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Author Notes:

Conceptualization, T.N.H., M. Pino, J.L.H., G.S., A.P., S.E.B., R.F.S., and M. Paiardini; Methodology, T.N.H., M. Pino, A.K.B., E.G.V., N.K., K.B.-S., A.A.U., Z.S., G.K.T., K.L.P., S.G., S.K., S.T., O.M.D., K.A.C., M.N.S., L.W., P.D.F., J.W., A.P., S.P.K., C.E.S., S.W., H.A., E.A.M., M.Y.H.L., K.Z., S.T., T.R.H., E.N.B., S.P.R., and T.H.V.; Formal Analysis, T.N.H., M. Pino, Z.S., E.G.V., A.K.B., K.B.-S., A.A.U., G.K.T., S.G., S.K., S.T., P.D.F., J.W., A.P., S.P.K., S.P.R., and T.H.V; Investigation, T.N.H., M. Pino, E.G.V., J.C., S.M.J., J.S.W., F.C.-S., R.L.S., R.D.L., A.P., S.P.R., R.P.S., and T.H.V.; Resources, D.W., R.F.S., S.E.B., and M. Paiardini; Writing – Original Draft, T.N.H., M. Pino, J.L.H., and M. Paiardini; Writing – Review & Editing, T.N.H., M. Pino, J.L.H., S.E.B., and M. Paiardini; Visualization, T.N.H., M. Pino, A.K.B., A.A.U., G.K.T., Z.S., and E.G.V.; Supervision, R.F.S., S.E.B., and M. Paiardini; Funding Acquisition, A.P., S.E.B., R.F.S., and M. Paiardini.

We thank the Yerkes National Primate Research Center (YNPRC) Division of Animal Resources, especially Stephanie Ehnert, Stacey Weissman, Denise Bonenberger, John M. Wambua, Dominic M. D’Urso, Racquel Sampson-Harley, and Kalpana Patel in Research Resources for providing support in animal care. We thank Nichole Arnett for assistance with clinical pathology assays and Kevin Nguyen for additional laboratory processing. We thank Dr. Vincent Marconi for discussions and critical reading of the manuscript. Pharmaceutical-grade baricitinib was commercially obtained, provided free of charge by Dr. Schinazi, and it was found to be >99% pure by LC-MS-MS.

R.F.S. served as an unpaid consultant for Eli Lilly whose drugs are being evaluated in the research described in this paper. In addition, R.F.S. 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. Eli Lilly had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. All other authors do not have any conflicts to declare.

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Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • RIG-I
  • EXPRESSION
  • INFECTION
  • COVID-19
  • MILD
  • SARS

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

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Journal Title:

CELL

Volume:

Volume 184, Number 2

Publisher:

, Pages 460-+

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2020 Elsevier Inc.

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