Istanbul Atlas University, Faculty of Medicine, Department of Medical Pharmacology, Istanbul, Turkey.
Istanbul Atlas University, Faculty of Medicine, Department of General Surgery, Istanbul, Turkey.
Int Immunopharmacol. 2022 Sep;110:108939. doi: 10.1016/j.intimp.2022.108939. Epub 2022 Jun 9.
The coronavirus disease-2019 (COVID-19) pandemic has caused important health, economic, social, and cultural problems worldwide. Recent findings demonstrate an excessive cytokine release during the disease development, especially in the seriously life-threatening form of COVID-19. Among other chemokines and cytokines that are released in high amounts at the infection site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), midkine (MK), which is a potent pro-inflammatory growth factor/ cytokine, can be also overexpressed and contribute to the pathophysiological process in patients infected with SARS-CoV-2.
Serum was collected from 87 intensive care unit (ICU) patients that are COVID-19 positive and 50 healthy volunteers in the control group with a negative PCR test and without disease symptoms. Circulating MK concentration was measured by enzyme-linked immunosorbent assay (ELISA).
COVID-19 patients had a significantly higher serum MK concentration compared to non-COVID-19 control subjects (1892.8 ± 1615.8 pg/mL versus 680.7 ± 907.6 pg/mL, respectively; P < 0.001). The cut-off MK concentration was 716.7 pg/ mL, with the sensitivity and specificity of 75.9 % and 76.0 %, respectively. The area under the receiver operating characteristic (ROC) curve of MK was = 0.827. Our findings showed that circulating MK levels are significantly increased in SARS-CoV-2 infected patients.
We suggest that MK is involved in the pathogenesis of COVID-19 and may be a part of hypercytokinaemia. Therefore, MK may serve as a supporting biomarker in the diagnosis of COVID-19, and blocking MK actions or its targets may attenuate the inflammatory process and the severity of the disease.
2019 年冠状病毒病（COVID-19）大流行在全球范围内造成了重要的健康、经济、社会和文化问题。最近的研究结果表明，在疾病发展过程中会发生过度的细胞因子释放，特别是在 COVID-19 这种严重危及生命的形式中。在严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染部位大量释放的其他趋化因子和细胞因子中，中期因子（MK）是一种有效的促炎生长因子/细胞因子，也可能过表达，并有助于感染 SARS-CoV-2 的患者的病理生理过程。
从 87 名重症监护病房（ICU）COVID-19 阳性患者和 50 名 PCR 检测为阴性且无疾病症状的健康志愿者的对照组中采集血清。通过酶联免疫吸附试验（ELISA）测量循环 MK 浓度。
COVID-19 患者的血清 MK 浓度明显高于非 COVID-19 对照组（分别为 1892.8 ± 1615.8 pg/mL 和 680.7 ± 907.6 pg/mL，P < 0.001）。MK 的截断值为 716.7 pg/mL，其灵敏度和特异性分别为 75.9%和 76.0%。MK 的接收器操作特性（ROC）曲线下面积为 0.827。我们的研究结果表明，SARS-CoV-2 感染患者的循环 MK 水平显著升高。
我们认为 MK 参与了 COVID-19 的发病机制，可能是细胞因子血症的一部分。因此，MK 可能作为 COVID-19 诊断的支持性生物标志物，阻断 MK 作用或其靶点可能减轻炎症过程和疾病的严重程度。
