The role of angiotensin II and endothelin receptor antibodies in COVID-19

BACKGROUND: The infection caused by the coronavirus SARS-CoV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-CoV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19.METHODS: A total of patients with COVID-19 and controls (free of COVID-19) were included. Patients were divided into two groups: patients with severe disease (30 patients admitted at the intensive care), and patients with milder clinical presentation that remained in the general therapeutical department (N.=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID-19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analyzed.RESULTS: Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69-17.67, P=0.017) and the control group (median 6.79 U/mL, IQR 5.10-14.05, P<0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59-13.45, P=0.023) and to the control group (median 6.64, IQR 6.79-17.92, P<0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59-19.38); milder disease (median 8.64 U/mL, IQR 1.84-14.13, P=0.039); control group (median 4.28 U/mL, IQR 0.11-1.43, P<0.001). Both AT1R and ETAR correlated to IL-6 plasma levels.CONCLUSIONS: In conclusion, we established the presence of AT1R and ETAR autoantibodies in COVID19 patients. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.