A prediction model for lung involvement using circulating angiotensin converting enzyme-2 and renin levels in COVID-19 patients

Abstract

Introduction: The potential role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of coronavirus disease 2019 (COVID-19) is controversial, with concerns mainly about the part RAAS peptides play in the prediction of progression to more severe disease. Given the importance of COVID-19 prognostication at early disease stages, we established and validated a multivariable risk stratification tool for COVID-19 associated lung involvement by utilizing a combination of RAAS peptides.

Methodology: In this prospective study, circulating renin and angiotensin converting enzyme-2 (ACE-2) levels were measured in 116 COVID-19 patients who were admitted to our hospital from March 30, 2021 to January 24, 2022 and underwent a lung computed tomography (CT) scan. Clinical severity was measured with a national early warning score (NEWS). Associations among RAAS peptides, inflammation-dependent biomarkers, demographic variables, and clinical outcomes were studied using logistic regression and Cox proportional-hazards models.

Results: We assessed 116 COVID-19 patients (mean age 45.1 ± 12.6 years; 51.7% male), of whom 66 (56.9%) had COVID-19 associated pneumonia. Baseline circulating ACE-2 (2.63 ± 0.12 ng/mL) and renin levels (85.04 ± 6.8 ng/L) were lower in patients with COVID-19 related pneumonia compared to patients without pneumonia (6.4 ± 0.7 ng/mL and 211.6 ± 21.9 ng/L, respectively) (p < 0.001 for both). Both RAAS components were found to be significantly related to adverse outcomes, including COVID-19 associated pneumonia and intensive care unit (ICU) admission, in both crude and adjusted multivariable logistic regression analyses.

Conclusions: Circulating ACE-2 and renin levels can predict lung involvement in COVID-19 patients, and they display good correlation and agreement with NEWS.