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.