Journal
ISCIENCE
Volume 24, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.101896
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Funding
- Wellcome Trust [207511/Z/17/Z, WT101766/Z/13/Z]
- Clinical Lectureship and Clinical Fellowship - National Institute for Health Research (NIHR)
- National Institutes of Health [5R01GM109018, 5U54CA209997, R21AI129851, R01MH117406, R01AI151059]
- Starr Cancer Consortium [I13-0052]
- WorldQuant Foundation
- Pershing Square Sohn Cancer Research Alliance
- NASA [NNX14AH50G, NNX17AB26G]
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The expression of IL-1 beta and IL-6 response modules can provide a dynamic readout of functional cytokine activity in vivo in COVID-19, without being associated with disease severity or mortality.
Dysregulated IL-1 beta 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-1 beta and IL-6 in COVID-19. We show that the expression of IL-1 beta 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-1 beta 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-1 beta 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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