Carrie Rosenberger, Ph.D.
Principal Scientist, Biomarker Discovery, Genentech, Inc.
A myeloid signature associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling
Severe viral and bacterial infections, including SARS-CoV-2, can trigger maladaptive inflammation and lung injury in some patients, leading to acute respiratory distress syndrome (ARDS) with a 30% mortality rate. COVID-19 presented an opportunity to test new therapies that may reduce disease progression from pneumonia to ARDS. Our reverse translation strategy aims to identify new targetable pathways by analyzing clinical samples to define patient subgroups that vary in disease progression or treatment response. As an example of our approach, we’ve identified a myeloid state in airway samples that is associated with severity in COVID-19 and ARDS and is driven by IL-6. This altered myeloid state is characterized by features of suppressor cell functionality, with low antigen presentation capacity and high expression of T cell-suppressive factors such as PD-L1 and IL-10. Blockade of IL-6 signaling by Anti-IL6R in a placebo-controlled clinical trial rapidly normalizes myeloid and T cell transcriptional states. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in pneumonia caused by other pathogens. We are using single cell RNA-seq, proteomics, and genetic data from patient cohorts to develop strategies to target maladaptive inflammation and defining biomarkers to identify which ARDS patients have the greatest potential to benefit from novel drugs.
Zoom Meeting: 5-6pm (members will receive a separate email with link information)
UPCOMING EPAASM Events 2022
793rd March 28th, 2022: Russell Vance, UC Berkeley, 5-6pm
794th April 25th, 2022: Bobbi Pritt, Mayo Clinic, 5-6pm
795th May 23rd, 2022: Student speakers at 4-5pm, Invited Speaker 5-6pm (Student Comm)
796th June 13th, 2022 Norman Willett Memorial Lecture: Invited Speaker 5-6pm (Education Comm)
EPAASM YouTube Channel (video recording of this lecture is not available)