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COVID-19: Direct and Indirect Mechanisms of Statins

Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Sotiris K Hadjikakou
Int. J. Mol. Sci. 2021, 22(8), 4177; https://doi.org/10.3390/ijms22084177
Received: 24 March 2021 / Revised: 10 April 2021 / Accepted: 16 April 2021 / Published: 17 April 2021
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: statins; COVID-19; SARS-CoV-2; macrophages activation syndrome (MAS); main protease (Mpro); RNA-dependent RNA polymerase (RdRp); TLR 4; IL-6; ACE2; thrombosis statins; COVID-19; SARS-CoV-2; macrophages activation syndrome (MAS); main protease (Mpro); RNA-dependent RNA polymerase (RdRp); TLR 4; IL-6; ACE2; thrombosis
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MDPI and ACS Style

Pawlos, A.; Niedzielski, M.; Gorzelak-Pabiś, P.; Broncel, M.; Woźniak, E. COVID-19: Direct and Indirect Mechanisms of Statins. Int. J. Mol. Sci. 2021, 22, 4177. https://doi.org/10.3390/ijms22084177

AMA Style

Pawlos A, Niedzielski M, Gorzelak-Pabiś P, Broncel M, Woźniak E. COVID-19: Direct and Indirect Mechanisms of Statins. International Journal of Molecular Sciences. 2021; 22(8):4177. https://doi.org/10.3390/ijms22084177

Chicago/Turabian Style

Pawlos, Agnieszka, Mateusz Niedzielski, Paulina Gorzelak-Pabiś, Marlena Broncel, and Ewelina Woźniak. 2021. "COVID-19: Direct and Indirect Mechanisms of Statins" International Journal of Molecular Sciences 22, no. 8: 4177. https://doi.org/10.3390/ijms22084177

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