Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies

Viruses. 2021 Sep 21;13(9):1880. doi: 10.3390/v13091880.

Abstract

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.

Keywords: SARS-CoV-2; apoptosis; energy metabolism; immune response; myocardial damage; myocarditis; treatment of viral infection; viral docking; viral replication; viroporin.

Publication types

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

MeSH terms

  • Apoptosis
  • Autophagy
  • COVID-19 / complications*
  • COVID-19 / virology*
  • Disease Management
  • Disease Susceptibility
  • Endothelial Cells / ultrastructure
  • Endothelial Cells / virology
  • Heart Diseases / diagnosis
  • Heart Diseases / etiology*
  • Heart Diseases / therapy
  • Host-Pathogen Interactions / immunology
  • Humans
  • Myocarditis / diagnosis
  • Myocarditis / etiology
  • Myocarditis / therapy
  • SARS-CoV-2 / physiology*
  • Viroporin Proteins
  • Virus Replication

Substances

  • Viroporin Proteins