Hydroxychloroquine prophylaxis and treatment is ineffective in macaque and hamster SARS-CoV-2 disease models

JCI Insight. 2020 Dec 3;5(23):e143174. doi: 10.1172/jci.insight.143174.

Abstract

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human COVID-19 clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies to help guide decisions. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in 2 animal disease models. The standard human malaria HCQ prophylaxis (6.5 mg/kg given weekly) and treatment (6.5 mg/kg given daily) did not significantly benefit clinical outcome, nor did it reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. Similarly, when used for prophylaxis or treatment, neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Results from these 2 preclinical animal models may prove helpful in guiding clinical use of HCQ for prophylaxis/treatment of COVID-19.

Keywords: COVID-19; Cytokines; Drug screens; Molecular biology; Therapeutics.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • COVID-19 / pathology
  • COVID-19 / prevention & control
  • COVID-19 / therapy*
  • COVID-19 Drug Treatment
  • Chlorocebus aethiops
  • Cricetinae
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Lung / pathology
  • Lung / virology
  • Macaca mulatta
  • Male
  • SARS-CoV-2 / drug effects*
  • Treatment Outcome
  • Vero Cells
  • Viral Load / drug effects
  • Virus Replication / drug effects
  • Virus Shedding / drug effects

Substances

  • Antiviral Agents
  • Cytokines
  • Hydroxychloroquine