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Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment.
Clin Immunol. 2020 09; 218:108517.CI

Abstract

Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19.

Authors+Show Affiliations

Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: Yeleswaram@incyte.com.Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: PSmith@incyte.com.Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: TBurn@incyte.com.Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: MCovington@incyte.com.Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: ajuvekar@incyte.com.Incyte Research Institute, Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: YLi@incyte.com.Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: MSquier@incyte.com.Incyte Corporation, 1801 Augustine Road, Wilmington, DE 19803, USA. Electronic address: plangmuir@incyte.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32585295

Citation

Yeleswaram, Swamy, et al. "Inhibition of Cytokine Signaling By Ruxolitinib and Implications for COVID-19 Treatment." Clinical Immunology (Orlando, Fla.), vol. 218, 2020, p. 108517.
Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol. 2020;218:108517.
Yeleswaram, S., Smith, P., Burn, T., Covington, M., Juvekar, A., Li, Y., Squier, P., & Langmuir, P. (2020). Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clinical Immunology (Orlando, Fla.), 218, 108517. https://doi.org/10.1016/j.clim.2020.108517
Yeleswaram S, et al. Inhibition of Cytokine Signaling By Ruxolitinib and Implications for COVID-19 Treatment. Clin Immunol. 2020;218:108517. PubMed PMID: 32585295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. AU - Yeleswaram,Swamy, AU - Smith,Paul, AU - Burn,Timothy, AU - Covington,Maryanne, AU - Juvekar,Ashish, AU - Li,Yanlong, AU - Squier,Peg, AU - Langmuir,Peter, Y1 - 2020/06/23/ PY - 2020/05/15/received PY - 2020/06/16/revised PY - 2020/06/17/accepted PY - 2020/6/26/pubmed PY - 2020/8/26/medline PY - 2020/6/26/entrez KW - COVID-19 KW - Coronavirus KW - Cytokine storm KW - Janus kinase KW - Ruxolitinib SP - 108517 EP - 108517 JF - Clinical immunology (Orlando, Fla.) JO - Clin Immunol VL - 218 N2 - Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19. SN - 1521-7035 UR - https://www.unboundmedicine.com/medline/citation/32585295/Inhibition_of_cytokine_signaling_by_ruxolitinib_and_implications_for_COVID_19_treatment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(20)30397-1 DB - PRIME DP - Unbound Medicine ER -