Key result
Long COVID and spike-protein exposure are linked to elevated endothelin receptor type A autoantibodies.
Why the study?
Endothelial dysfunction mediated by elevated autoantibodies against vasoactive peptides after COVID-19 infection is proposed as a possible mechanism for orthostatic intolerance in long COVID patients.
Are circulating autoantibodies against vasoactive biomarkers elevated in long COVID patients with orthostatic intolerance compared to controls?
Case-Control (n=160)
No
Are circulating autoantibodies against vasoactive biomarkers elevated in long COVID patients with orthostatic intolerance compared to controls?
p-value: p=<0.0001
Elevated ETAR autoantibodies are present in individuals exposed to SARS-CoV-2 antigens (via infection or vaccination) and correlate with impaired daily activities in long COVID, though they do not specifically explain orthostatic intolerance.
ETAR autoantibodies may mark prior spike exposure in long COVID; leaves open their role in orthostatic intolerance.
Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item “Problems in performing usual activities”.
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Han et al. (2025) conducted a case-control in Long COVID (n=160). SARS-CoV-2 spike protein exposure (Long COVID, asymptomatic, or vaccinated) vs. Spike-naïve healthy controls was evaluated on Endothelin receptor type A (ETAR) autoantibody concentration (p=<0.0001). Endothelin receptor type A (ETAR) autoantibody concentrations were significantly elevated in long COVID patients and other spike-exposed groups compared to spike-naïve healthy controls (p<0.0001).
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