Statins as an adjunctive therapy for COVID-19: the biological and clinical plausibility

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has infected millions of individuals and has claimed hundreds of thousands of human lives worldwide. Patients with underlying cardiovascular conditions are at high risk for SARS-CoV-2 infection, and COVID-19 patients have high incidence of cardiovascular complications such as acute cardiac injury, arrhythmias, heart failure, and thromboembolism. The disease has no approved proven effective therapy and hence repurposing of existing approved drugs has been considered as the fastest treatment approach. Statins have been shown to exhibit lipid lowering dependent and independent cardiovascular protective effects as well as favorable effects in various other pathophysiological states. These beneficial properties of statins are a result of their multiple pleotropic effects that include, anti-inflammatory, immunomodulatory, antithrombotic and antimicrobial properties. In this review, we provide a comprehensive description of the mechanisms of the pleotropic effects of statins, the relevant pre-clinical and clinical data pertinent to their role in infections and acute lung injury, the possible cardiovascular benefits of statins in COVID-19, and the implications of the therapeutic potential of statins in COVID-19 disease. We conclude with the rationale for conducting randomized controlled trials of statins in COVID-19 disease.

Keywords:

• Statins
• COVID-19
• antiviral
• anti-inflammatory
• acute lung injury
• SARS-CoV-2
• ARDS
• immunomodulatory

Disclosure statement

Dr. O'Horo reports personal fees from Elsevier, Inc, outside the submitted work. Dr. Tleyjeh reports other from pToDate, outside the submitted work. Dr. Badely: Consultant: Abbvie, Nference, Qrativ, Zeno Pharmaceuticals. Other: SAB: Nference, Zentalis. Founder and President, Splissen Therapeutics. Program Director/Principal Investigator Grants. Evaluating the role of the novel apoptosis inhibitor TRAILshort, in maintaining HIV persistence. Funded by National Institute of Allergy and Infectious Diseases. (R01 AI 120698). Prime shock and kill for HIV eradication. Funded by National Institute of Allergy and Infectious Diseases (R01 AI 110173). Ixazomib to reduce HIV reservoir size. Funded by AmFar (109593-62-RGRL). Dr Arabi reports that he is principal investigator on a clinical trial of lopinavir–ritonavir and interferon for Middle East respiratory syndrome (MERS) and that he was a non-paid consultant on therapeutics for MERS-coronavirus (CoV) for Gilead Sciences and SAB Biotherapeutics. He is a co-investigator on the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) and a board member of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Other authors: nothing to disclose.