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Patients infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) can experience life-threatening respiratory distress, blood pressure dysregulation and thrombosis. This is thought to be associated with an impaired activity of angiotensin- converting enzyme-2 (ACE-2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized COVID-19 patients developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or RBD, to which they can cross- bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.
Competing Interest Statement
P.S.B., J.A.H. and M.A.S. are named as inventors on US Provisional Patent 63/123,199, filed December 9, 2020, relating to measurement of anti-AngII in immune response. The University of Chicago has filed a patent application relating to anti-SARS-CoV-2 antibodies generated by P.C.W., H.L.D., and C.T.S. as co-inventors.
This study was funded by the University of Chicago, through the Chicago Immunoengineering Innovation Center, the Chicago Biomedical Consortium and the University of Chicago Big Ideas Generator for COVID research. S.R.J. was supported by the T32 CA009566.
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The IRB of the University of Chicago, Department of Medicine gave ethical approval for this work.
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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv