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

ABSTRACT: 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.

SUBMITTER: Briquez PS

PROVIDER: S-EPMC9544317 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Briquez Priscilla S PS Rouhani Sherin J SJ Yu Jovian J Pyzer Athalia R AR Trujillo Jonathan J Dugan Haley L HL Stamper Christopher T CT Changrob Siriruk S Sperling Anne I AI Wilson Patrick C PC Gajewski Thomas F TF Hubbell Jeffrey A JA Swartz Melody A MA

Science advances 20221007 40

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 si ...[more]

PMID: 36206332

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Project description:BackgroundAngiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-and-effect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest.MethodsWe used molecular biology approaches, immunohistochemistry, and electron microscopy to examine the interdependence between the hypertensive and pro-inflammatory effects of Ang II. We examined the effect of blood pressure by administering a subpressive (200 ng/kg/min) or a pressive Ang II dose (1000 or 1900 ng/kg/min) with and without hydralazine (150 mg/L) for 1 week and used phenylephrine to increase blood pressure independently of the renin-angiotensin system.ResultsAng II increased ionized calcium-binding adaptor molecule 1 (Iba-1) levels (marker of microgliosis) in the whole brain and in the hippocampus in a dose-dependent manner. Pressive Ang II induced specific changes in microglial morphology, indicating differences in functional phenotype. An increase in hippocampal glial fibrillary acidic protein (GFAP) was seen in mice receiving pressive Ang II, while no induction of cerebral gliosis was observed after 7 days of subpressive Ang II infusion. Although phenylephrine led to increased astrogliosis, it did not affect Iba-1 expression. Pressive Ang II stimulated TNF-α production in the hippocampus, and daily treatment with hydralazine prevented this increase. Hydralazine also reduced GFAP and Iba-1 levels. With longer perfusion (14 days), subpressive Ang II led to some but not all the inflammatory changes detected with the pressive doses, mainly an increase in CD68 and Iba-1 but not of GFAP or TNF-α.ConclusionsBlood pressure and Ang II differentially contribute to hippocampal inflammation in mice. Control of blood pressure and Ang II levels should prevent or reduce brain inflammation and therefore brain dysfunctions associated with hypertension.

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

Publications

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

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