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Cell,11月9日,Baricitinib treatment resolves lower airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

编译者:zhangmin发布时间:Nov 18, 2020点击量:20296 来源栏目:最新研究

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

Timothy N. Hoang 13

Maria Pino 13

Arun K. Boddapati 13

Raymond F. Schinazi 14

Steven E. Bosinger 14

Mirko Paiardini 14, 15

Published:November 09, 2020DOI:https://doi.org/10.1016/j.cell.2020.11.007

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. 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 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 inflammation induced by SARS-CoV-2 infection.

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