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. 2021 Jul;22(10):1257-1266.
doi: 10.1080/14656566.2021.1898589. Epub 2021 Mar 16.

Does hydroxychloroquine still have any role in the COVID-19 pandemic?

William Hk Schilling  1   2 , Nicholas J White  1   2
Affiliations

Does hydroxychloroquine still have any role in the COVID-19 pandemic?

William Hk Schilling et al. Expert Opin Pharmacother. 2021 Jul.

Abstract

Introduction: The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic.Areas covered: Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed.Expert opinion: The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.

Keywords: COVID-19; Chloroquine; SARS-CoV-2; antiviral; hydroxychloroquine; pharmacokinetics; prevention.

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Figures

Figure 1.
Figure 1.
Meta-analysis of published hydroxychloroquine prevention studies showing a non-significant overall approximate 15% reduction in COVID-19 [5–8,11]
Figure 2.
Figure 2.
Simple synopsis of the natural history of COVID-19 infection. Peak viral burden occurs around the time of illness onset, whereas hospitalization and clinical deterioration occur later, when the viral burden has decreased and the downstream inflammation predominates
See this image and copyright information in PMC

References

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    2. • In-depth analysis of clinical pharmacology of chloroquine and hydroxychloroquine, with a review of toxicity evidence and pharmacokinetic modeling of dosing used in clinical trials in prevention and treatment.

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    2. • A well-conducted, randomized controlled trial published early in the pandemic which excluded very large benefits of hydroxychloroquine when given as post-exposure prophylaxis.