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Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques.
Hoang, Timothy N; Pino, Maria; Boddapati, Arun K; Viox, Elise G; Starke, Carly E; Upadhyay, Amit A; Gumber, Sanjeev; Nekorchuk, Michael; Busman-Sahay, Kathleen; Strongin, Zachary; Harper, Justin L; Tharp, Gregory K; Pellegrini, Kathryn L; Kirejczyk, Shannon; Zandi, Keivan; Tao, Sijia; Horton, Tristan R; Beagle, Elizabeth N; Mahar, Ernestine A; Lee, Michelle Y H; Cohen, Joyce; Jean, Sherrie M; Wood, Jennifer S; Connor-Stroud, Fawn; Stammen, Rachelle L; Delmas, Olivia M; Wang, Shelly; Cooney, Kimberly A; Sayegh, Michael N; Wang, Lanfang; Filev, Peter D; Weiskopf, Daniela; Silvestri, Guido; Waggoner, Jesse; Piantadosi, Anne; Kasturi, Sudhir P; Al-Shakhshir, Hilmi; Ribeiro, Susan P; Sekaly, Rafick P; Levit, Rebecca D; Estes, Jacob D; Vanderford, Thomas H; Schinazi, Raymond F; Bosinger, Steven E; Paiardini, Mirko.
  • Hoang TN; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Pino M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Boddapati AK; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Viox EG; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Starke CE; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Upadhyay AA; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Gumber S; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Nekorchuk M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Busman-Sahay K; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Strongin Z; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Harper JL; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Tharp GK; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Pellegrini KL; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Kirejczyk S; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Zandi K; Center for AIDS Research, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Tao S; Center for AIDS Research, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Horton TR; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Beagle EN; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Mahar EA; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Lee MYH; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Cohen J; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Jean SM; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Wood JS; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Connor-Stroud F; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Stammen RL; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Delmas OM; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Wang S; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Cooney KA; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Sayegh MN; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Wang L; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Filev PD; Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Weiskopf D; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Silvestri G; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Waggoner J; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Piantadosi A; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Kasturi SP; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Al-Shakhshir H; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Ribeiro SP; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Sekaly RP; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Levit RD; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Estes JD; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Vanderford TH; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Schinazi RF; Center for AIDS Research, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: rschina@emory.edu.
  • Bosinger SE; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, School of M
  • Paiardini M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: mirko.paiardini@emory.edu.
Cell ; 184(2): 460-475.e21, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-917237
ABSTRACT
SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. 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 interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage 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 inflammation induced by SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Purines / Pyrazoles / Sulfonamides / Azetidines / Neutrophil Infiltration / COVID-19 / COVID-19 Drug Treatment / Macaca mulatta / Anti-Inflammatory Agents Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Animals Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2020.11.007

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Purines / Pyrazoles / Sulfonamides / Azetidines / Neutrophil Infiltration / COVID-19 / COVID-19 Drug Treatment / Macaca mulatta / Anti-Inflammatory Agents Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Animals Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2020.11.007