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. 2020 Jun 8;24(1):318.
doi: 10.1186/s13054-020-03055-6.

Blocking mineralocorticoid receptor with spironolactone may have a wide range of therapeutic actions in severe COVID-19 disease

Lucas Liaudet  1 , Csaba Szabo  2
Affiliations

Blocking mineralocorticoid receptor with spironolactone may have a wide range of therapeutic actions in severe COVID-19 disease

Lucas Liaudet et al. Crit Care. .
No abstract available

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Conflict of interest statement

No competing interests.

Figures

Fig. 1
Fig. 1
Sites of potential pharmacological actions of spironolactone in COVID-19 ARDS. SARS-CoV-2 infects type II alveolar epithelial cells (type II AEC) via interaction between its spike S protein and ACE2 receptor, promoting internalization and degradation of ACE2 and pulmonary ACE/ACE2 imbalance. In turn, the degradation of angiotensin II (AT II) into angiotensin 1–7 (AT1–7) is prevented (dotted lines), reducing anti-inflammatory signaling through the Mas receptor (MasR), and promoting pro-inflammatory AT II signaling through the angiotensin receptor type I (AT1R) in vascular endothelial cells. Increased AT II results in aldosterone formation, which signals through the mineralocorticoid receptor (MR), leading to vascular inflammation and immune cells activation. MR activation polarizes macrophages towards the M1 pro-inflammatory phenotype (M1Mϕ), favors CD4+ lymphocytes differentiation towards pro-inflammatory Th17 cells, and induces cytotoxic IFNγ+-CD8+ lymphocytes. The development of a hyper-inflammatory state may trigger ARDS. MR inhibition with spironolactone may interrupt the deleterious actions of aldosterone. Furthermore, via its anti-androgenic effects, spironolactone may decrease the expression of TMPRSS2, a serine protease priming the S protein for its interaction with ACE2. Abbreviations: ACE, angiotensin-converting enzyme; AndR, androgen receptor; AT I, angiotensin I; AT II, angiotensin II; AT1–7, angiotensin 1–7; AT1R, angiotensin receptor type I; MR, mineralocorticoid receptor; MasR, Mas receptor; NO, nitric oxide; ROS, reactive oxygen species; TMPRSS2, transmembrane serine protease 2
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