Severe COVID-19 induces autoantibodies against angiotensin II that correlate with blood pressure dysregulation and disease severity

• Published in: Science advances Vol. 8; no. 40; p. eabn3777
• Main Authors: Briquez, Priscilla S., Rouhani, Sherin J., Yu, Jovian, Pyzer, Athalia R., Trujillo, Jonathan, Dugan, Haley L., Stamper, Christopher T., Changrob, Siriruk, Sperling, Anne I., Wilson, Patrick C., Gajewski, Thomas F., Hubbell, Jeffrey A., Swartz, Melody A.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 07.10.2022
• Subjects: Angiotensin II; Angiotensin-Converting Enzyme 2; Autoantibodies; Biomedicine and Life Sciences; Blood Pressure; Coronavirus; COVID-19; Epitopes - metabolism; Humans; Immunology; Life Sciences; Peptidyl-Dipeptidase A - metabolism; Protein Binding; SARS-CoV-2; SciAdv r-articles; Severity of Illness Index; Spike Glycoprotein, Coronavirus
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abn3777

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 (ACE2), 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 patients with COVID-19 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 receptor-binding domain (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. Anti-AngII autoantibodies may contribute to dysregulated blood pressure and poor oxygenation in hospitalized patients with COVID.