ABSTRACT
Purpose : Long-COVID is assumed to have an autoimmune component. As a seropositivity of functional active autoantibodies against G-protein coupled receptors (GPCR-AAb) and an impaired retinal microcirculation, measured by OCT-angiography (OCT-A), was observed after COVID-19 infection, it was the aim of the present study to investigate the impact of GPCR-AAbs on retinal microcirculation in patients with LongCOVID. Methods : Seventy-six patients with Long-COVID (COVID-19 infection was confirmed by real time rt-PCR) were recruited. A seropositivity for GPCR-AAbs (Nociceptin-AAb, ß2-AAb, AT1-AAb, α1-AAb, MAS-AAb, M2-AAb, ETA-AAb) was analyzed by a specific rat cardiomyocyte bioassay in vitro. Macular (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) and peripapillary vessel density (VD) were measured by OCT-A (Spectralis II, Heidelberg, Germany). VD analysis was done by the Erlangen-Angio tool, including an APSifyed and Bruch's membrane opening (BMO) based analysis. Data were analyzed by mixed model (SAS version 9.4). Gender and age were set as covariates. The study was approved by the local ethics committee and was done in accordance with the tenets of the Declaration of Helsinki. Informed consent was achieved. Results : All patients with Long-COVID showed a seropositivity for GPCR-AAbs (100%). Female patients with Long-COVID showed lower macular and peripapillary VD compared to men. A significant effect of a seropositivity of AT1-AAb on age-corrected least squares means (LS-means) overall VD of DCP ([CI: 0,25;6.07], p=0.03). A seropositivity of α1-AAb showed a significant effect on age-corrected LS-mean overall VD of SVP ([CI: 0.07;2.69], p=0.04), of DCP ([CI: 0.36;3.25], p=0.01), and of PH ([CI: 1.17;5.59], p=0.01), respectively. A seropositivity of MAS-AAb yielded a significant effect on age-corrected LS-mean overall VD of DH (CI: 1.48;6.07, p=0.001). A seropositivity of ß2-AAb has a significant effect on agecorrected LS-mean overall VD of MH (CI: 0,02;1,94, p=0.04). For those effects, the covariate age was significant in the type III tests (p<0.05), thus analysis was done considering this age-effect. Conclusions : As autoimmune mechanisms were reported to be involved in the pathogenesis of Long-COVID, we postulate that functional active GPCR-AAb may have an impact on retinal microcirculation, being a propable correlate to systemic disease.