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Transcriptional response modules characterize IL-1ß and IL-6 activity in COVID-19.
Bell, Lucy C K; Meydan, Cem; Kim, Jacob; Foox, Jonathan; Butler, Daniel; Mason, Christopher E; Shapira, Sagi D; Noursadeghi, Mahdad; Pollara, Gabriele.
  • Bell LCK; Division of Infection & Immunity, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK.
  • Meydan C; Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, UK.
  • Kim J; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
  • Foox J; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
  • Butler D; Department of Systems Biology, Columbia University, New York, NY, USA.
  • Mason CE; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
  • Shapira SD; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
  • Noursadeghi M; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
  • Pollara G; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
iScience ; 24(1): 101896, 2021 Jan 22.
Article in English | MEDLINE | ID: covidwho-1129049
Preprint
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ABSTRACT
Dysregulated IL-1ß and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1ß and IL-6 in COVID-19. We show that the expression of IL-1ß or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1ß and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood but is not associated with severity of COVID-19 disease, length of stay, or mortality. We propose that IL-1ß and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo, aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2020.101896

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2020.101896