Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence

Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.