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. 2022 Sep 22;6(12):bvac144.
doi: 10.1210/jendso/bvac144. eCollection 2022 Oct 26.

Hospitalized Patients With COVID-19 Have Higher Plasma Aldosterone-Renin Ratio and Lower ACE Activity Than Controls

Nisha I Parikh  1 , Folagbayi Arowolo  2 , Matthew S Durstenfeld  3 , Gregory Nah  1 , Joyce Njoroge  1 , Eric Vittinghoff  4 , Carlin S Long  1 , Peter Ganz  1 , David Pearce  5 , Priscilla Hsue  3 , Alan H S Wu  2 , Negin Hajizadeh  6 , Kathleen D Liu  5   7 , Kara L Lynch  2
Affiliations

Hospitalized Patients With COVID-19 Have Higher Plasma Aldosterone-Renin Ratio and Lower ACE Activity Than Controls

Nisha I Parikh et al. J Endocr Soc. .

Abstract

Context: SARS-CoV-2 infects cells via the angiotensin converting enzyme 2 (ACE2) receptor, whose downstream effects "counterbalance" the classical renin angiotensin aldosterone system (RAAS).

Objective: We aimed to determine to what extent circulating RAAS biomarker levels differ in persons with and without COVID-19 throughout the disease course.

Methods: We measured classical (renin, aldosterone, aldosterone/renin ratio [ARR], Ang2, ACE activity) and nonclassical (ACE2, Ang1,7) RAAS biomarkers in hospitalized COVID-19 patients vs SARS-CoV-2 negative controls. We compared biomarker levels in cases with contemporaneous samples from control patients with upper respiratory symptoms and a negative SARS-CoV-2 PCR test. To assess RAAS biomarker changes during the course of COVID-19 hospitalization, we studied cases at 2 different times points ∼ 12 days apart. We employed age- and sex-adjusted generalized linear models and paired/unpaired t tests.

Results: Mean age was 51 years for both cases (31% women) and controls (50% women). ARR was higher in the first sample among hospitalized COVID-19 patients vs controls (P = 0.02). ACE activity was lower among cases at their first sample vs controls (P = <0.001). ACE2 activity, Ang 1,7, and Ang2 did not differ at the 2 COVID-19 case time points and they did not differ in COVID-19 cases vs controls. Additional adjustment for body mass index (BMI) did not change our findings.

Conclusions: High ARR, independent of BMI, may be a risk marker for COVID-19 hospitalization. Serum ACE activity was lower in patients with COVID-19 vs controls at the beginning of their hospitalization and then increased to similar levels as controls, possibly due to lung injury, which improved with inpatient disease management.

Keywords: ACE-2; COVID-19; biomarkers; hospitalization; obesity; renin-aldosterone ratio; renin-angiotensin aldosterone system; severity.

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Figures

Figure 1.
Figure 1.
Renin-angiotensin aldosterone system and COVID-19.
Figure 2.
Figure 2.
(A) Box and whisker plots of log aldosterone to renin ratio. (B) Box and whisker plots of log aldosterone. (C) Box and whisker plots of log renin.
Figure 3.
Figure 3.
(A) Box and whisker plots of log ACE activity. (B) Box and whisker plots of log ACE2. (C) Box and whisker plots of log ACE2 activity/ACE activity.
Figure 4.
Figure 4.
(A) Box and whisker plots of log Ang 1,7. (B) Box and whisker plots of log Ang2. (C) Box and whisker plots of log Ang1,7/Ang2.
See this image and copyright information in PMC

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