Plasma IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients
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- July 19 2020
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- July 19 2020
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: Venky Soundararajan (venky@nference.net)
- Correspondence:
- Venky Soundararajan (venky@nference.net)