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
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.
