International journal of molecular sciencesFeb 27, 2026

Autoantibodies Against Cell Signaling Receptors May Be Common in Long COVID

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Feb 28, 2026

Abstract

Fifteen participants were enrolled, with eleven classified as having severe Long COVID and higher fatigue assessment scores (33 vs. 12).

Long COVID patients exhibited a higher prevalence of autoantibodies targeting G protein-coupled receptors compared to asymptomatic post-COVID individuals.
Mean levels of these autoantibodies were 8.88 Units/mL in Long COVID patients versus 5.45 Units/mL in asymptomatic participants.
Morning cortisol levels were significantly lower in Long COVID patients, measuring 12.7 mg/dL compared to 17 mg/dL in asymptomatic individuals.
T-cell responses to SARS-CoV-2 Spike and Nucleocapsid proteins appeared to be weaker in Long COVID patients.
The findings point to an autoimmune signature in Long COVID that may correlate with the development of symptoms.

Simplified

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 (= 0.03), fewer vaccine doses (= 0.03), and higher FAS scores (33 vs. 12;= 0.001). Mean GPCR AAbs levels were higher in LC than in APC (8.88 vs. 5.45 Units/mL;= 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;= 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. p p p p p

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The authors declare no conflicts of interest.

PubMed

Autoantibodies Against Cell Signaling Receptors May Be Common in Long COVID

Abstract

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Funding

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Abstract

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