Li Wei, Yue Hong
Department of Biomedical Sciences, Joan C. Edwards School of Medicine of Marshall University, Huntington, WV, United States.
Front Med (Lausanne). 2021 Mar 22;8:653773. doi: 10.3389/fmed.2021.653773. eCollection 2021.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is a human respiratory disease. Hitherto, there is no effective treatment has been established. Patients with cardiovascular or diabetes comorbidities are a high-risk cohort. COVID-19 is accompanied by excessive systemic thrombotic events, but the mechanism is not yet known. Recent studies have indicated that thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and TYMP expression is increased in diabetic patients. By using data provided by the MGH (Massachusetts General Hospital) Emergency Department COVID-19 Cohort with Olink Proteomics, here we show that plasma TYMP level is correlated with the COVID-19 associated thrombotic event, inflammation, and organ damage, as evidenced by the positive correlations with plasma D-dimer, CRP (C reactive protein), and LDH (lactate dehydrogenase), as well as Interferons (IFN). Plasma TYMP is also positively correlated with COVID-19 patients who had respiratory symptoms. TYMP thus could be an acuity marker for COVID-19 diagnosis. Targeting TYMP with tipiracil, a selective TYMP inhibitor, which has been approved by the Food and Drug Administration for clinical use, could be a novel effective medicine for COVID-19.
2019冠状病毒病（COVID-19）由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，是一种人类呼吸道疾病。迄今为止，尚未确立有效的治疗方法。患有心血管疾病或糖尿病合并症的患者是高危人群。COVID-19伴有全身性血栓形成事件增多，但其机制尚不清楚。最近的研究表明，胸苷磷酸化酶（TYMP）在血小板活化、血栓形成中起重要作用，且糖尿病患者的TYMP表达增加。通过使用麻省总医院急诊科COVID-19队列与Olink蛋白质组学提供的数据，我们在此表明血浆TYMP水平与COVID-19相关的血栓形成事件、炎症和器官损伤相关，这可通过与血浆D-二聚体、C反应蛋白（CRP）、乳酸脱氢酶（LDH）以及干扰素（IFN）的正相关得以证明。血浆TYMP也与有呼吸道症状的COVID-19患者呈正相关。因此，TYMP可能是COVID-19诊断的一个严重程度标志物。使用替吉嘧啶（一种已获美国食品药品监督管理局批准用于临床的选择性TYMP抑制剂）靶向TYMP，可能成为治疗COVID-19的一种新型有效药物。
