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

Abstract

AbstractSARS‐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.