The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study

Abstract

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. Methods. Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients’ clinical courses. Results. Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. Conclusions. Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.

COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection

“…As a result of the viral tropism to the kidneys, acute renal injury was found to be the second most observed COVID-19 complication in the USA (22.2%) [ 77 ] and China (25.2%) [ 67 ]. Thus, there is compelling evidences that patients with acute kidney injury at admission exhibit activation of RAAS, as documented by higher plasmatic renin and aldosterone levels and lower urinary sodium levels in patients with acute kidney injury [ 109 ], as well as the association of plasmatic aldosterone and C-reactive protein levels and COVID-19 severity [ 110 ]. Since hypokalaemia was found to be prevalent in patients with COVID-19 pneumonia (~ 30%) and is an indicator of RAAS activity, it was suggested that hypokalaemia could be used as a surrogate marker of COVID-19 progression and an independent risk factor for invasive mechanical ventilation requirement [ 111 ].…”

SARS-CoV-2, ACE2 expression, and systemic organ invasion

“…Early data on kidney function have shown that patients who are admitted to the hospital for COVID-19 have an increase in protein in the urine (proteinuria) and blood in the urine (hematuria) ( 14 ). Patients with a severe clinical course for COVID-19 show higher circulating renin, ANG II, and aldosterone compared with those with mild COVID-19 clinical complications ( 58 ). Moreover, acute kidney injury (AKI) occurs in nearly 36.6% of SARS-CoV-2-infected patients ( 59 ).…”

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…In addition, potassium canrenoate (the active metabolite of spironolactone) results in concentration (0.1-10 μM)-dependent reductions of the binding of the SARS-CoV-2 spike protein to the ACE2 receptor ( Carino et al, 2020 ). Increased plasma aldosterone levels associated with disease severity in COVID-19 patients ( Villard et al, 2020 ) suggest that MRBs may have beneficial effects in COVID-19. A recent study concluded that canrenone decreased all-cause mortality and improved the clinical outcome in a small cohort of 30 COVID-19 patients with diseases ranging from moderate to severe (M. Vicenzi et al, 2020 ).…”