Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

• Type of Material: Article
• Authors: Timothy N. Hoang, Emory University; Maria Pino, Emory University; Arun K. Boddapati, Emory University; Elise G. Viox, Emory University; Carly E. Starke, Oregon Health and Science University; Amit Upadhyay, Emory University; Sanjeev Gumber, Emory University; Michael Nekorchuk, Oregon Health and Science University; Kathleen Busman-Sahay, Oregon Health and Science University; Zachary Strongin, Emory University; Justin L. Harper, Emory University; Gregory K. Tharp, Emory University; Kathryn L. Pellegrini, Emory University; Shannon Kirejczyk, Emory University; Keivan Zandi, Emory University; Sijia Tao, Emory University; Tristan R. Horton, Emory University; Elizabeth N. Beagle, Emory University; Ernestine A. Mahar, Emory University; Michelle Y.H. Lee, Emory University; Joyce Cohen, Emory University; Sherrie Jean, Emory University; Jennifer Wood, Emory University; Fawn Connor-Stroud, Emory University; Rachelle Stammen, Emory University; Olivia M. Delmas, Emory University; Shelly Wang, Emory University; Kimberly A. Cooney, Emory University; Michael N. Sayegh, Emory University; Lanfang Wang, Emory University; Peter Filev, Emory University; Daniela Weiskopf, La Jolla Institute for Allergy and Immunology; Guido Silvestri, Emory University; Jesse Waggoner, Emory University; Anne Piantadosi, Emory University; Sudhir Kasturi, Emory University; Hilmi Al-Shakhshir, Case Western Reserve University; Susan P. Ribeiro, Emory University; Rafick-Pierre Sekaly, Emory University; Rebecca Levit, Emory University; Jacob D. Estes, Oregon Health and Science University; Thomas Vanderford, Emory University; Raymond Schinazi, Emory University; Steven Bosinger, Emory University; Mirko Paiardini, Emory University
• Language: English
• Date: 2021-01-21
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2020.11.007
• Title of Journal or Parent Work: CELL
• Volume: 184
• Issue: 2
• Start Page: 460
• End Page: +
• Grant/Funding Information: This study was supported by an Emory University COVID-19 Molecules and Pathogens to Populations and Pandemics Initiative Seed Grant to M. Paiardini, A.P., and R.F.S.; by YNPRC Coronavirus Pilot Research Project Program grant to M. Paiardini under award P51 OD11132; and by Fast Grants Award #2144 to M. Paiardini. This work was additionally funded by the National Institute of Allergy and Infectious Diseases (NIAID, NIH) under awards R37AI141258 and R01AI116379 to M. Paiardini, R01MH116695 to R.F.S, R01AI143411, R01HL140223 to R.D.L., and R01AI149672 to J.D.E., and U24AI120134 to S.E.B. Support for this work was also provided by award NIH Office of Research Infrastructure Programs (ORIP) P51OD11132 to YNPRC, P51OD011092 to ONPRC, 1S10OD025002-01 to the Integrated Pathology Core/ONPRC, NIAID award P30 AI050409 to the Center for AIDS Research (CFAR) at Emory University, and contract Nr. 75N9301900065 (to D.W.). Next-generation sequencing services were provided by the Yerkes NHP Genomics Core, which is supported in part by NIH P51OD011132. Sequencing data were acquired on an Illumina NovaSeq6000 funded by NIH S10OD026799 to S.E.B. Pictorial illustrations were created with BioRender.com. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services nor does it imply endorsement of organizations or commercial products.
• Keywords: INFECTION; RIG-I; Life Sciences & Biomedicine; SARS; Biochemistry & Molecular Biology; Science & Technology; MILD; EXPRESSION; COVID-19; Cell Biology
• Research Categories: Biology, Cell; Biology, Molecular; Chemistry, Biochemistry

Abstract

Using a rhesus macaque infection model, it is shown that baricitinib treatment started early after infection effectively resolves inflammatory signatures in airway macrophages, with decreased lung pathology and neutrophil infiltration.