The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme

Abstract

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the "classic" renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

Keywords: COVID-19; SARS-CoV-2; cardiovascular disease; diabetes mellitus; hypertension; metabolic syndrome; obesity; older age; overweight; renin-angiotensin system.

Figure 1

Overweight/obesity, renin-angiotensin-system, and lung injury caused by SARS-CoV-2. ACE, angiotensin-converting-enzyme; Ang, angiotensin; AT1R, angiotensin II type 1 receptor; Mas R, Mas receptor.

Figure 2

Identikit of the patient at risk for severe COVID-19: “classic RAS” inappropriate activation in a context of lower ACE2 activity as a common feature. Health conditions, cardiometabolic comorbidities, and their assumed relative risk [5,25,43,85,107,117]. a: for patients aged ≥ 75 years.