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Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers
medRxiv - Cardiovascular Medicine Pub Date : 2021-03-05 , DOI: 10.1101/2021.03.03.21252841
Annika Lundström , Louise Ziegler , Sebastian Havervall , Ann-Sofie Rudberg , Fien von Meijenfeldt , Ton Lisman , Nigel Mackman , Per Sandén , Charlotte Thålin

Rationale: Angiotensin-converting enzyme 2 (ACE2) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) is unknown. Objective: To measure circulating ACE2 and ACE levels in COVID-19 patients and investigate associations with risk factors, outcome and inflammatory markers. Methods and results: Soluble ACE2 (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand factor (VWF), factor VIII (fVIII), D-dimer, interleukin 6 (IL-6), tumor necrosis factor α and plasminogen activator inhibitor 1 (PAI-1) had previously been determined. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19. sACE2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes and patients on RAS-inhibition. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 correlated with VWF, fVIII and D-dimer, while sACE correlated with IL-6, TNFα and PAI-1. Conclusions: sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed distinctly in their correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

中文翻译:

可溶性血管紧张素转换酶2在COVID-19中短暂升高,并与特定的炎症和内皮标记物相关

理由:血管紧张素转换酶2(ACE2)是严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)的主要进入受体,但SARS-CoV-2与ACE2的相互作用如何影响肾素-血管紧张素系统(RAS)。冠状病毒病2019(COVID-19)不详。目的:测量COVID-19患者循环中的ACE2和ACE水平,并探讨其与危险因素,预后和炎症标志物的关系。方法和结果:通过ELISA测定了114例经医院治疗的COVID-19患者和10例健康对照者的血浆样品中的可溶性ACE2(sACE2)和sACE浓度。58/114名患者在四个月后获得了随访样本。冯·威勒布兰德因子(VWF),因子VIII(fVIII),D-二聚体,白介素6(IL-6),先前已经确定了肿瘤坏死因子α和纤溶酶原激活物抑制剂1(PAI-1)。在COVID-19患者中,sACE2的水平高于健康对照组,中位数为5.0(四分位间距2.8-11.8)ng / ml,而中位值为1.4(1.1-1.6)ng / ml,p <0.0001。男性中sACE2高于女性,但不受严重COVID-19的其他危险因素影响。随访时,sACE2降至2.3(1.6-3.9)ng / ml,p <0.0001,但仍高于健康对照组,p = 0.012。对于糖尿病患者和具有RAS抑制作用的患者,随着年龄,BMI,合并症总数的增加,随访的sACE2水平较高。与随访时相比,COVID-19期间sACE略低,分别为57(45-70)ng / ml和72(52-87)ng / ml,p = 0.008。sACE2和sACE的水平没有差异,这取决于生存率或疾病的严重程度(护理水平,呼吸支持)。COVID-19期间sACE2与VWF,fVIII和D-二聚体相关,而sACE与IL-6,TNFα和PAI-1相关。结论:sACE2在COVID-19中瞬时升高,可能是由于感染细胞的脱落增加所致。sACE2和sACE在COVID-19期间与炎症和内皮功能障碍的标志物之间的相关性显着不同,表明从不同的细胞类型和/或血管床释放。
更新日期:2021-03-05
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