TY - JOUR
T1 - Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients
AU - Awasthi, Samir
AU - Wagner, Tyler
AU - Venkatakrishnan, A. J.
AU - Puranik, Arjun
AU - Hurchik, Matthew
AU - Agarwal, Vineet
AU - Conrad, Ian
AU - Kirkup, Christian
AU - Arunachalam, Raman
AU - O’Horo, John
AU - Kremers, Walter
AU - Kashyap, Rahul
AU - Morice, William
AU - Halamka, John
AU - Williams, Amy W.
AU - Faubion, William A.
AU - Badley, Andrew D.
AU - Gores, Gregory J.
AU - Soundararajan, Venky
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
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U2 - 10.1038/s41420-021-00429-9
DO - 10.1038/s41420-021-00429-9
M3 - Article
AN - SCOPUS:85102578995
SN - 2058-7716
VL - 7
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 55
ER -