Molecular Mimicry of the Viral Spike in the SARS-CoV-2 Vaccine Possibly Triggers Transient Dysregulation of ACE2, Leading to Vascular and Coagulation Dysfunction Similar to SARS-CoV-2 Infection

Viruses. 2023 Apr 25;15(5):1045. doi: 10.3390/v15051045.

Abstract

The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of rare cases of cardiovascular complications after mass vaccination using such formulations. Cases of high blood pressure have also been reported but were rarely documented under perfectly controlled medical supervision. The press release of these warning signals triggered a huge debate over COVID-19 vaccines' safety. Thereby, our attention was quickly focused on issues involving the risk of myocarditis, acute coronary syndrome, hypertension and thrombosis. Rare cases of undesirable post-vaccine pathophysiological phenomena should question us, especially when they occur in young subjects. They are more likely to occur with inappropriate use of mRNA vaccine (e.g., at the time when the immune response is already very active during a low-noise infection in the process of healing), leading to angiotensin II (Ang II) induced inflammation triggering tissue damage. Such harmful effects observed after the COVID-19 vaccine evoke a possible molecular mimicry of the viral spike transiently dysregulating angiotensin converting enzyme 2 (ACE2) function. Although the benefit/risk ratio of SARS-CoV-2 spike mRNA vaccine is very favorable, it seems reasonable to suggest medical surveillance to patients with a history of cardiovascular diseases who receive the COVID-19 vaccine.

Keywords: ACE2; COVID-19; coagulation; coronavirus; hypertension; renin-angiotensin system; therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Blood Coagulation Disorders*
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / prevention & control
  • Humans
  • Hypertension*
  • Molecular Mimicry
  • Peptidyl-Dipeptidase A / metabolism
  • Renin-Angiotensin System / physiology
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • COVID-19 Vaccines
  • Angiotensin-Converting Enzyme 2
  • Peptidyl-Dipeptidase A
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This work was supported by the French Government under the “Investissements d’avenir” (Investments for the Future) program managed by the Agence Nationale de la Recherche (French ANR: National Agency for Research; reference: Méditerranée Infection 10-IAHU-03), and annual funds from Aix-Marseille university and IRD to the MEPHI research unit (Director: Professor Jean-Christophe Lagier). Other funding sources were limited to the salaries of the authors (Centre National de la Recherche Scientifique for C.A.D., Assistance Publique Hôpitaux de Marseille for L.C.-J.), with no other role or involvement.