RT Journal Article
SR Electronic
T1 Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.16.300277
DO 10.1101/2020.09.16.300277
A1 Timothy N. Hoang
A1 Maria Pino
A1 Arun K. Boddapati
A1 Elise G. Viox
A1 Carly E. Starke
A1 Amit A. Upadhyay
A1 Sanjeev Gumber
A1 Kathleen Busman-Sahay
A1 Zachary Strongin
A1 Justin L. Harper
A1 Gregory K. Tharp
A1 Kathryn L. Pellegrini
A1 Shannon Kirejczyk
A1 Keivan Zandi
A1 Sijia Tao
A1 Tristan R. Horton
A1 Elizabeth N. Beagle
A1 Ernestine A. Mahar
A1 Michelle YH Lee
A1 Joyce Cohen
A1 Sherrie M. Jean
A1 Jennifer S. Wood
A1 Fawn Connor-Stroud
A1 Rachelle L. Stammen
A1 Olivia M. Delmas
A1 Shelly Wang
A1 Kimberly A. Cooney
A1 Michael N. Sayegh
A1 Lanfang Wang
A1 Daniela Weiskopf
A1 Peter D. Filev
A1 Jesse Waggoner
A1 Anne Piantadosi
A1 Sudhir P. Kasturi
A1 Hilmi Al- Shakhshir
A1 Susan P. Ribeiro
A1 Rafick P. Sekaly
A1 Rebecca D. Levit
A1 Jacob D. Estes
A1 Thomas H. Vanderford
A1 Raymond F. Schinazi
A1 Steven E. Bosinger
A1 Mirko Paiardini
YR 2020
UL http://biorxiv.org/content/early/2020/09/16/2020.09.16.300277.abstract
AB Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.Competing Interest StatementDr. Raymond Schinazi served as an unpaid consultant for Eli Lilly whose drugs are being evaluated in the research described in this paper. In addition, Dr. Schinazi owns shares in Eli Lilly. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. All other authors do not have any conflicts to declare.