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.


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Different study with different result!

Anti-AT1R autoantibodies and prediction of the severity of Covid-19 - ScienceDirect
We analyzed the dosage of AT1Rab to test a possible correlation with the clinical situation of patients affected by SARS-CoV-2: the frequency of AT1Rab (>10 U/ml) in healthy population was 29.46% (38/129), which is higher than the frequency observed in people affected by SARS-CoV-2 who required hospitalization was 14.86% (4/34) (p = 0.019). These preliminary results highlight the association between the lack of AT1Rab and severity of infection that cause the hospitalization.

We then focused on only 40 patients with COVID-19 admitted in Intensive Care Unit for respiratory monitoring, and it was clear that all the ones who died had not the AT1Rab and the only 18% of survivors endowed with them, despite their severe conditions at hospitalization.

The results suggest that the presence of AT1R autoantibodies can possibly play a role in Sars-CoV-2 infection by decreasing the effect of AngII accumulation following the virus occupation of the ACE2 receptor. Since AT1Rab was present in the healthy control in absence of pathological manifestations, it could be explained as a consequence of a probable state of tolerance to the effect of the chronic stimulus of AT1Rab on its receptor. The increase of AngII due to the occupation of ACE2 by Sars-CoV-2 therefore finds, in subjects positive for anti.AT1R autoantibodies, an immune system “refractory” to acute activation, while in subjects without anti-AT1R autoantibodies can induce a violent cytokine storm.

Another hypothesis is that the presence of anti-AT1R autoantibodies may determines an increase in plasmatic AngII which makes itself available to bind to a second AT2R receptor.
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Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway - ScienceDirect

If anti ATR1 and ETAR antibodies play a role in ME/CFS and long covid, then strategy presented here may be beneficial

Hence, our data may provide a translational rationale for mTOR inhibitors in combination with receptor blockers in patients with non–HLA receptor recognizing antibodies.
mTOR inhibitor has already shown interest here

mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas | Phoenix Rising ME/CFS Forums