Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Abstract

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and  therapeutic options are limited, as the pathomechanism of LC is elusive. As the  number of acute SARS-CoV-2 infections was and is large, LC will be a challenge  for the healthcare system. Previous studies revealed an impaired blood flow, the  formation of microclots, and autoimmune mechanisms as potential factors in this  complex interplay. Since functionally active autoantibodies against  G-protein-coupled receptors (GPCR-AAbs) were observed in patients after  SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs  with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by  an established cardiomyocyte bioassay in 42 patients with LC and 6 controls.  Retinal microcirculation was measured by OCT-angiography and quantified as macula  and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical  analysis yielded impaired VD in patients with LC compared to the controls, which  was accentuated in female persons. A significant decrease in macula and  peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor  angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The  present study might suggest that a seropositivity of GPCR-AAbs can be linked to  an impaired retinal capillary microcirculation, potentially mirroring the  systemic microcirculation with consecutive clinical symptoms.