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.org

EPAASM YouTube Channel (video recording of this lecture is not available)

Twitter: @EPAASMBranch

Please join us for the monthly meeting on January 24th, 2022 

Rebekah E. Dumm, PhD

CPEP Fellow in Medical and Public Health Microbiology

Hospital of the University of Pennsylvania and

Children’s Hospital of Philadelphia 

Clinical Utility of Broad-Range 16S rRNA gene PCR with Sequencing

Broad-range bacterial 16S rRNA gene PCR with sequencing (BRPS) is used to detect bacterial pathogens present in clinical specimens. BRPS has demonstrated utility in identifying the causative agent, particularly from normally sterile sites with high suspicion of infection, even when cultures are negative. The goal of this study was to review the experience at the Hospital of the University of Pennsylvania (HUP) with send-out testing to reference laboratories for BRPS, evaluating ways to improve clinical utilization of the test. This was accomplished by correlating the BRPS results with microbiology cultures and surgical pathology findings and using these features to predict high-yield samples and specimen types. This talk will also discuss optimal use cases and highlight some practical interventions for improving patient care through diagnostic stewardship.

Lecture 5 to 6pm

Zoom Meeting link will be emailed to Branch members

Watch Dr Dumm’s lecture on our YouTube Channel : https://m.youtube.com/watch?v=JxpB51xfmI4

The Eastern PA Branch of the ASM will host the 50th Annual Symposium on Friday, November 5, 2021

“50 Year Historic Look-back and the View Ahead for Novel Diagnostics”

Preliminary Program

Moderator: Alan Evangelista, Ph.D., D(ABMM)

8:30-9:00am “50-year historic lookback at previous EPAASM symposia”, James Poupard, Ph.D., Pharma Institute of Philadelphia

9:00-9:30am “An update on the use of sepsis biomarkers including procalcitonin, C-reactive protein, and calprotectin”, Kevin J. Downes, M.D., Children’s Hospital of Philadelphia

9:30-10:00am “Progression of blood culture technology: automation, direct disk testing, PCR of positives and direct molecular sequencing of blood”, Thomas Kirn, M.D., Ph.D., Rutgers Robert Wood Johnson Medical School

Moderator: Matthew Pettengill, Ph.D., D(ABMM)

11:15-12:00pm Case presentations using molecular diagnostics, Matthew Pettengill, Ph.D., Thomas Jefferson Univ Hospital, Laurel Glaser, M.D., Ph.D., Hospital of the Univ of Pennsylvania, Alan Evangelista, Ph.D., St. Christopher’s Hospital for Children.

12:00-12:30pm Use of direct next generation sequencing for detection of clinical pathogens”, Erin H. Graf, Ph.D., D(ABMM), Mayo Clinic Arizona

12:30-1:45pm Lunch Break and Virtual Exhibit Breakout Rooms

Moderator: Laurel Glaser, M.D., Ph.D., D(ABMM)

1:45-2:15pm “Use of CSF metagenomic next generation sequencing (NGS) for direct pathogen detection for meningitis/encephalitis”, Kyle Rodino, Ph.D., D(ABMM), Hospital of the University of Pennsylvania

2:15-2:45pm “Evolving epidemiology of SARS-CoV-2 variants and their impact on patient outcomes, Brendan Kelly, M.D., Perelman Sch of Medicine, Univ of Pennsylvania

2:45-3:15pm “Use of artificial intelligence (AI) in the clinical microbiology laboratory”, Daniel Rhoads, M.D., Cleveland Clinic

3:15-3:30pm Closing remarks and evaluations

Virtual Exhibits by various vendors
Pre-registration by October 29, 2021: $50.00 members, $75.00 non-members
Full-registration after October 29, 2021: $75.00 members, $100.00 non-members

Register for the Meeting – click here

Program Brochure

P.S. Video recordings of the symposium will be available to all registered for the symposium approximately 1 month after the meeting