Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19

Lucy C.K. Bell; Cem Meydan; Jacob Kim; Jonathan Foox; Daniel Butler; Christopher E. Mason; Sagi D. Shapira; Mahdad Noursadeghi; Gabriele Pollara

iScience (Jan 2021)

Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19

Lucy C.K. Bell,
Cem Meydan,
Jacob Kim,
Jonathan Foox,
Daniel Butler,
Christopher E. Mason,
Sagi D. Shapira,
Mahdad Noursadeghi,
Gabriele Pollara

Affiliations

Lucy C.K. Bell: Division of Infection & Immunity, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK; Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, UK
Cem Meydan: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
Jacob Kim: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
Jonathan Foox: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
Daniel Butler: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
Christopher E. Mason: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
Sagi D. Shapira: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
Mahdad Noursadeghi: Division of Infection & Immunity, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK; Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, UK
Gabriele Pollara: Division of Infection & Immunity, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK; Department of Infection, Royal Free London NHS Trust, London, UK; Corresponding author

Journal volume & issue: Vol. 24, no. 1
p. 101896

Abstract

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Summary: Dysregulated IL-1β 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-1β and IL-6 in COVID-19. We show that the expression of IL-1β 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-1β 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-1β 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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