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

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 (AABs) targeting G-protein coupled receptors (GPCR-AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-AABs 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-AABs that acted as receptor agonists. Some of those GPCR-AABs 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-AAB detection). Other GPCR-AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-AABs identified in the blood of Long-COVID patients targeted the β-adrenoceptor (β-AAB), the α-adrenoceptor (α-AAB), the angiotensin II AT1-receptor (AT1-AAB), and the nociceptin-like opioid receptor (NOC-AAB). The negative chronotropic GPCR-AABs identified targeted the muscarinic M-receptor (M-AAB), the MAS-receptor (MAS-AAB), and the ETA-receptor (ETA-AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.