Introduction
Over the past few years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a significant threat to global health systems, with over 700 million confirmed cases and a cumulative death toll exceeding 6 million. Patients afflicted with the coronavirus disease (COVID-19), resulting from SARS-CoV-2 infection, typically present a range of systemic symptoms, including fever, cough, fatigue, dyspnea, myalgia, headaches, diarrhea, anosmia, and ageusia[1]. It is now understood that COVID-19 predisposes to a prothrombotic state. In this regard, the virus directly impacts vascular endothelial cells, conducive to endothelial impairment and initiating a sequence of events activating coagulation pathways and platelets, thus fostering the formation of blood clots[2]. Meanwhile, the virus-induced inflammatory response contributes to a prothrombotic state[3]. Accordingly, COVID-19 has been linked to various thromboembolic complications[4], affecting diverse organ systems, including the lungs, heart, kidneys, and brain.
While ocular symptoms associated with SARS-CoV-2 infection are infrequent, the external eye is typically affected, with follicular or pseudomembranous conjunctivitis, keratoconjunctivitis, and episcleritis being most prevalent[5, 6]. It has been established that the retina, characterized by extensive vasculature, is susceptible to thromboembolic disorders. While less frequent, reports have emerged of posterior segment ocular manifestations among COVID-19 patients, primarily in the form of retinal vascular occlusion [7]. Acute macular neuroretinopathy (AMN), an infrequent condition initially documented by Bos and Deutman in 1975, has been associated with viral infections, intravenous injections, and preeclampsia[8]. Its characteristic features encompass fundus images that typically display dark red petaloid lesions surrounding the fovea, often accompanied by progressive, variable degrees of visual impairment and central visual field defects[9]. Ischemia of the deep capillary plexus (DCP) is reportedly the predominant cause of this condition[10]. An increasing body of evidence suggests that the emergence of the novel coronavirus has been paralleled by a surge in cases of AMN[11, 12]. Over the years, AMN has been primarily documented through case reports, emphasizing the analysis of optical coherence tomography (OCT) characteristics[13, 14].
Metabolism is a fundamental characteristic and essential life process, with metabolic dysregulation playing a pivotal role in the context of COVID-19. In recent years, metabolomics has attracted significant interest in mechanistic research and diagnostics pertaining to COVID-19 and related disorders[15, 16]. Indeed, multiple research teams have investigated the metabolite profiles associated with SARS-CoV-2 infections, revealing alterations in metabolites or metabolic pathways[17], including free fatty acids, kynurenine, sphingolipids, glucose, amino acids, tricarboxylic acid (TCA) cycle, and urea cycle. These alterations have been posited to contribute to changes in organ function and immune responses. However, no studies have hitherto examined the metabolomics of AMN-SARS-CoV-2 interactions. Our study addresses this gap by examining serum samples from 14 patients afflicted by this rare condition. Importantly, we sought to unravel the serum metabolomic profile of AMN-SARS-CoV-2, explore potential correlations between these metabolic shifts and coagulation parameters, identify potential biomarkers, and construct predictive models capable of differentiating AMN-SARS-CoV-2 from SARS-CoV-2 infection in the absence of AMN (SARS-CoV-2-no AMN). Indeed, by unraveling the metabolic alterations associated with AMN within the context of SARS-CoV-2 infection, this study has the potential to provide invaluable insights into the underlying mechanisms governing AMN development.