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

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.

• Authors: Kyle Rosenke, Michael A Jarvis, Friederike Feldmann, Benjamin Schwarz, Atsushi Okumura, Jamie Lovaglio, Greg Saturday, Patrick W Hanley, Kimberly Meade-White, Brandi N Williamson, Frederick Hansen, Lizette Perez-Perez, Shanna Leventhal, Tsing-Lee Tang-Huau, Julie Callison, Elaine Haddock, Kaitlin A Stromberg, Dana Scott, Graham Sewell, Catharine M Bosio, David Hawman, Emmie de Wit, Heinz Feldmann
• Journal: JCI insight (JCI Insight) Vol. 5 Issue 23 (12 03 2020) ISSN: 2379-3708 [Electronic] United States
• PMID: 33090972 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antiviral Agents
• Cytokines
• Hydroxychloroquine

Topics

• Animals
• Antiviral Agents (therapeutic use)
• COVID-19 (pathology, prevention & control, therapy)
• Chlorocebus aethiops
• Cricetinae
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Humans
• Hydroxychloroquine (therapeutic use)
• Lung (pathology, 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)
• COVID-19 Drug Treatment