Unveiling the metabolic and coagulation disruptions in SARS-CoV-2-associated acute macular neuroretinopathy: A case-control study

作者全名：Xiong, Xiaojing; Zheng, Zheng; Liu, Chunlin; Wang, Xinyu; Luo, Shuai; Xie, Qinqin; Liu, Yang; Chen, Qingwei; Zheng, Minming

作者地址：[Xiong, Xiaojing; Zheng, Zheng; Liu, Chunlin; Wang, Xinyu; Luo, Shuai; Xie, Qinqin; Liu, Yang; Chen, Qingwei; Zheng, Minming] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China; [Xiong, Xiaojing; Zheng, Zheng; Liu, Chunlin; Wang, Xinyu; Luo, Shuai; Xie, Qinqin; Liu, Yang; Zheng, Minming] Chongqing Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Chongqing 400010, Peoples R China; [Chen, Qingwei] Chongqing Med Univ, Affiliated Hosp 2, Dept Gen Practice, Chongqing 400010, Peoples R China

通信作者：Zheng, MM (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Chongqing 400010, Peoples R China.; Chen, QW (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gen Practice, Chongqing 400010, Peoples R China.

来源：JOURNAL OF MEDICAL VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001241598300001

JCR分区：Q1

影响因子：6.8

年份：2024

卷号：96

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：acute macular neuroretinopathy; coagulation disorders; SARS-CoV-2; serum metabolome

摘要：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.

基金机构：Chongqing Natural Science Foundation; Chongqing Municipal Health Commission Medical Research Project [2024WSJK097]; Scientific Research Project of Chongqing Sports Bureau [D202124]; Science and Technology Project Affiliated with the Science Department of Yuzhong District of Chongqing City [20210134]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [202228]; [CSTB2023NSCQ-MSX0115]

基金资助正文：The authors thank all of the patients involved in the study and all of the frontline medical staff at the Second Affiliated Hospital of Chongqing Medical University. The authors also would like to thank the technical support of the Shanghai Biotree Biotech Co., Ltd. This study is supported by the Chongqing Natural Science Foundation (Grant No. CSTB2023NSCQ-MSX0115), Chongqing Municipal Health Commission Medical Research Project (Grant No. 2024WSJK097), the Scientific Research Project of Chongqing Sports Bureau (Grant No. D202124), the Science and Technology Project Affiliated with the Science Department of Yuzhong District of Chongqing City (Grant No. 20210134), and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (Grant No. 202228).