Unveiling the Metabolic and Coagulation Disruptions in SARS-CoV-2-Associated Acute Macular Neuroretinopathy: A Case-control Study
Xiaojing Xiong1,2, Zheng Zheng1,2, Chunlin Liu1,2, Xinyu Wang1,2, Shuai Luo1,2, Qinqin Xie1,2, Yang Liu1,2 , Qingwei Chen1,3, Minming Zheng1,2*
Xiaojing Xiong: 361335881@qq.com
Zheng Zheng: 1635193841@qq.com
Chunlin Liu: 570037067@qq.com
Xinyu Wang: 272884693@qq.com
Shuai Luo: 547604791@qq.com
Qinqin Xie: 1044898966@qq.com
Yang Liu: 1490532071@qq.com
Qingwei Chen: chenqwcq@163.com
Minming Zheng:304239@hospital.cqmu.edu.cn
corresponding author:Minming Zheng,Department of Ophthalmology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Email:304239@hospital.cqmu.edu.cn
  1. The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  2. Ophthalmology department of The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  3. General Practice Department of The Second Affiliated Hospital Of Chongqing Medical University, Chongqing, China
ABSTRACT
Background: 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.
Methods: In this case-control study 14 patients diagnosed with AMN-SARS-CoV-2 between 2022/12 and 2023/3 were enrolled in this study. 14 SARS-CoV-2-infected individuals without AMN (SARS-CoV-2-no AMN) as control. 14 AMN-SARS-CoV-2 patients were compared with 14 SARS-CoV-2-no AMN. Metabolomic profiling using Ultra-High-Performance Liquid Chromatography-Online Electrospray Mass Spectrometry (UHPLC-OE-MS) revealed significant alterations in serum metabolites in AMN-SARS-CoV-2 patients. Abnormal blood clotting was observed in AMN-SARS-CoV-2 patients, and its relationship with metabolic disorders was studied. Finally, a predictive model for AMN-SARS-CoV-2 was established.
Results: 76 upregulated and 42 downregulated metabolites were discovered in AMN-SARS-CoV-2. Notably, arginine metabolism within the urea cycle showed substantial changes, evidenced by variations in ornithine, citrulline, L-proline, and ADAM levels, correlating with abnormal coagulation markers like platelet crit (PCT), fibrinogen degradation products (FDP), and fibrinogen (Fbg). Additionally, increased arginase 1 (AGR1) activity within the urea cycle and reduced nitric oxide synthase (NOS) activity were observed in AMN-SARS-CoV-2. Combining these urea cycle metabolites with coagulation parameters effectively distinguished AMN-SARS-CoV-2 from SARS-CoV-2-no AMN, with an area under the curve (AUC) value of 0.96.
Conclusion: 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.
Keywords: SARS-CoV-2, Acute macular neuroretinopathy, Serum metabolome, Coagulation disruptions