Biological Actions, Implications, and Cautions of Statins Therapy in COVID-19

Abstract

The Coronavirus Disease 2019 (COVID-19) showed worse prognosis and higher mortality in individuals with obesity. Dyslipidemia is a major link between obesity and COVID-19 severity. Statins as the most common lipid regulating drugs have shown favorable effects in various pathophysiological states. Importantly, accumulating observational studies have suggested that statin use is associated with reduced risk of progressing to severe illness and in-hospital death in COVID-19 patients. Possible explanations underlie these protective impacts include their abilities of reducing cholesterol, suppressing viral entry and replication, anti-inflammation and immunomodulatory effects, as well as anti-thrombosis and anti-oxidative properties. Despite these benefits, statin therapies have side effects that should be considered, such as elevated creatinine kinase, liver enzyme and serum glucose levels, which are already elevated in severe COVID-19. Concerns are also raised whether statins interfere with the efficacy of COVID-19 vaccines. Randomized controlled trials are being conducted worldwide to confirm the values of statin use for COVID-19 treatment. Generally, the results suggest no necessity to discontinue statin use, and no evidence suggesting interference between statins and COVID-19 vaccines. However, concomitant administration of statins and COVID-19 antiviral drug Paxlovid may increase statin exposure and the risk of adverse effects, because most statins are metabolized mainly through CYP3A4 which is potently inhibited by ritonavir, a major component of Paxlovid. Therefore, more clinical/preclinical studies are still warranted to understand the benefits, harms and mechanisms of statin use in the context of COVID-19.

Statins in hospitalized COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

“…4,28 These supposed protective effects of statins were attributed to: reducing cholesterol, inhibition of viral entry and replication, anti-inflammatory and immunomodulatory, as well antithrombotic and antioxidant. 27,28 However, the results of most RCTs and this meta-analysis failed to demonstrate these benefits. The vast majority of meta-analyses of statins for COVID-19 included primarily observational studies and reached similar conclusions that statins reduce mortality.…”

“…Observational studies have shown that statins use is associated with a reduced risk of disease progression and in-hospital death in patients with COVID-19. 4,28 These supposed protective effects of statins were attributed to: reducing cholesterol, inhibition of viral entry and replication, anti-inflammatory and immunomodulatory, as well antithrombotic and antioxidant. 27,28 However, the results of most RCTs and this meta-analysis failed to demonstrate these benefits.…”

SARS-CoV-2 infection-related deregulation of blood lipids in a patient with -/-LDLR familial homozygous hypercholesterolemia: A case report

“…Statins have been considered as a potentially beneficial drug class in COVID-19 patients, since pre-hospital statin use has been associated with reduced inflammatory responses, as evident by lower levels of CRP and IL-6 14 . It has been proposed that statins might significantly reduce the attachment and internalization of SARS-CoV-2 by lowering membrane cholesterol levels 14 , 15 . In addition, statins exert antithrombotic and antioxidative properties, which could be of clinical importance in COVID-19 patients, who present a pro-thrombotic state 15 .…”

“…It has been proposed that statins might significantly reduce the attachment and internalization of SARS-CoV-2 by lowering membrane cholesterol levels 14 , 15 . In addition, statins exert antithrombotic and antioxidative properties, which could be of clinical importance in COVID-19 patients, who present a pro-thrombotic state 15 . Other hypolipidemic treatments, such as fibrates and niacin, have been tested in clinical trials as potential therapeutic interventions in patients with COVID-19, with limited results 16 .…”

Mapping the Lipid Signatures in COVID-19 Infection: Diagnostic and Therapeutic Solutions

“…11 By doing so, statins help lower cholesterol levels, prevent coronavirus infection, and attenuate COVID-19-related inflammation. 124 Statins such as atorvastatin (19, Figure 5), lovastatin (20, Figure 5), and simvastatin (21, Figure 5) can also prevent COVID-19-related cardiovascular complications, 125,126 Figure 5. However, statins have also been shown to enhance ACE2 expression in the heart of experimental models, 127 raising safety concerns regarding their use in patients with COVID-19.…”