Autonomic dysfunction and vasoregulation in Long COVID-19 are linked to anti-GPCR autoantibodies
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Background
SARS-CoV-2-triggered autoantibodies (AAB) targeting G protein-coupled receptors (GPCRs) have been suggested to contribute to the post-acute sequelae of COVID-19 (Post-COVID-19 Syndrome, PCS).
Objective
To characterize AABs involved in autonomic dysfunction such as rhythm control and vasoregulation in patients with post-acute sequelae of COVID-19 and profile the peripheral B- and T-cell receptor (B/TCR) architecture to identify immunogenetic imprints of autoimmunity.
Methods
Anti-GPCR AABs were characterized in patients with post-acute sequelae of COVID-19 with known alteration in autonomic nervous system functions assessed by heart rate variability (HRV). Adaptive immune receptor repertoire sequencing (AIRR-seq) was used to profile peripheral BCR and TCR architecture.
COVID-19 patients with severe or moderate acute disease, after recovery, and pre-pandemic healthy individuals served as controls. Cardio- and vasoactive effects of AABs were analyzed using 24h and exercise test blood pressure measurements. The direct effect of AABs on electromechanical coupling was tested in human induced pluripotent stem cell cardiomyocytes.
Results
AABs including AGT1/2Rab, ADRB1/2ab, M1/3Rab, and CXCR3ab were associated with HRV alterations. Analysis of the broad BCR repertoire metrics revealed high similarity between PCS patients and healthy controls for clonality and diversity measures. The level of somatic hypermutation as proxy for antigen-experience was equal to healthy controls.
Elevated CXCR3ab levels were linked to higher 24h mean arterial pressure, while patients with elevated M1Rab and CXCR3ab levels showed higher blood pressure during stress tests. AABs had no effect on beat frequence and amplitude of cardiomyocyte contraction in vitro.
Conclusions
These findings suggest that AABs play a modulatory role in sympathetic nervous system-mediated regulation of cardiac rhythm and vascular function in PCS. AAB levels did not correlate with B- and T-cell receptor repertoire metrics or TRBV gene usage.
Web | DOI | PDF | Journal of Allergy and Clinical Immunology | Open Access
Schmitz, Boris; Garbsch, René; Schäfer, Hendrik; Bär, Christian; Chatterjee, Shambhabi; Riemekasten, Gabriela; Schulze-Forster, Kai; Heidecke, Harald; Schultheiß, Christoph; Binder, Mascha; Mooren, Frank C.
[Line breaks added]
Background
SARS-CoV-2-triggered autoantibodies (AAB) targeting G protein-coupled receptors (GPCRs) have been suggested to contribute to the post-acute sequelae of COVID-19 (Post-COVID-19 Syndrome, PCS).
Objective
To characterize AABs involved in autonomic dysfunction such as rhythm control and vasoregulation in patients with post-acute sequelae of COVID-19 and profile the peripheral B- and T-cell receptor (B/TCR) architecture to identify immunogenetic imprints of autoimmunity.
Methods
Anti-GPCR AABs were characterized in patients with post-acute sequelae of COVID-19 with known alteration in autonomic nervous system functions assessed by heart rate variability (HRV). Adaptive immune receptor repertoire sequencing (AIRR-seq) was used to profile peripheral BCR and TCR architecture.
COVID-19 patients with severe or moderate acute disease, after recovery, and pre-pandemic healthy individuals served as controls. Cardio- and vasoactive effects of AABs were analyzed using 24h and exercise test blood pressure measurements. The direct effect of AABs on electromechanical coupling was tested in human induced pluripotent stem cell cardiomyocytes.
Results
AABs including AGT1/2Rab, ADRB1/2ab, M1/3Rab, and CXCR3ab were associated with HRV alterations. Analysis of the broad BCR repertoire metrics revealed high similarity between PCS patients and healthy controls for clonality and diversity measures. The level of somatic hypermutation as proxy for antigen-experience was equal to healthy controls.
Elevated CXCR3ab levels were linked to higher 24h mean arterial pressure, while patients with elevated M1Rab and CXCR3ab levels showed higher blood pressure during stress tests. AABs had no effect on beat frequence and amplitude of cardiomyocyte contraction in vitro.
Conclusions
These findings suggest that AABs play a modulatory role in sympathetic nervous system-mediated regulation of cardiac rhythm and vascular function in PCS. AAB levels did not correlate with B- and T-cell receptor repertoire metrics or TRBV gene usage.
Web | DOI | PDF | Journal of Allergy and Clinical Immunology | Open Access
