Obesity and COVID-19: 2 The ominous duet affecting the renin-angiotensin system.

Luzi, Livio; Bucciarelli, Loredana; Ferrulli, Anna; Terruzzi, Ileana; Massarini, Stefano

The World population is facing a health challenge never seen since the Spanish influenza of one hundred years ago. During the last months, the scientific community has been debating on the potential harmful effect of Angiotensin-converting-enzyme inhibitors (ACEi) or Angiotensin II receptor Type 1 receptor blockers (AT1-Receptor blockers, ARBs) during the COVID-19 pandemic. That is because the S spike protein of SARS8 CoV viruses utilizes the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter alveolar epithelial cells. Obesity, often associated to type 2 Diabetes, was shown to worsen the prognosis of SARS-CoV2 infection. Herein we discuss the complex interaction between the Renin-Angiotensin-Aldosterone System (RAAS), its receptors, and the interaction with the Kallikrein-Kinin-System (KKS) and the potential activation of the coagulation cascade. Alteration of the equilibrium between the RAAS system and the KKS cascade may explain the frequent thromboembolic complications of COVID-19 mainly seen in obese and diabetic-obese patients. In contrast, angiotensin (1-7) contributes to maintaining a correct balance between RAAS and KKS system. Our conclusion is that the higher mortality rate in patients with obesity is linked to the alteration of RAS and RAS-KKS interaction consequent to SARS-CoV2-cell entrance. At present, no data support the necessity of modifying ACEi or ARBs treatment in hypertensive patients.