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| Status |
Public on Nov 10, 2020 |
| Title |
Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques [RNA-Seq] |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SARS-CoV-2 induced hypercytokinemia and inflammation are critically associated with COVID-19 disease severity. Baricitinib, a clinically approved JAK1/2 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 IFN antiviral responses and SARS-CoV-2-specific T-cell responses remained similar between the two groups. Importantly, animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of neutrophils, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of lung macrophages 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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| Overall design |
Eight rhesus macaques (Macaca mulatta) were infected with SARS-CoV-2. Four RMs were administered 4 mg Baricitinib starting at day 2 post-infection (DPI) for 8-9 consecutive days. RNA-Seq profiling of cells isolated from BAL (bronchoalveolar lavages) prior to SARS-CoV-2 inoculation (-5 DPI; Baseline); 2 days after virus inoculation, prior to baricitinib treatment (2 DPI); and 4 days after infection, and 48 hours after beginning baricitinib (4 DPI).
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| Contributor(s) |
Hoang TN, Pino M, Boddapati AK, Viox EG, Starke CE, Upadhyay AA, Gumber S, Nekorchuk M, Busman-Sahay K, Strongin Z, Harper JL, Tharp GK, Pellegrini KL, Kirejczyk S, Zandi K, Tao S, Horton TR, Beagle EN, Mahar EA, Lee MY, Cohen J, Jean SM, Wood JS, Connor-Stroud F, Stammen RL, Delmas OM, Wang S, Cooney KA, Sayegh MN, Wang L, Weiskopf D, Filev PD, Waggoner J, Piantadosi A, Kasturi SP, Al-Shakhshir H, Ribeiro SP, Sekaly RP, Levit RD, Estes JD, Vanderford TH, Schinazi RF, Bosinger SE, Paiardini M |
| Citation(s) |
33278358 |
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| Submission date |
Oct 07, 2020 |
| Last update date |
Dec 09, 2020 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
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| Phone |
404-727-7797
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| Organization name |
Yerkes National Primate Research Center
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| Department |
Developmental and Cognitive Neuroscience
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| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (1) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE159214 |
Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques |
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| Relations |
| BioProject |
PRJNA667960 |
| SRA |
SRP286686 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159213_BAL_counts.txt.gz |
734.6 Kb |
(ftp)(http) |
TXT |
| GSE159213_BAL_norm_counts.txt.gz |
2.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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