The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients

Vicenzi, Marco; Ruscica, Massimiliano; Iodice, Simona; Rota, Irene; Ratti, Angelo; Cosola, Roberta Di; Bollati, Valentina; Corsini, Alberto; Aliberti, Stefano; Blasi, Francesco

doi:10.21203/rs.3.rs-45837/v1

Cited by 5 publications

(1 citation statement)

References 12 publications

(22 reference statements)

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“…Another investigation in a cohort of 306 COVID-19 patients revealed that elevated plasma sACE2 from COVID-19 patients was significantly associated with severe forms of disease, particularly in hospitalized patients intubated at the time of sample collection (Kragstrup et al, 2021). ARDS in patients with COVID-19 was found associated with an increase in blood pressure and decrease in serum potassium concentration (Vicenzi et al, 2020). Surprisingly, another recent report suggests a significant reduction of Ang II concentration and increased Ang-(1-7) in COVID-19 patients (Martins et al, 2021).…”

Section: Modulation Of Ace2 and Other Actors Of The Ras In Covid-19 P...mentioning

confidence: 99%

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Devaux

Camoin-Jau

2022

Front. Microbiol.

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It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled “ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome”), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients’ therapy.

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Section: Modulation Of Ace2 and Other Actors Of The Ras In Covid-19 P...mentioning

confidence: 99%

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Devaux

Camoin-Jau

2022

Front. Microbiol.

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Association between Mineralocorticoid Receptor Antagonist and Mortality in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis

et al. 2022

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Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134–1.117, p = 0.079).

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The Role of Multidisciplinary Approaches in the Treatment of Patients with Heart Failure and Coagulopathy of COVID-19

Gryglewska-Wawrzak

Cienkowski

Cienkowska

et al. 2023

JCDD

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Coronavirus disease 2019 (COVID-19) is a severe respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heart failure (HF) is associated with a worse prognosis for patients with this viral infection, highlighting the importance of early detection and effective treatment strategies. HF can also be a consequence of COVID-19-related myocardial damage. To optimise the treatment of these patients, one needs to understand the interactions between this disease and viruses. Until now, the validity of the screening for cardiovascular complications after COVID-19 has not been confirmed. There were also no patients in whom such diagnostics seemed appropriate. Until appropriate recommendations are made, diagnosis procedures must be individualised based on the course of the acute phase and clinical symptoms reported or submitted after COVID-19. Clinical phenomena are the criteria for determining the recommended test panel. We present a structured approach to COVID-19 patients with heart involvement.

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The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients

Cited by 5 publications

References 12 publications

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Association between Mineralocorticoid Receptor Antagonist and Mortality in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis

The Role of Multidisciplinary Approaches in the Treatment of Patients with Heart Failure and Coagulopathy of COVID-19

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