DIKUL - logo
E-resources
Peer reviewed Open access
  • Baricitinib treatment resol...
    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

    Cell, 01/2021, Volume: 184, Issue: 2
    Journal Article

    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. Display omitted •SARS-CoV-2-infected RMs mimic signatures of inflammation seen in COVID-19 patients•Baricitinib suppresses production of pro-inflammatory cytokines in lung macrophages•Baricitinib limits recruitment of neutrophils to the lung and NETosis•Baricitinib preserves innate antiviral and SARS-CoV-2-specific T cell responses 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.