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bioRxiv · 10.1101/2020.07.22.202275

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

Bell, L. C. K.·Noursadeghi, M.·Pollara, G.
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Abstract

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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Bell, L. C. K., Noursadeghi, M., Pollara, G.. 2020-07-23. Transcriptional response modules characterise IL-1 and IL-6 activity in COVID-19. https://doi.org/10.1101/2020.07.22.202275

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