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.