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二肽基肽酶 3 和白细胞介素 6:COVID-19 诊断的潜在生物标志物,与肺部浸润有关。

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates.

机构信息

Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.

Department of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.

出版信息

Clin Exp Med. 2023 Dec;23(8):4919-4935. doi: 10.1007/s10238-023-01193-z. Epub 2023 Sep 21.

Abstract

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34-24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30-17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients.

摘要

冠状病毒 SARS-CoV-2 在全球范围内传播,导致一种称为 COVID-19 的呼吸道疾病。本研究的目的是研究二肽基肽酶 3(DPP3)和炎症生物标志物 IL-6、CRP 和白细胞是否与 COVID-19 相关,以及是否能够预测 COVID-19 患者与非 COVID-19 患者肺部浸润的严重程度。我们的前瞻性观察性研究纳入了 114 例 COVID-19 患者和 35 例非 SARS-CoV-2 呼吸道感染患者。在急诊科就诊时采集血样。102 例 COVID-19 患者和 28 例非 COVID-19 患者接受了 CT 成像(19 例门诊患者未接受 CT 成像)。如果有 CT 成像,则使用人工智能软件(CT 肺炎分析)来量化肺部浸润。根据浸润中位数(14.45%),将接受定量 CT 分析的患者分为两组(>中位数:55 例 COVID-19 和 9 例非 COVID-19,≤中位数:47 例 COVID-19 和 19 例非 COVID-19)。COVID-19 患者的 DPP3 明显升高(中位数 20.85ng/ml,95%CI 18.34-24.40ng/ml),而非 SARS-CoV-2 患者(中位数 13.80ng/ml,95%CI 11.30-17.65ng/ml;p<0.001,AUC=0.72),而 IL-6、CRP(均为 p<0.001)和白细胞(p<0.05,但 COVID-19 患者的水平较低)。关于二元逻辑回归分析,较高的 DPP3 浓度(OR=1.12,p<0.001)和较低的白细胞计数(OR=0.76,p<0.001)被确定为 SARS-CoV-2 感染的显著且独立的预测因子,而 IL-6 和 CRP(均为 p<0.001)则不然。与浸润中位数以下的患者相比,浸润中位数以上的 COVID-19 患者的 IL-6 明显升高(p<0.001,AUC=0.78)和非 COVID-19 患者(p<0.05,AUC=0.81)。CRP、DPP3 和白细胞在 COVID-19 患者中浸润中位数以上时增加(均为 p<0.05,AUC:CRP 0.82,DPP3 0.70,白细胞 0.67),而在浸润中位数以下时则减少,而非 COVID-19 患者(均为 p=0.001)。关于 COVID-19 的多元线性回归分析,CRP、IL-6 和白细胞(均为 p<0.05)与肺部浸润程度相关,而 DPP3 则无关(p=0.001)。DPP3 具有成为 COVID-19 特异性生物标志物的潜力。IL-6 可能作为一种预后标志物,用于评估呼吸道疾病患者肺部浸润的程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f837/10725357/81e3c9838e76/10238_2023_1193_Fig1_HTML.jpg

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