# Prevalence of Circulating Autoantibodies Against G-Protein-Coupled Receptors as Potential Biomarkers for Long COVID: Preliminary Investigations

## TL;DR

This study explores autoantibodies targeting G-protein-coupled receptors in Long COVID patients as potential biomarkers and treatment targets.

## Contribution

The study identifies a potential autoimmune signature in Long COVID through elevated GPCR autoantibodies.

## Key findings

- LC patients had higher GPCR autoantibody levels compared to asymptomatic post-COVID individuals.
- LC patients showed lower morning cortisol levels and weaker T-cell responses.
- Findings suggest GPCR autoantibodies could guide diagnosis and treatment for some Long COVID patients.

## Abstract

This prospective, single-center, case-control study investigated circulating autoantibodies (AAbs) targeting G protein-coupled receptors (GPCRs) in Long COVID (LC) patients to identify potential diagnostic biomarkers and therapeutic targets. Fifteen participants were enrolled at the LC clinic in Rome: eleven with severe LC—defined as >4 persistent symptoms (fatigue, cognitive impairment, poor exercise tolerance, dyspnea, arthralgia, or dysautonomic manifestations) >3 months post-infection—and four asymptomatic post-COVID (APC) individuals. Fatigue was assessed using the Fatigue Assessment Scale (FAS ≥ 22; severe ≥ 35). Auto-Abs against AT1R, endothelin receptor A, adrenergic (α1, α2, β1, β2), and muscarinic (M1–M5) receptors were quantified, along with blood cortisol and ACTH levels. SARS-CoV-2-specific T-cell responses to Spike and Nucleocapsid proteins were evaluated by ELISpot assay. In our small cohort, LC patients were younger, had fewer comorbidities (p = 0.03), fewer vaccine doses (p = 0.03), and higher FAS scores (33 vs. 12; p = 0.001). Mean GPCR AAbs levels were higher in LC than in APC (8.88 vs. 5.45 Units/mL; p = 0.17), indicating a coherent autoimmune signature in LC that correlates with symptom development. Morning cortisol was lower in LC (12.7 vs. 17 mg/dL; p = 0.01), and T-cell responses tended to be weaker. These findings suggest GPCR AAbs may serve as biomarkers and therapeutic targets for a subset of patients, guiding diagnosis and treatments with IV immunoglobulin or immunoadsorption.