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

Abstract Background SARS-CoV-2 infects cells via the ACE2 receptor, whose downstream effects “counterbalance” the classical renin angiotensin aldosterone system (RAAS). It is uncertain to what extent circulating RAAS biomarker levels differ in persons with and throughout COVID-19. 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 versus 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 two 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 were neither different at the two COVID-19 case timepoints nor did they differ in COVID-19 cases vs. controls. Additional adjustment for BMI did not changes 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.