Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue

Abstract

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS  can affect patients with all COVID-19 disease severities. As previous studies  have revealed impaired blood flow as a provoking factor triggering PCS, it was  the aim of the present study to investigate the potential association between  self-reported chronic fatigue and retinal microcirculation in patients with PCS,  potentially indicating an objective biomarker. A prospective study was performed,  including 201 subjects: 173 patients with PCS and 28 controls. Retinal  microcirculation was visualized by OCT angiography (OCT-A) and quantified using  the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic  fatigue (CF) was assessed according to the variables of Bell’s score, age and  gender. VDs in the superficial vascular plexus (SVP), intermediate capillary  plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the  repetitions (12 times). Seropositivity for autoantibodies targeting G  protein-coupled receptors (GPCR-AAbs) was determined by an established  cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was  performed to detect possible differences in the least square means between the  different groups included in the analysis. An age effect in relation to VD was  observed between patients and controls (p < 0.0001). Gender analysis showed that  women with PCS showed lower VD levels in the SVP compared to male patients (p =  0.0015). The PCS patients showed significantly lower VDs in the ICP as compared  to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients,  the mixed model revealed a significant difference between those with chronic  fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI:  −4.5; −0.92)). The model included variables of age, gender and Bell’s score,  representing a subjective marker for CF. Consequently, retinal microcirculation  might serve as an objective biomarker in subjectively reported chronic fatigue in  patients with PCS.