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Hydroxychloroquine prophylaxis and treatment is ineffective in macaque and hamster SARS-CoV-2 disease models
Kyle Rosenke, … , Emmie de Wit, Heinz Feldmann
Kyle Rosenke, … , Emmie de Wit, Heinz Feldmann
Published October 22, 2020
Citation Information: JCI Insight. 2020;5(23):e143174. https://doi.org/10.1172/jci.insight.143174.
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Research Article COVID-19 Therapeutics

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

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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 3

Rhesus macaque model — gross and histopathology.

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Rhesus macaque model — gross and histopathology.
Macaques were infected ...
Macaques were infected with SARS-CoV-2 as described in the legend of Figure 1. Animals were euthanized on day 7 after infection for gross pathology and histopathology. (A and B) Gross pathology with consolidated lower left lung lobe and area of postmortem BAL in the lower right lung lobe (asterisk). (C) H&E (original magnification, ×100) and IHC (original magnification, ×200). H&E staining in both the hydroxychloroquine and vehicle groups revealed multifocal, minimal-to-moderate, interstitial pneumonia frequently centered on terminal bronchioles. Alveolar edema and fibrin with formation of hyaline membranes were seen only in lungs with moderate changes. Multifocal perivascular infiltrates of small numbers of lymphocytes that form perivascular cuffs. Corresponding IHC showing immunopositivity in type I and II pneumocytes. Black measurement bars represent 50 μm for H&E and 20 μm for IHC figures. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; BAL, bronchoalveolar lavage; PS, prophylaxis; TS, treatment.

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