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

Nisha I Parikh; Folagbayi Arowolo; Matthew S Durstenfeld; Gregory Nah; Joyce Njoroge; Eric Vittinghoff; Carlin S Long; Peter Ganz; David Pearce; Priscilla Hsue; Alan H S Wu; Negin Hajizadeh; Kathleen D Liu; Kara L Lynch

doi:10.1210/jendso/bvac144

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

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

Authors

Affiliations

¹ Department of Medicine, University of California San Francisco, Division of Cardiology, San Francisco, CA 941432, USA.
² Department of Laboratory Medicine, University of California San Francisco, Division of Cardiology, Zuckerberg San Francisco General Hospital, San Francisco, CA 941103, USA.
³ Department of Medicine, University of California San Francisco, Division of Cardiology, Zuckerberg San Francisco General Hospital, San Francisco, CA 941104, USA.
⁴ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 941585, USA.
⁵ Division of Nephrology, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA 941436, USA.
⁶ Hofstra Northwell School of Medicine, Department of Medicine, Manhasset, NY 110307, USA.
⁷ Division of Critical Care Medicine, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA 941431, USA.

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.

Abstract

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