nference

Plasma IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients

Abstract: Intensive Care Unit (ICU) admissions and mortality in severe COVID-19 patients are driven by “cytokine storms” and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays superior 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. Among 16 patients with plasma IL-6 measurement post-corticosteroid administration, a higher proportion of patients with an IL-6 value over 10 pg/mL have worse outcomes (i.e. ICU Length of Stay > 15 days or death) when compared to 41 patients treated with non-corticosteroid drugs including antivirals, tocilizumab, azithromycin, and hydroxychloroquine (p-value = 0.0024). Given this unexpected clinical association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the Glucocorticoid Receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single cell RNA-seq data from bronchoalveolar lavage fluid of severe COVID-19 patients and nearly 2 million human cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express both NR3C1 and IL-6. The mechanism of Glucocorticoid Receptor (GR) agonists mitigating pulmonary and multi-organ inflammation in some COVID-19 patients with respiratory failure, may be in part due to their successful antagonism of IL-6 production within lung macrophages and vasculature.

  • Authors:
  • Samir Awasthi1+,
  • Tyler Wagner1+,
  • AJ Venkatakrishnan1,
  • Arjun Puranik1,
  • Matthew Hurchik1,
  • Vineet Agarwal1,
  • Ian Conrad1,
  • Christian Kirkup1,
  • Raman Arunachalam2,
  • John O'Horo3,
  • Walter Kremers3,
  • Rahul Kashyap3,
  • William Morice, II3,4,
  • John Halamka3,5,
  • Amy W. Williams3,
  • William A. Faubion Jr.sup>3,
  • Andrew D. Badley3,
  • Gregory J. Gores3,
  • Venky Soundararajan1*
  • 1nference, Cambridge, MA, 02142, USA
  • 2nference Labs, Bangalore, India
  • 3Mayo Clinic, Rochester, MN 55905, USA
  • 4Mayo Clinic Laboratories, Rochester, MN 55905, USA
  • 5Mayo Clinic Platform, Rochester, MN 55905, USA
  • + Joint First Authors
  • Correspondence:
  • Affiliations:
  • Copyright:
  • The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
  • Affiliations:
  • Copyright:
  • The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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