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Unveiling the metabolic and coagulation disruptions in SARS-CoV-2-associated acute macular neuroretinopathy: A
Xiaojing Xiong1,2, Zheng Zheng1,2, Chunlin Liu1,2
1The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
Insights
SARS-CoV-2 infection is linked to acute macular neuroretinopathy (AMN). This study found altered urea cycle metabolism and coagulation abnormalities in AMN patients, developing a predictive model for this rare ocular condition.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Metabolomics
Background:
- SARS-CoV-2 infection is associated with an increased incidence of acute macular neuroretinopathy (AMN).
- The precise mechanisms linking SARS-CoV-2 to AMN remain unclear.
- Understanding these mechanisms is crucial for diagnosing and managing this ocular complication.
Purpose of the Study:
- To investigate the underlying metabolic and coagulation alterations in patients with AMN-SARS-CoV-2.
- To identify potential biomarkers for AMN associated with SARS-CoV-2 infection.
- To develop a predictive model for AMN-SARS-CoV-2.
Main Methods:
- A case-control study comparing 14 AMN-SARS-CoV-2 patients with 14 SARS-CoV-2-infected controls without AMN.
- Serum metabolomic profiling using ultra-high-performance liquid chromatography-online electrospray mass spectrometry.
- Analysis of coagulation parameters and urea cycle metabolites, including arginase 1 (AGR1) and nitric oxide synthase activity.
Main Results:
- Significant alterations in serum metabolites were identified in AMN-SARS-CoV-2 patients, with 76 upregulated and 42 downregulated metabolites.
- Arginine metabolism within the urea cycle was notably altered (ornithine, citrulline, l-proline, ADAM), correlating with coagulation abnormalities (platelet crit, fibrinogen degradation product, fibrinogen).
- Increased AGR1 activity and reduced nitric oxide synthase activity were observed; a predictive model integrating urea cycle metabolites and coagulation parameters achieved an AUC of 0.96.
Conclusions:
- Metabolic dysregulation, particularly in the urea cycle, and coagulation abnormalities are key features of AMN-SARS-CoV-2.
- Specific urea cycle metabolites and coagulation markers show promise as diagnostic biomarkers for AMN-SARS-CoV-2.
- The developed predictive model offers a robust tool for identifying individuals at risk of developing AMN in the context of SARS-CoV-2 infection.
