Teaching Old Drugs New Tricks: Statins for COVID-19?

Abstract

The COVID-19 pandemic has driven unprecedented efforts to identify existing treatments that can be quickly and effectively repurposed to reduce morbidity and mortality. In this issue of Cell Metabolism, Zhang et al. (2020) report an association between statin use and improved outcomes in a large observational study of hospitalized COVID-19 patients. Given the widespread availability, low cost, and safety of statins, this promising result should be further investigated in randomized controlled trials.

Figure 1

Drug Repurposing for COVID-19 and Beyond (A) Promising repurposed drugs for COVID-19 presented on a theoretical time versus severity graph. Blue represents the COVID-19 cases in which a mortality benefit has been demonstrated for dexamethasone (hospitalized patients on supplemental oxygen therapy or ventilation). Gray represents the COVID-19 cases in which a surrogate outcome benefit has been demonstrated for remdesivir (greater benefit if given earlier in disease course). Red represents the COVID-19 cases in which observational studies have suggested a potential mortality benefit for statins and famotidine (hospitalized patients). Like statins, a well-matched retrospective cohort study of famotidine suggested improved outcomes in hospitalized COVID-19 patients (Freedberg et al., 2020). (B) A conceptual framework for drug repurposing. Drug repurposing candidates are preliminarily identified through laboratory investigation of drug targets, mining of published literature, and high-throughput drug screens. While the success rate of high-throughput drug screens has been low historically, the basic understanding of SARS-CoV-2 biology, as well as the large number of efforts, likely increases the potential for success. These candidates can be validated and refined through orthogonal in vitro and in vivo studies. Observational studies of widely used drugs are often performed to search for associations between drug exposure and outcomes. In this case, the observational study by Zhang et al. provided the first indication that statins may be effective in COVID-19 (red border highlights this aspect of the framework). Open-label, single-arm, or preferably, randomized controlled trials are then performed to investigate efficacy (and safety) and determine if the drug should be adopted in clinical practice and/or given regulatory approval for the new indication. In parallel, it is important to track all drugs being used off-label and experimentally to identify promising candidates for further investigation. The CORONA Project tracks off-label and experimental drugs used in COVID-19 (red box). There is very high interest in drug repurposing for COVID-19 from multiple sectors, including the US Food & Drug Administration (FDA), which will likely speed up the time from candidate identification to approval.