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

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

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.