High Angiotensin-Converting Enzyme and Low Carboxypeptidase N Serum Activity Correlate with Disease Severity in COVID-19 Patients.

Phil-Robin Tepasse,Simone König,Richard Vollenberg,Nico Steinebrey

doi:10.3390/jpm12030406

Phil-Robin Tepasse, Simone König + Show 2 more

Open Access

https://doi.org/10.3390/jpm12030406

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Abstract

(1) Background: Angiotensin-converting enzyme 2 (ACE2) is a functional receptor of SARS-CoV-2 and counter-balances ACE in the renin–angiotensin system (RAS). An imbalance of the RAS could be associated with severe COVID-19 progression. (2) Methods: Activities of serum proteases angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) for 45 hospitalized and 26 convalescent COVID-19 patients were investigated vs. healthy controls using labeled bradykinin (DBK) degradation with and without inhibition by captopril as a read-out. Data were correlated to clinical parameters. (3) Results: DBK degradation and CPN activity were significantly reduced gender-independently in COVID-19 and returned to normal during convalescence. ACE activity was over-active in severe disease progression; product DBK1-5 was significantly increased in critically ill patients and strongly correlated with clinical heart and liver parameters. ACE inhibitors seemed to be protective, as DBK1-5 levels were normal in moderately ill patients in contrast to critically ill patients. (4) Conclusions: CPN and ACE serum activity correlated with disease severity. The RAS is affected in COVID-19, and ACE could be a therapeutic target. Further proof from dedicated studies is needed.

Highlights

Angiotensin-converting enzyme 2 (ACE2) counter-balances the renin–angiotensin system (RAS), an important endocrine, paracrine and intracrine system involved in blood pressure homeostasis [1,2]
Our study demonstrated the correlation of the activity of the serum proteases carboxypeptidase N (CPN)
The observation that none of the hospitalized patients taking ACE inhibitors (ACEIs) or ARB died in contrast to half of the untreated hypertonic patients supported the notion that angiotensin-converting enzyme (ACE) might be a therapeutic target

Summary

Introduction

Angiotensin-converting enzyme 2 (ACE2) counter-balances the renin–angiotensin system (RAS), an important endocrine, paracrine and intracrine system involved in blood pressure homeostasis [1,2]. It is a functional receptor of severe acute respiratory syndrome coronavirus (SARS-CoV) and required for host cell entry and subsequent viral replication (Figure 1) [3]. SARS-CoV-2, the pathogenic agent responsible for the ongoing COVID-19 pandemic, seems to recognize human ACE2 even more efficiently than. SARS-CoV, increasing the ability of the virus to transmit from person to person [4]. The involvement of ACE2 and the RAS in SARS-CoV-2 infection led to controversial discussions in the general public concerning a potentially increased risk for worse COVID-19 symptoms in patients taking antihypertensive medication [5,6]. Slight, albeit not significant, reduction in the risk of mortality was reported [7]

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