SEVERITY OF NEUROLOGICAL LONG-COVID SYMPTOMS CORRELATES WITH INCREASED LEVEL OF AUTOANTIBODIES TARGETING VASOREGULATORY AND AUTONOMIC NERVOUS SYSTEM RECEPTORS

Abstract

Objective: The Long-COVID syndrome is characterized by a variety of physical, cognitive and psychological symptoms. Worldwide, at least 65 million people are thought to be affected, nevertheless there is still insufficient knowledge about the pathogenesis of long-COVID. Studies on the Long-COVID related myalgicencephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest autoimmune-related changes, for example the formation of autoantibodies against G protein-coupled receptors. Design and method: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). Autoantibodies towards the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA. Neurological disorders and fatigue were quantified by internationally standardized questionnaires including Chalder Fatigue Scale, Short-Form-36 Questionnaire and the CERAD Neurophysiological Assessment Battery. Results: The prevalence and concentrations of evaluated autoantibodies were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1∗10-9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R <= -0.26, p <= 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087). Conclusions: The present study shows that autoantibodies to GPCR are highly prevalent in patients with Long-COVID. These autoantibodies occur in healthy controls as well, but the prevalence is substantially lower. Concentrations of autoantibodies correlates to intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.