Expression of ACE2, Soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1-7) Is Modulated in COVID-19 Patients

• Published in: Frontiers in immunology 2021-06, Vol.12, p.625732-625732
• Main Authors: Osman, Ikram Omar, Melenotte, Cléa, Brouqui, Philippe, Million, Matthieu, Lagier, Jean-Christophe, Parola, Philippe, Stein, Andréas, La Scola, Bernard, Meddeb, Line, Mege, Jean-Louis, Raoult, Didier, Devaux, Christian A
• Format: Article
• Language: English
• Subjects: ACE2 (Angiotensin Converting Enzyme-2); Adult; Angiotensin I - blood; Angiotensin II - blood; Angiotensin-Converting Enzyme 2 - blood; Angiotensin-Converting Enzyme 2 - genetics; Bacteriology; Cardiology and cardiovascular system; COVID-19; COVID-19 - blood; COVID-19 - virology; Emerging diseases; Female; Gene Expression Profiling; HLA-DR Antigens; Human health and pathology; Humans; Hypertension; Immunology; Infectious diseases; Life Sciences; Lipopolysaccharide Receptors; Male; Microbiology and Parasitology; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Parasitology; Peptide Fragments - blood; Pilot Projects; Prospective Studies; Renin – Angiotensin – Aldosterone System; RNA, Messenger; SARS – CoV – 2; Virology; Virus Shedding
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.625732

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.