院后第4天至第7天hs-cTnI水平下降。具体地说，心脏损伤是危重患者入院时、第4-7天和第8-14天死亡率的独立标志。Hs-cTnI与IL-6在入院时(r=0.59)、第4-7天(r=0.66)、第8-14天(r=0.61，均P<0.001)和d-二聚体(同一时间点r=0.54、0.65、0.61，均P<；0.001)呈正相关。Hs-cTnI与大多数其他炎症和凝血生物标志物之间具有相似的行为。结论：新冠肺炎危重患者常发生心脏损伤，入院后第3天hs-cTnI升高预示着预后不良。在住院期间的多个时间点，hs-cTnI与IL-6和d-二聚体呈一致的正相关可能提示非特异性细胞因子介导的心脏毒性。
Background: Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome.Methods: We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-alpha, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors.Results: Median age was 63 years (first to third quartile 51-70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p < 0.001), with increased mortality during hospitalization (38.4% vs. 0%, p < 0.001). Among critically ill patients, non-survivors (N = 183) had a continuous increase in hs-cTnI levels during hospitalization, while survivors (N = 293) showed a decrease in hs-cTnI level between day 4 and 7 after admission. Specifically, cardiac injury is an independent marker of mortality among critically ill patients at admission, day 4-7 and 8-14. Consistent positive correlations between hs-cTnI and interleukin (IL)-6 on admission (r = 0.59), day 4-7 (r = 0.66) and day 8-14 (r = 0.61; all p < 0.001) and d-dimer (at the same timepoints r = 0.54; 0.65; 0.61, all p < 0.001) were observed. A similar behavior was observed between hs-cTnI and most of other biomarkers of inflammation and coagulation.Conclusions: Cardiac injury commonly occurs in critically ill COVID-19 patients, with increased levels of hs-cTnI beyond day 3 since admission portending a poor prognosis. A consistent positive correlation of hs-cTnI with IL-6 and d-dimer at several timepoints along hospitalization could suggest nonspecific cytokine-mediated cardiotoxicity.