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.

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review

“…The action mechanism of antiviral drugs is mainly through blocking a certain stage of virus replication and reproduction, such as preventing the virus from entering the host cell (Pawlos et al, 2021), inhibiting the synthesis of the virus (Kumar et al, 2021), and inhibiting the release of the virus (Martin-Sancho et al, 2021), so as to achieve the purpose of inhibiting virus reproduction and controlling virus infection. The antiviral effect of CPMs is through inhibiting the function enzyme of SARS-CoV-2 or binding with the host cell receptor.…”

The protective role of statins in COVID-19 patients: a retrospective observational study

“…The SARS-CoV-2 invades the alveolar epithelial cells through the ACE-2 receptor and undergoes replication. The virus releases numerous cytokines and interleukins, causing a cytokine storm [ 36 – 38 ]. The inflammatory markers cause the respiratory manifestations and as reflected by the laboratory markers in our study.…”

COVID-19 and lipids. The role of lipid disorders and statin use in the prognosis of patients with SARS-CoV-2 infection

“…Several mechanisms by which statins have a positive effect on the prognosis of COVID-19 patients have been described [ 68 ]. There are direct and indirect mechanisms of statin action in relation to SARS-CoV-2 infection [ 69 ].…”