RhRemdesivirSARSCoV2CompiledDataUpdated20200521.xlsx (34.97 kB)

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

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posted on 21.05.2020 by Brandi Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle Porter, Jonathan Schulz, Neeltje van Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Perez-Perez, Atsushi Okumura, Jamie Lovaglio, Patrick Hanley, Greg Saturday, Catharine Bosio, Sarah Anzick, Kent Barbian, Tomas Cihlar, Craig Martens, Dana Scott, Vincent J. Munster, Emmie de Wit

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.

Dataset supports publication:
Williamson, B.N., Feldmann, F., Schwarz, B. et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature (2020). https://doi.org/10.1038/s41586-020-2423-5

Also previously shared on bioRxiv: https://doi.org/10.1101/2020.04.15.043166

Funding

Intramural Research Program, National Institute of Allergy and Infectious Diseases (NIAID), NIH

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