Mabrey F Linzee, Morrell Eric D, Bhatraju Pavan K, Sathe Neha A, Sakr Sana S, Sahi Sharon K, West T Eoin, Mikacenic Carmen, Wurfel Mark M
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.
Translational Research, Benaroya Research Institute, Seattle, WA.
Crit Care Explor. 2021 Dec 9;3(12):e0591. doi: 10.1097/CCE.0000000000000591. eCollection 2021 Dec.
In bacterial sepsis, CD14 and its N-terminal fragment (soluble CD14 subtype, "Presepsin") have been characterized as markers of innate immune responses and emerging evidence has linked both to coronavirus disease 2019 pathophysiology.
Our aim was to determine the relationship between the soluble form of CD14 and soluble CD14 subtype plasma levels, coronavirus disease 2019 status, and coronavirus disease 2019-related outcomes.
A prospective cohort study.
ICUs in three tertiary hospitals in Seattle, WA.
Two-hundred four critically ill patients under investigation for coronavirus disease 2019.
We measured plasma soluble CD14 and soluble CD14 subtype levels in samples collected upon admission. We tested for associations between biomarker levels and coronavirus disease 2019 status. We stratified by coronavirus disease 2019 status and tested for associations between biomarker levels and outcomes.
Among 204 patients, 102 patients had coronavirus disease 2019 and 102 patients did not. In both groups, the most common ICU admission diagnosis was respiratory failure or pneumonia and proportions receiving respiratory support at admission were similar. In regression analyses adjusting for age, sex, race/ethnicity, steroid therapy, comorbidities, and severity of illness, soluble CD14 subtype was 54% lower in coronavirus disease 2019 than noncoronavirus disease 2019 patients (fold difference, 0.46; 95% CI, 0.28-0.77; = 0.003). In contrast to soluble CD14 subtype, soluble CD14 levels did not differ between coronavirus disease 2019 and noncoronavirus disease 2019 patients. In both coronavirus disease 2019 and noncoronavirus disease 2019, in analyses adjusting for age, sex, race/ethnicity, steroid therapy, and comorbidities, higher soluble CD14 subtype levels were associated with death (coronavirus disease 2019: adjusted relative risk, 1.21; 95% CI, 1.06-1.39; = 0.006 and noncoronavirus disease 2019: adjusted relative risk, 1.19; 95% CI, 1.03-1.38; = 0.017), shock, and fewer ventilator-free days. In coronavirus disease 2019 only, an increase in soluble CD14 subtype was associated with severe acute kidney injury (adjusted relative risk, 1.23; 95% CI, 1.05-1.44; = 0.013).
Higher plasma soluble CD14 subtype is associated with worse clinical outcomes in critically ill patients irrespective of coronavirus disease 2019 status though soluble CD14 subtype levels were lower in coronavirus disease 2019 patients than noncoronavirus disease 2019 patients. Soluble CD14 subtype levels may have prognostic utility in coronavirus disease 2019.
在细菌性败血症中，CD14及其N端片段（可溶性CD14亚型，“可溶性髓系细胞触发受体-1”）已被确定为先天性免疫反应的标志物，并且越来越多的证据表明二者均与2019冠状病毒病的病理生理学相关。
我们的目的是确定可溶性CD14和可溶性CD14亚型的血浆水平、2019冠状病毒病状态以及2019冠状病毒病相关结局之间的关系。
一项前瞻性队列研究。
华盛顿州西雅图市三家三级医院的重症监护病房。
204名因2019冠状病毒病接受调查的重症患者。
我们在入院时采集的样本中测量了血浆可溶性CD14和可溶性CD14亚型水平。我们检测了生物标志物水平与2019冠状病毒病状态之间的关联。我们根据2019冠状病毒病状态进行分层，并检测了生物标志物水平与结局之间的关联。
在204名患者中，102名患有2019冠状病毒病，102名未患。在两组中，最常见的重症监护病房入院诊断是呼吸衰竭或肺炎，入院时接受呼吸支持的比例相似。在对年龄、性别、种族/民族、类固醇治疗、合并症和疾病严重程度进行校正的回归分析中，2019冠状病毒病患者的可溶性CD14亚型比未患2019冠状病毒病的患者低54%（倍数差异，0.46；95%CI，0.28 - 0.77；P = 0.003）。与可溶性CD14亚型不同，2019冠状病毒病患者和未患2019冠状病毒病的患者之间可溶性CD14水平没有差异。在2019冠状病毒病患者和未患2019冠状病毒病的患者中，在对年龄、性别、种族/民族、类固醇治疗和合并症进行校正的分析中，较高的可溶性CD14亚型水平与死亡相关（2019冠状病毒病：校正相对风险，1.21；95%CI，1.06 - 1.39；P = 0.006；未患2019冠状病毒病：校正相对风险，1.19；95%CI，1.03 - 1.38；P = 0.017）、休克以及无呼吸机天数减少相关。仅在2019冠状病毒病患者中，可溶性CD14亚型升高与严重急性肾损伤相关（校正相对风险，1.23；95%CI，1.05 - 1.44；P = 0.013）。
无论是否患有2019冠状病毒病，较高的血浆可溶性CD14亚型与重症患者较差的临床结局相关，尽管2019冠状病毒病患者的可溶性CD14亚型水平低于未患2019冠状病毒病的患者。可溶性CD14亚型水平可能对2019冠状病毒病具有预后价值。
