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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
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 effe...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239049/ https://www.ncbi.nlm.nih.gov/pubmed/32511319 http://dx.doi.org/10.1101/2020.04.15.043166 |
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author | Williamson, Brandi N. Feldmann, Friederike Schwarz, Benjamin Meade-White, Kimberly Porter, Danielle P. Schulz, Jonathan van Doremalen, Neeltje Leighton, Ian Kwe Yinda, Claude Pérez-Pérez, Lizzette Okumura, Atsushi Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Bosio, Catharine M. Anzick, Sarah Barbian, Kent Cihlar, Tomas Martens, Craig Scott, Dana P. Munster, Vincent J. de Wit, Emmie |
author_facet | Williamson, Brandi N. Feldmann, Friederike Schwarz, Benjamin Meade-White, Kimberly Porter, Danielle P. Schulz, Jonathan van Doremalen, Neeltje Leighton, Ian Kwe Yinda, Claude Pérez-Pérez, Lizzette Okumura, Atsushi Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Bosio, Catharine M. Anzick, Sarah Barbian, Kent Cihlar, Tomas Martens, Craig Scott, Dana P. Munster, Vincent J. de Wit, Emmie |
author_sort | Williamson, Brandi N. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7239049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-72390492020-06-07 Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Williamson, Brandi N. Feldmann, Friederike Schwarz, Benjamin Meade-White, Kimberly Porter, Danielle P. Schulz, Jonathan van Doremalen, Neeltje Leighton, Ian Kwe Yinda, Claude Pérez-Pérez, Lizzette Okumura, Atsushi Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Bosio, Catharine M. Anzick, Sarah Barbian, Kent Cihlar, Tomas Martens, Craig Scott, Dana P. Munster, Vincent J. de Wit, Emmie bioRxiv Article 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. Cold Spring Harbor Laboratory 2020-04-22 /pmc/articles/PMC7239049/ /pubmed/32511319 http://dx.doi.org/10.1101/2020.04.15.043166 Text en https://creativecommons.org/publicdomain/zero/1.0/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 (https://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Article Williamson, Brandi N. Feldmann, Friederike Schwarz, Benjamin Meade-White, Kimberly Porter, Danielle P. Schulz, Jonathan van Doremalen, Neeltje Leighton, Ian Kwe Yinda, Claude Pérez-Pérez, Lizzette Okumura, Atsushi Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Bosio, Catharine M. Anzick, Sarah Barbian, Kent Cihlar, Tomas Martens, Craig Scott, Dana P. Munster, Vincent J. de Wit, Emmie Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title_full | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title_fullStr | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title_full_unstemmed | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title_short | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 |
title_sort | clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239049/ https://www.ncbi.nlm.nih.gov/pubmed/32511319 http://dx.doi.org/10.1101/2020.04.15.043166 |
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