Introduction
In December 2019, SARS-CoV-2 was identified as a novel coronavirus implicated in a cluster of viral pneumonia cases in Wuhan, China. This pathogen has since disseminated across the world in a pandemic that has led to severe health and economic consequences for the global community. This has led to a sense of urgency in finding therapies that can alleviate the death toll and reduce the burden on hospitals, especially intensive care units with their limited and expensive resources. Drug development is a timely and painstaking process from the laboratory to the dispensary, hence creating a safe and effective antiviral de novo may not meet the urgency of the moment. As a result, scientific attention has been directed toward agents already widely used, with known safety and pharmacological profiles.[1]
Hydroxychloroquine received an intense amount of attention early in this pandemic, following uncontrolled data suggesting that the related compound chloroquine improved pulmonary outcomes in China.[2] Excitement mounted as the world wondered whether these cheap and safe medications would indeed save lives. Indeed, government health policies across the world promoted the immediate use of hydroxychloroquine for patients with COVID-19. Numerous clinical trials were initiated to study the safety and efficacy of hydroxychloroquine utilizing various dosing strategies (Figure 1). A majority of early trials utilized standard hydroxychloroquine doses approved for chronic treatment of rheumatic diseases ranging from 400 to 600 mg daily (Table 1). Our group hypothesized a high-dose short-term hydroxychloroquine dosing strategy would provide enhanced treatment efficacy due to more rapid increases in serum drug concentrations. We therefore proposed a study to determine if high-dose hydroxychloroquine (1200 mg daily for five days) was well tolerated and demonstrated activity in ambulatory patients with mild COVID-19.
Herein we review the pharmacologic basis and design of our trial, the outcomes of other studies investigating hydroxychloroquine in COVD19 to date as well as discuss the challenges faced by studies evaluating hydroxychloroquine in COVID-19 in the current environment.