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Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques
Open accessPublished version of a preprint
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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“suppressed the production of proinflammatory cytokines in lung macrophages, and the recruitment of neutrophils to the lung (Hoang et al., 2021).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Hoang et al., 2021
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Metadata
- Authors
- Hoang, T. N., Pino, M., Boddapati, A. K., Viox, E. G., Starke, C. E., Upadhyay, A. A., Gumber, S., Nekorchuk, M., Busman-Sahay, K., Strongin, Z., Harper, J. L., Tharp, G. K., Pellegrini, K. L., Kirejczyk, S., Zandi, K., Tao, S., Horton, T. R., Beagle, E. N., Mahar, E. A., Lee, M. Y. H., Cohen, J., Jean, S. M., Wood, J. S., Connor-Stroud, F., Stammen, R. L., Delmas, O. M., Wang, S., Cooney, K. A., Sayegh, M. N., Wang, L., Filev, P. D., Weiskopf, D., Silvestri, G., Waggoner, J., Piantadosi, A., Kasturi, S. P., Al-Shakhshir, H., Ribeiro, S. P., Sekaly, R. P., Levit, R. D., Estes, J. D., Vanderford, T. H., Schinazi, R. F., Bosinger, S. E., & Paiardini, M.
- Affiliations
- Emory University (US)
- Oregon Health & Science University (US)
- La Jolla Institute for Immunology (US)
- Case Western Reserve University (US)
- Oregon National Primate Research Center (US)
- Corresponding author
- Schinazi, Raymond F.
- Bosinger, Steven E.
- Paiardini, Mirko
- ORCID
- Hoang, Timothy N.
- Boddapati, Arun K.
- Viox, Elise G.
- Starke, Carly E.
- Upadhyay, Amit A.
- Gumber, Sanjeev
- Harper, Justin L.
- Tharp, Gregory K.
- Pellegrini, Kathryn L.
- Kirejczyk, Shannon
- Zandi, Keivan
- Mahar, Ernestine A.
- Lee, Michelle Y.H.
- Cohen, Joyce
- Jean, Sherrie M.
- Wood, Jennifer S.
- Connor-Stroud, Fawn
- Stammen, Rachelle L.
- Wang, Shelly
- Sayegh, Michael N.
- Wang, Lanfang
- Weiskopf, Daniela
- Silvestri, Guido
- Waggoner, Jesse
- Piantadosi, Anne
- Kasturi, Sudhir P.
- Al-Shakhshir, Hilmi
- Ribeiro, Susan P.
- Levit, Rebecca D.
- Estes, Jacob D.
- Vanderford, Thomas H.
- Schinazi, Raymond F.
- Bosinger, Steven E.
- Paiardini, Mirko
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 184
- Issue
- 2
- Pages
- 460-475.e21
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7654323
- OpenAlex
- W3101403202
- Cited by
- 212
- References
- 62
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 26 · 2023: 33 · 2022: 57 · 2021: 66
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Office of Research Infrastructure Programs, National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- baricitinib, SARS-CoV-2, COVID-19 pandemic, JAK1/2 inhibitor, lung macrophages, neutrophil recruitment, NETosis, cytokine storm, lung inflammation, rhesus macaque model, viral shedding, type I interferon, SARS-CoV-2-specific T cells, cytokine and chemokine production
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