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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

Brandi N. Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle P. Porter, Jonathan Schulz, Neeltje van Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Pérez-Pérez, Atsushi Okumura, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Catharine M. Bosio, Sarah Anzick, Kent Barbian, Tomas Cihlar, Craig Martens, Dana P. Scott, View ORCID ProfileVincent J. Munster, Emmie de Wit
doi: https://doi.org/10.1101/2020.04.15.043166
Brandi N. Williamson
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Friederike Feldmann
2Rocky Mountain Veterinary Branch, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Benjamin Schwarz
3Laboratory of Bacteriology and Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Kimberly Meade-White
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Danielle P. Porter
5Gilead Sciences, Foster City, CA, United States of America
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Jonathan Schulz
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Neeltje van Doremalen
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Ian Leighton
3Laboratory of Bacteriology and Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Claude Kwe Yinda
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Lizzette Pérez-Pérez
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Atsushi Okumura
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Jamie Lovaglio
2Rocky Mountain Veterinary Branch, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Patrick W. Hanley
2Rocky Mountain Veterinary Branch, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Greg Saturday
2Rocky Mountain Veterinary Branch, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Catharine M. Bosio
3Laboratory of Bacteriology and Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Sarah Anzick
4Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Kent Barbian
4Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Tomas Cihlar
5Gilead Sciences, Foster City, CA, United States of America
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Craig Martens
4Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Dana P. Scott
2Rocky Mountain Veterinary Branch, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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Vincent J. Munster
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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  • ORCID record for Vincent J. Munster
Emmie de Wit
1Laboratory of Virology, Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America
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  • For correspondence: Emmie.dewit@nih.gov
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Abstract

Background Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection.

Methods To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy.

Results In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue.

Conclusions Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.

Competing Interest Statement

The authors affiliated with Gilead Sciences are employees of the company and own company stock. The authors affiliated with NIH have no conflict of interest to report.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted April 22, 2020.
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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
Brandi N. Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle P. Porter, Jonathan Schulz, Neeltje van Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Pérez-Pérez, Atsushi Okumura, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Catharine M. Bosio, Sarah Anzick, Kent Barbian, Tomas Cihlar, Craig Martens, Dana P. Scott, Vincent J. Munster, Emmie de Wit
bioRxiv 2020.04.15.043166; doi: https://doi.org/10.1101/2020.04.15.043166
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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
Brandi N. Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle P. Porter, Jonathan Schulz, Neeltje van Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Pérez-Pérez, Atsushi Okumura, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Catharine M. Bosio, Sarah Anzick, Kent Barbian, Tomas Cihlar, Craig Martens, Dana P. Scott, Vincent J. Munster, Emmie de Wit
bioRxiv 2020.04.15.043166; doi: https://doi.org/10.1101/2020.04.15.043166

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