Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

• Published in: Journal of translational autoimmunity (Online) Vol. 4; p. 100100
• Main Authors: Wallukat, Gerd, Hohberger, Bettina, Wenzel, Katrin, Fürst, Julia, Schulze-Rothe, Sarah, Wallukat, Anne, Hönicke, Anne-Sophie, Müller, Johannes
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021; Elsevier
• Subjects: Autoantibody; Autoimmunity; COVID-19; Fatigue; Long-COVID; Post-covid-19 symptom; Research paper; Autoimmunity; NOC-fAAB; Post-covid-19 symptom; RAS; ETA-fAAB; Autoantibody; Long-COVID; Fatigue; SARS; β2-fAAB; CRPS; α1-fAAB; COVID-19; ACE2; MAS-fAAB; fAAB; AT1-fAAB; PoTS; GPCR; M2-fAAB; ETA-fAAB, Autoantibody targeting the endothelin receptor; PoTS, Postural orthostatic tachycardia syndrome; SARS, Severe acute respiratory syndrome; fAAB, Functional autoantibody; CRPS, Complex regional pain syndrome; ACE2, Angiotensin-converting enzyme 2 receptors; β2-fAAB, Autoantibody targeting the beta2-adrenoceptor; AT1-fAAB, Autoantibody targeting the angiotensin II AT1 receptor; M2-fAAB, Autoantibody targeting the muscarinic receptor; RAS, Renin angiotensin system; GPCR, G-protein coupled receptors; α1-fAAB, Autoantibody targeting the alpha1-adrenoceptor; MAS-fAAB, Autoantibody targeting the MAS receptor; NOC-fAAB, Functionally active autoantibody against the nociceptin receptor
• ISSN: 2589-9090; 2589-9090
• DOI: 10.1016/j.jtauto.2021.100100

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved. We, therefore investigated, whether GPCR-fAABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs that acted as receptor agonists. Some of those GPCR-fAABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-fAAB detection). Other GPCR-fAABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-fAABs identified in the blood of Long-COVID patients targeted the β2-adrenoceptor (β2-fAAB), the α1-adrenoceptor (α1-fAAB), the angiotensin II AT1-receptor (AT1-fAAB), and the nociceptin—like opioid receptor (NOC-fAAB). The negative chronotropic GPCR-fAABs identified targeted the muscarinic M2-receptor (M2-fAAB), the MAS-receptor (MAS-fAAB), and the ETA-receptor (ETA-fAAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies. •Sera from Long-COVID syndrome patients contained functionally active autoantibodies targeting G-protein coupled receptors.•Autoantibodies target β2- and α1-adrenoceptors, angiotensin II AT1-, muscarinic M2-, MAS-, nociceptin- and ETA-receptors.•Included syndromes were of neurological and cardiological origin, or a combination of both.•Such autoantibody patterns have previously been seen in COVID independent neurological deficits and cardiovascular disease.