covid and autoantibodies against Angiotensin II Receptor Type 1 and Endothelin A Receptor


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Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms
panelGerdWallukatabBettinaHohbergercKatrinWenzelbJuliaFürstdSarahSchulze-RothebAnneWallukatbAnne-SophieHönickebJohannesMüllerb rights and content


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.

13 May 2021 |
Antibodies Against Angiotensin II Receptor Type 1 and Endothelin A Receptor Are Associated With an Unfavorable COVID19 Disease Course
Jelle Miedema
Marco Schreurs
Simone van der Sar – van der Brugge
Marthe Paats1,
Sara Baart4,
Marleen Bakker1,
Rogier Hoek
Willem Arnout Dik
Henrik Endeman5,
Vincent Van Der Velden
Adriaan van Gammeren6,
Antonius Ermens6,
Joachim G. Aerts
1 and
Jan Von Der Thüsen

Background: Lung histopathology demonstrates vasculopathy in a subset of deceased COVID19 patients, which resembles histopathology observed in antibody-mediated lung transplant rejection.

Autoantibodies against angiotensin II type 1 receptor (AT1R) and Endothelin receptor Type A (ETAR) have been demonstrated in antibody-mediated rejection and may also be associated with severe COVID19 infection.

Objective To assess AT1R and ETAR auto-antibodies in COVID19 patients and controls, and explore their association with disease course.

Methods: 65 hospitalized patients with COVID19 infection were included. Clinical and laboratory findings were retrospectively assessed. Patients with unfavorable disease course, admitted at the intensive care unit and/or deceased during hospital admission (n=33) were compared to admitted COVID19 patients with favorable disease course (n=32). The presence of antinuclear antibodies (ANA) and auto-antibodies against AT1R or ETAR in peripheral blood were compared between COVID19 with unfavorable and favorable disease course and age matched controls (n=20).

The presence of ANA was not significantly different between COVID19 patients with unfavorable (n=7/33; 21%) and favorable disease course (n=6/32; 19%) (p= 0.804) and controls (n=3/20; 15%).

Auto-antibodies against AT1R were significantly increased in unfavorable disease course (median 14.59 U/mL, IQR 11.28 – 19.89) compared to favorable disease course (median 10.67 U/mL, IQR 8.55 – 13.0, p< 0.01).

ETAR antibody titers were also significantly increased in unfavorable disease course (median 7.21, IQR 5.0 – 10.45) as compared to favorable disease course (median 4.0, IQR 3.0 – 6.0, p <0.05).

Conclusion: Auto-antibodies against AT1R and ETAR are significantly increased in COVID19 patients with an unfavorable disease course.