COVID-19, vaccines and deficiency of ACE2 and other angiotensinases. Closing the loop on the "Spike effect"

Eur J Intern Med. 2022 Sep:103:23-28. doi: 10.1016/j.ejim.2022.06.015. Epub 2022 Jun 22.

Abstract

The role of a dysregulated renin-angiotensin system (RAS) in the pathogenesis of COVID-19 is well recognized. The imbalance between angiotensin II (Ang II) and Angiotensin1-7 (Ang1,7) caused by the interaction between SARS-CoV-2 and the angiotensin converting enzyme 2 (ACE2) receptors exerts a pivotal role on the clinical picture and outcome of COVID-19. ACE2 receptors are not the exclusive angiotensinases in nature. Other angiotensinases (PRCP, and POP) have the potential to limit the detrimental effects of the interactions between ACE2 and the Spike proteins. In the cardiovascular disease continuum, ACE2 activity tends to decrease, and POP/PRCP activity to increase, from the health status to advanced deterioration of the cardiovascular system. The failure of the counter-regulatory RAS axis during the acute phase of COVID-19 is characterized by a decrease of ACE2 expression coupled to unchanged activity of other angiotensinases, therefore failing to limit the accumulation of Ang II. COVID-19 vaccines increase the endogenous synthesis of SARS-CoV-2 spike proteins. Once synthetized, the free-floating spike proteins circulate in the blood, interact with ACE2 receptors and resemble the pathological features of SARS-CoV-2 ("Spike effect" of COVID-19 vaccines). It has been noted that an increased catalytic activity of POP/PRCP is typical in elderly individuals with comorbidities or previous cardiovascular events, but not in younger people. Thus, the adverse reactions to COVID-19 vaccination associated with Ang II accumulation are generally more common in younger and healthy subjects. Understanding the relationships between different mechanisms of Ang II cleavage and accumulation offers the opportunity to close the pathophysiological loop between the risk of progression to severe forms of COVID-19 and the potential adverse events of vaccination.

Keywords: ACE2; COVID-19; Olygopeptodases; POP; PRCP; Renin-angiotensin-aldosterone system; SARS-CoV-2; Therapy; Vaccines.

Publication types

  • Review

MeSH terms

  • Aged
  • COVID-19 Vaccines
  • COVID-19*
  • Endopeptidases
  • Humans
  • Peptidyl-Dipeptidase A
  • Renin-Angiotensin System
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Substances

  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • angiotensinase
  • spike protein, SARS-CoV-2
  • Endopeptidases
  • Peptidyl-Dipeptidase A