Statins in COVID-19 Therapy

Abstract

Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins' pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial.

Keywords: COVID-19; SARS-CoV-2; pleiotropic effects; statins; therapy.

Figure 1

Mechanisms of action of the proposed COVID-19 therapies. 1. Chloroquine acts via deprivation of formation of the clathrin complexes during SARS-CoV-2 endocytosis and via interruption of post-translation modification of the virus proteins. 2. Lopinavir/ritonavir inhibits virus protease and subsequently impairs virus uncoating. 3. Remdesivir and favipiravir are both antimetabolites that deprivate RNA polymerase function, which results in the premature termination of viral RNA transcription. 4. Tocilizumab is a monoclonal antibody against the interleukin-6 receptor. 5. Colchicine and zinc prevent cytokine storm development. 6. Convalescent plasma contains antibodies capable of binding to and destroying the virus. Created with BioRender.com.

Figure 2

Molecular mechanisms of statins activity in SARS-Cov-2 infection.

Figure 3

Major mechanisms of statin action in COVID-19 treatment. SARS-CoV-2 infection leads to three major disfunctions: (i) activation of coagulation cascade, (ii) endothelial damage and (iii) cytokine storm. Statins are able to protect organism or at least decrease negative effects of SARS-CoV-2 infection. Created with BioRender.com.