PROS

AREA OF INTEREST

Action of statins

CLINICAL EFFECTS IN PATIENTS COVID-19

Immunomodulation [10]

Stabilization of MyD88 levels during hypoxia and stress, mitigating the action of NF-kB

Potential to reduce the severity of SARS-CoV2 infection

Inflammation [13] [14]

1) Reduction of LDL cholesterol levels, thereby reducing direct LDL cholesterol mediated inflammation

2) Inhibition of prenylation of G proteins, leading to down-regulation of NF-kB, suppression of pro-inflammatory cytokines (TNF a, IL-6) and chemokines (IL-8)

Potential role in reduction of SARS-CoV2 induced lung injury and protection from cytokine storm

Oxidative Stress [18]

Reduction of oxidative injury/maintenance of the redox balance of the endothelium by:

1) Upregulation of nitric oxide syntliase

2) Suppression of pro-oxidant enzymes (NADPH oxidase)

Potential role in reduction of SARS-CoV2 induced lung injury

Thrombosis [21] [22]

1. Anti-platelet effect (Lipid dependent and lipid independent mechanisms)

2. Weak anti-thrombotic effect

1) Prevents the conversion of factor X to Xa by down regulating tissue factor

2) Uoregulation of thrombomodulin to bind thrombin

Potential to reduce/prevent venous and arterial thrombus formation

Membrane (lipid) rafts [23]

Disruption of lipid rafts by depletion of cholesterol from the plasma membrane, which might alter the assembly of angiotensin converting enzyme 2 receptors (act as co-receptors for SARS-CoV2 entry into the cell)

Theoretical possibility ofreducing viral entry, leading to low viral titres and infectivity

(ACE2) [4] [24]

Upregulation of expression of ACE2

Potential to reduce SARS-CoV2 induced lung injury mediated by excess Angiotensin-11

SARS-CoV2 main protease [26]

Efficient inhibitors of SARS-CoV2 main protease (Computational molecular docking method)

Potential to directly inhibit the virus, reducing viral load

CONS

Tot cholesterol/ LDL cholesterol levels [7]

Reduction of serum total and LDL cholesterol

Speculated that this might increase morbidity/mortality from SARS-CoV2 infection, as elevated illL cholesterol is protective since illL particles adhere to and inactivate microorganisms and their toxins

Immunomodul ation [10]

Inhibition of MyD88 expression

Speculated to reduce innate immunity response, thereby worsening infection

Angiotensin converting enzyme 2 (ACE2) [24]

Upregulation of expression of ACE2

Potential to increase SARS-CoV2 entry into cells

Myositis and liver dysfunction [31] [32] [33] [34]

I. Mild elevation of liver enzymes in 10%, and elevation >3 times upper limit of normal in 1% - 3% 2. Myalgia in 2% - 7%

Detrimental effect in people with COVID-19 with skeletal muscle symptoms or liver dysfunction

Drug interactions [35] [37]

Inhibition of cytochrome P-450 group of enzymes by protease inhibitors used in COVID-19 may significantly increase statin levels

Increased risk of toxicity: myopathy and rhabdomyolysis