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
- The Second Affiliated Hospital of Chongqing Medical University,
Chongqing, China
- Ophthalmology department of The Second Affiliated Hospital of
Chongqing Medical University, Chongqing, China
- 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