Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Nature. 2020 Sep;585(7826):584-587. doi: 10.1038/s41586-020-2558-4. Epub 2020 Jul 22.

Abstract

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azithromycin / pharmacology
  • Azithromycin / therapeutic use
  • Betacoronavirus / drug effects*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / physiopathology
  • Coronavirus Infections / virology*
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Humans
  • Hydroxychloroquine / pharmacokinetics
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use*
  • In Vitro Techniques
  • Kinetics
  • Macaca fascicularis
  • Male
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / physiopathology
  • Pneumonia, Viral / virology*
  • Pre-Exposure Prophylaxis
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / virology
  • SARS-CoV-2
  • Time Factors
  • Treatment Failure
  • Vero Cells
  • Viral Load / drug effects

Substances

  • Cytokines
  • Hydroxychloroquine
  • Azithromycin

Supplementary concepts

  • COVID-19 drug treatment