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.

Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue

“…OCT-A is able to visualize retinal macular and peripapillary capillary plexi. [5,[29][30][31] It is easy to handle and measures non-invasively without any contact to the human eye. The technical basis is the recording of a real-time motion signal, based on temporal changes of intravascular moving red blood cells (RBC).…”

“…[6, [12][13][14] It is assumed that autoimmunphenomena [15] including the generation of functional active autoantibodies [5,16] are involved in the pathogenesis of PCS with potential different PCS subgroups. [5,6] Studies examined increased D-dimer levels up to 4-month post-acute infection in approximately 25% of patients. The mechanisms of these persistent procoagulant effects in PCS are not clarified at this point of time.…”

“…Persistent symptoms could be neurocognitive impairments (brain fog, loss of attention), autonomic symptoms (chest pain, palpitations, tachycardia), gastrointestinal issues, musculoskeletal problems (myalgia), smell and taste dysfunction, cough, headache, and hair loss. [5][6][7] Studies reported that PCS affects even people with moderate acute COVID-19 who didn't require hospital care during the acute stage. [5,8,9] The absolute number of patients with PCS goes along with the shape and amplitude of the pandemic curve showing the risk of PCS for individual health, healthcare system and economy.…”

“…[5][6][7] Studies reported that PCS affects even people with moderate acute COVID-19 who didn't require hospital care during the acute stage. [5,8,9] The absolute number of patients with PCS goes along with the shape and amplitude of the pandemic curve showing the risk of PCS for individual health, healthcare system and economy. [10] Studies revealed that more than half of the patients with COVID-19 infection reported PCS-symptoms.…”

“…Recent studies revealed viral persistence, enduring texture damage including endotheliopathy, impaired microvasculature, hypercoagulation, thrombosis, neutrophil extracellular traps (NETs), chronic immune dysregulation, dysregulation of the renin-angiotensinaldosterone-system (RAAS) and hyperinflammation/autoimmunity as possible pathomechanisms of PCS. [6, [12][13][14] It is assumed that autoimmunphenomena [15] including the generation of functional active autoantibodies [5,16] are involved in the pathogenesis of PCS with potential different PCS subgroups. [5,6] Studies examined increased D-dimer levels up to 4-month post-acute infection in approximately 25% of patients.…”