G-PROTEIN-COUPLED RECEPTORS ANTIBODIES HAVE SUBSTANTIAL VASOREGULATIVE IMPLICATIONS IN LONG-COVID

Abstract

Objective: The Long-COVID syndrome is associated with the generation of autoantibodies to vasoregulative G-protein coupled receptors (GPCR), playing a potential key role in this disease. How far GPCR are related to vascular dysfunction in this context remains elusive. Design and method: We performed a cross-sectional study, enrolling 80 patients with Long-COVID. GPCR antibodies encompassed autoantibodies against Angiotensin-II-Receptor-1 (AGTR2), Beta-1 Adrenergic Receptor (ADRB1), Beta-2 Adrenergic Receptor (ADRB2), Endothelin Receptor (EDNRA), Muscarinergic Choline Receptor 3 (CHRM3), and Muscarinergic Choline Receptor 4 (CHRM4), all measured by ELISA. Vascular endothelial function was assessed by flow mediated dilation (FMD). We checked for vascular and systemic inflammation by measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) and high-sensitive C-reactive protein (hsCRP). We performed a non-invasive pulse wave analysis to investigate central aortic blood pressure as well as nailfold capillaroscopy. Results: 52 (65%) patients had positive antibody findings above previously established cut-off values. The median concentrations for AGTR2, ADRB1, ADRB2, EDNRA, CHRM3 and CHRM4 were 13.21 (interquartile range [IQR] 11.57-18.51) U/ml, 19.12 (IQR 16.03-27.54) U/ml, 14.18 (IQR 10.83-31.26) U/ml, 14.07 (IQR 11.30-25.19) U/ml, 13.73 (IQR 12.04-25.30) U/ml and 9.27 (IQR 7.15-13.02) U/ml, respectively. Correlation analysis showed strong and significant negative correlation of several GPCR antibodies with aortic systolic blood pressure (AGTR2 p=0.026, ADRB1 p=0.001, ADRB2 p=0.012) and aortic diastolic blood pressure (ADRB1 p=0.005, CHRM4 p=0.046). High EDNRA antibodies titers were associated with increasing FMD (p=0.038). ATGR2, ADRB2 and EDNRA had substantial negative correlation with inflammation as seen by lower hsCRP concentrations (p=0.025, p=0.001, p=0.017, respectively). None of the above mentioned antibodies were associated with Lp-PLA2 (p>0.05 each). None of the investigated subentities of nailfold capillaroscopy were significant for GPCR-antibodies. Conclusions: GPCR antibodies are present in Long-COVID and show various vascular implications in terms of vasorelaxation as seen in lower aortic systolic and diastolic blood pressure as well as in an amelioration of FMD. If this is the result of anti-inflammatory properties remains elusive.