Abstract：
SARS-CoV-2 infection has been associated with the increased incidence of acute macular neuroretinopathy (AMN), an infrequent ocular disorder. However, the precise mechanisms underpinning AMN in the context of SARS-CoV-2 infection (AMN-SARS-CoV-2) remain elusive. In this case-control study, 14 patients diagnosed with AMN-SARS-CoV-2 between 2022/12 and 2023/3 were enrolled and compared with 14 SARS-CoV-2-infected individuals without AMN, who served as controls (SARS-CoV-2-no AMN). Metabolomic profiling using ultrahigh-performance liquid chromatography-online electrospray mass spectrometry revealed significant alterations in serum metabolites in AMN-SARS-CoV-2 patients. Coagulation abnormalities were observed in AMN-SARS-CoV-2 patients, and their relationship with metabolic disorders was studied. Finally, a predictive model for AMN-SARS-CoV-2 was established. Seventy-six upregulated and 42 downregulated metabolites were identified in AMN-SARS-CoV-2 cases. Notably, arginine metabolism within the urea cycle was significantly altered, evidenced by variations in ornithine, citrulline, l-proline, and ADAM levels, correlating with abnormal coagulation markers like platelet crit, fibrinogen degradation product, and fibrinogen. Additionally, increased arginase 1 (AGR1) activity within the urea cycle and reduced nitric oxide synthase activity were observed in AMN-SARS-CoV-2. The integration of urea cycle metabolite levels with coagulation parameters yielded a robust discriminatory model for AMN-SARS-CoV-2, as evidenced by an area under the curve of 0.96. The findings of the present study enhance our comprehension of the underlying metabolic mechanisms associated with AMN-SARS-CoV-2 and offer potential diagnostic markers for this uncommon ocular disorder within the context of SARS-CoV-2 infection.
摘要：
SARS-CoV-2感染与急性黄斑神经视网膜病变（AMN）的发病率增加有关，罕见的眼部疾病。然而,在SARS-CoV-2感染（AMN-SARS-CoV-2）的背景下，支撑AMN的确切机制仍然难以捉摸。在这项病例对照研究中，纳入14例2022/12至2023/3之间诊断为AMN-SARS-CoV-2的患者，并与14例无AMN的SARS-CoV-2感染个体进行比较。谁作为对照（SARS-CoV-2-无AMN）。使用超高效液相色谱-在线电喷雾质谱进行的代谢组学分析显示，AMN-SARS-CoV-2患者的血清代谢物发生了显着变化。在AMN-SARS-CoV-2患者中观察到凝血异常，并研究了它们与代谢紊乱的关系。最后,建立了AMN-SARS-CoV-2的预测模型。在AMN-SARS-CoV-2病例中鉴定出76种上调和42种下调的代谢物。值得注意的是,尿素循环中的精氨酸代谢显著改变，鸟氨酸的变异证明了这一点,瓜氨酸,l-脯氨酸,和ADAM水平，与异常凝血标志物相关，如血小板crit，纤维蛋白原降解产物，和纤维蛋白原。此外,在AMN-SARS-CoV-2中观察到尿素循环中精氨酸酶1（AGR1）活性增加，一氧化氮合酶活性降低。尿素循环代谢物水平与凝血参数的积分产生了AMN-SARS-CoV-2的稳健判别模型，曲线下的面积为0.96。本研究的发现增强了我们对与AMN-SARS-CoV-2相关的潜在代谢机制的理解，并为SARS-CoV-2感染背景下这种罕见的眼部疾病提供了潜在的诊断标志物。
