Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients

Samir Awasthi, Tyler Wagner, A. J. Venkatakrishnan, Arjun Puranik, Matthew Hurchik, Vineet Agarwal, Ian Conrad, Christian Kirkup, Raman Arunachalam, John O’Horo, Walter Kremers, Rahul Kashyap, William Morice, John Halamka, Amy W. Williams, William Alvis Faubion, Andrew David Badley, Gregory J. Gores, Venky Soundararajan

Research output: Contribution to journalArticlepeer-review

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 better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential 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 BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.

Original languageEnglish (US)
Article number55
JournalCell Death Discovery
Volume7
Issue number1
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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