COVID-19: Direct and Indirect Mechanisms of Statins.

Abstract

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-β and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.

• Authors: Agnieszka Pawlos, Mateusz Niedzielski, Paulina Gorzelak-Pabiś, Marlena Broncel, Ewelina Woźniak
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 8 (Apr 17 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33920709 (Publication Type: Journal Article, Review)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors

Topics

• Animals
• COVID-19 (complications)
• Endothelium (drug effects)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Inflammation (complications, drug therapy)
• Lipid Metabolism (drug effects)
• Macrophage Activation (drug effects)
• Pulmonary Fibrosis (complications, drug therapy)
• SARS-CoV-2 (drug effects)
• Thrombosis (complications, drug therapy)
• COVID-19 Drug Treatment