Hydroxychloroquine prophylaxis and treatment is ineffective in macaque and hamster SARS-CoV-2 disease models
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
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
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Research Article COVID-19 Therapeutics

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

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Figure 4

Rhesus macaque model — viral loads in respiratory tissues.

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Rhesus macaque model — viral loads in respiratory tissues. Macaques were...
Macaques were infected with SARS-CoV-2 as described in the legend of Figure 1. Animals were euthanized on day 7 after infection for viral tissue load determination performed by qRT-PCR (subgenomic copies) and virus isolation (infectious virus). (A) Viral loads in lower and upper respiratory tissues and mediastinal lymph nodes for the prophylaxis study arm (PS). Virus isolation is indicated in numbers on top (n/5). (B) Viral lung loads (PS). All lung lobe genome copy data were combined. (C) Viral loads in lower and upper respiratory tissues and mediastinal lymph nodes for the treatment study arm (TS). Virus isolation frequency (number of animals per group) is indicated at top (n/5). (D) Viral lung loads (TS). All lung lobe genome copy data were combined. No statistical significance was found among groups presented in parts A–D. A linear model was used to analyze viral RNA levels in tissues and lung lobes. No significant difference was found between groups in either study. Red squares indicate vehicle-treated animals and blue circles indicate HCQ-treated animals. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; qRT-PCR, quantitative reverse transcriptase PCR; HCQ, hydroxychloroquine; PS, prophylaxis; TS, treatment.