A lower aldosterone/renin ratio (OR 0.73) and higher soluble ACE2 levels (OR 1.33) were independently associated with severe COVID-19, defined as ICU admission or death.
Observational (n=188)
No
Do soluble ACE2 levels, aldosterone/renin ratio, and TMPRSS2 polymorphisms predict disease severity in adults hospitalized with COVID-19?
High soluble ACE2, a low aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype are independent predictors of severe COVID-19, independent of RAAS blocker use.
Effect estimate: OR 0.73 (95% CI 0.59-0.89)
p-value: p=0.0037
Abstract Background The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered safe. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. Methods Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma), and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. Measurements and main results Of the 188 patients that were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels, and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. Conclusion High sACE2, a low aldosterone/renin ration, and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. Trial registration: retrospectively registered
Akınら（Sat,）はCOVID-19において観察研究を実施した（n=188）。アルドステロン/レニン比は重症COVID-19（ICU入院および/または全死因死亡）について評価された（OR 0.73、95% CI 0.59-0.89、p=0.0037）。低いアルドステロン/レニン比（OR 0.73）および高い可溶性ACE2レベル（OR 1.33）は、ICU入院または死亡と定義される重症COVID-19と独立して関連していた。