Protease inhibitor plasma concentrations associate with COVID-19 infection.
Protease inhibitor plasma concentrations associate with COVID-19 infection.
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DOI：
10.1093/oxfimm/iqab014
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发表时间：
2021
影响因子：
--
通讯作者：
Thiel S
中科院分区：
文献类型：
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作者：
Medjeral-Thomas NR;Troldborg A;Hansen AG;Pihl R;Clarke CL;Peters JE;Thomas DC;Willicombe M;Palarasah Y;Botto M;Pickering MC;Thiel S
蛋白酶抑制剂影响一系列先天免疫和炎症途径。我们定量了2019冠状病毒病（COVID-19）慢性血液透析患者的关键抗炎蛋白酶抑制剂的血浆浓度。这些样本是在病程早期收集的，以确定血浆蛋白酶抑制剂水平是否与COVID-19的存在和严重程度相关。我们使用基于抗体的免疫测定法测量了来自27名COVID-19血液透析患者的100个系列样本中C1酯酶抑制剂、α 2-巨球蛋白、抗凝血酶和α间抑制剂重链4（ITIH 4）的血浆浓度。在两种测定中测试ITIH 4，一种测定测量完整的ITIH 4，另一种还检测任何片段化的ITIH 4（总ITIH 4）。对照组为32名无COVID-19的血液透析患者和32名健康对照。我们根据当前和未来的COVID-19严重程度以及C反应蛋白比较了蛋白酶抑制剂浓度。结果进行了调整，重复测量和多重比较。对所有可用样本的分析表明，与透析对照组相比，COVID-19患者的血浆C1酯酶抑制剂和α 2 M较低，总ITIH 4较高。在COVID-19诊断后采集的第一份样本中也观察到了这些差异，诊断拭子的中位数为4天。重度COVID-19患者的血浆ITIH 4水平高于非重度COVID-19患者。血清C反应蛋白与血浆抗凝血酶、完整ITIH 4和总ITIH 4水平呈正相关。总之，血浆蛋白酶抑制剂浓度在COVID-19中改变。
Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.