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Baricitinib treatment resolves lower airway 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; 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 Yh; 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; Weiskopf, Daniela; Filev, Peter D; 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, Georgia, USA.
  • Pino M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Boddapati AK; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Viox EG; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Starke CE; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
  • Upadhyay AA; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Gumber S; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Busman-Sahay K; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Strongin Z; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
  • Harper JL; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Tharp GK; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Pellegrini KL; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Kirejczyk S; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Zandi K; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Tao S; Center for AIDS Research, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Horton TR; Center for AIDS Research, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Beagle EN; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Mahar EA; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Lee MY; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Cohen J; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Jean SM; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Wood JS; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Connor-Stroud F; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Stammen RL; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Delmas OM; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Wang S; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Cooney KA; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Sayegh MN; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Wang L; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Weiskopf D; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Filev PD; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Waggoner J; Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Piantadosi A; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Kasturi SP; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Al-Shakhshir H; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Ribeiro SP; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • Sekaly RP; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Levit RD; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Estes JD; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Vanderford TH; Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA.
  • Schinazi RF; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
  • Bosinger SE; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
  • Paiardini M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
bioRxiv ; 2020 Sep 16.
Article in English | MEDLINE | ID: covidwho-807103
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Year: 2020 Document Type: Article Affiliation country: 2020.09.16.300277

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Year: 2020 Document Type: Article Affiliation country: 2020.09.16.300277