Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19

Postgrad Med. 2020 Sep;132(7):604-613. doi: 10.1080/00325481.2020.1778982. Epub 2020 Jun 21.

Abstract

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. Antiviral therapy is the most important treatment for COVID-19. Among the drugs under investigation, anti-malarials, chloroquine (CQ) and hydroxychloroquine (HCQ), are being repurposed as treatment for COVID-19. CQ/HCQ were shown to prevent receptor recognition by coronaviruses, inhibit endosome acidification, which interferes with membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies revealed inhibitory effects of CQ/HCQ on various coronaviruses, including SARS-CoV-2 although conflicting results exist. Several clinical studies showed that CQ/HCQ alone or in combination with a macrolide may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay disease progression, with less serious adverse effects. However, recent studies indicated that the use of CQ/HCQ, alone or in combination with a macrolide, did not show any favorable effect on patients with COVID-19. Adverse effects, including prolonged QT interval after taking CQ/HCQ, may develop in COVID-19 patients. Therefore, current data are not sufficient enough to support the use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken about the application of CQ/HCQ in COVID-19 before conclusive findings are obtained by well-designed, multi-center, randomized, controlled studies.

Keywords: Coronavirus; antiviral; chloroquine; hydroxychloroquine; sars-CoV-2.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects
  • Betacoronavirus / metabolism
  • COVID-19
  • COVID-19 Drug Treatment
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use*
  • Coronavirus 229E, Human / drug effects
  • Coronavirus Infections / drug therapy*
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Glycosylation
  • Humans
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use*
  • Immunity, Innate
  • In Vitro Techniques
  • Long QT Syndrome / chemically induced
  • Lymphocyte Activation / drug effects
  • MAP Kinase Signaling System
  • Middle East Respiratory Syndrome Coronavirus / drug effects
  • Pandemics
  • Peptidyl-Dipeptidase A / drug effects
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / drug therapy*
  • Reactive Oxygen Species
  • SARS-CoV-2
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Signal Transduction
  • T-Lymphocytes
  • Toll-Like Receptors / drug effects
  • Toll-Like Receptors / metabolism
  • Treatment Outcome
  • Virus Internalization / drug effects

Substances

  • Antiviral Agents
  • Cytokines
  • Reactive Oxygen Species
  • Toll-Like Receptors
  • Hydroxychloroquine
  • Chloroquine
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

This manuscript received no funding.