Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a rational use for prophylaxis of SARS-CoV-2 infection

ABSTRACT

Introduction

Over the last few months, coronavirus disease 2019 (COVID-19) pandemic caused by the novel coronavirus SARS-CoV-2 has posed a serious threat to public health on a global scale. Given the current lack of an effective vaccine, several drugs have been repurposed for treatment and prophylaxis of COVID-19 in an attempt to find an effective cure.

Areas covered

The antimalarial drug hydroxychloroquine (HCQ) initially garnered widespread attention following the publication of preliminary results showing that this drug exerts an anti-SARS-CoV-2 activity in vitro.

Expert opinion

To date, clinical evidence suggests lack of benefit from HCQ use for the treatment of hospitalized patients with COVID-19. In such patients, HCQ also appears to be associated with an increased risk of QT interval prolongation and potentially lethal ventricular arrhythmias. Therefore, FDA has recently revoked the Emergency Use Authorization (EUA) for emergency use of HCQ and chloroquine to treat COVID-19. Conversely, whether HCQ use may represent an effective prophylactic strategy against COVID-19 is a separate question that still remains to be answered. In addition, relevant aspects regarding the potential risks and benefits of HCQ need to be clarified, in pursuit of a rational use of this drug in the COVID-19 pandemic era.

KEYWORDS:

• COVID-19
• drug repositioning
• hydroxychloroquine
• post-exposure prophylaxis
• pre-exposure prophylaxis
• prophylaxis
• remdesivir
• SARS-CoV-2
• treatment
• vitamin D

Article highlights

• Over the last few months, drug repositioning has allowed to investigate the off-label use of several drugs for prophylaxis and treatment of COVID-19, including the antimalarial drug hydroxychloroquine (HCQ).

• The postulated mechanisms of action by which HCQ may play an antiviral activity against SARS-CoV-2 include the potential HCQ ability to: i) inhibit viral binding to ACE2 receptor, membrane fusion and subsequent host cell entry by interfering with the terminal glycosylation of ACE2 and viral spike S protein, ii) inhibit the fusion between the viral envelope and lysosomal or endosomal membrane by increasing the pH within cytoplasmic acidic organelles, and iii) exert anti-inflammatory and immunomodulatory effects.

• Although preliminary studies showed that HCQ exerts an anti-SARS-CoV-2 activity in vitro, in vivo evidence for the efficacy of this drug as either prophylaxis or treatment of COVID-19 is lacking.

• To date, clinical evidence suggests lack of benefit from HCQ use in hospitalized patients with COVID-19. In such patients, HCQ also appears to be associated with an increased risk of QT interval prolongation and potentially lethal ventricular arrhythmias.

• On the other hand, the safety and efficacy of HCQ use as pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) for SARS-CoV-2 infection still remain to be established.

Acknowledgments

We would like to thank Mr. Enzo Luchetti (Studio Cyan, Via Beccari Odoardo 32, 00154 Rome, Italy) for his thorough work on creating the digital figure drawing.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was not funded.