Project Team

E. John Wherry PhD: Professor and Chair, Department of Systems Pharmacology and Translational Therapeutics, Director Institute for Immunology, University of Pennsylvania

Mark Painter PhD: Postdoctoral fellow, Wherrylab. Expertise in human T cell biology and SARS-CoV-2 vaccine responses, University of Pennsylvania.

Michela Locci, PhD, Assistant Professor, Department of Microbiology, Perelman School of Medicine University of Pennsylvania

Benjamin Abramoff, MD, MS, Director of the Post-COVID Assessment and Recovery Clinic, Perelman School of Medicine University of Pennsylvania

Hannah Sharpe, PhD: Postdoctoral researcher and clinical coordinator, Perelman School of Medicine University of Pennsylvania

Diana Castano, PhD: Staff scientist, Perelman School of Medicine University of Pennsylvania

Project Summary:

Dr. Mark Painter is leading many of the Wherry lab’s T cell experiments

Extension of two LongCOVID studies focused on T cell biosensors and lymph node immune responses into second phases of research. The first study will expand to measure SARS-CoV-2-specific CD4 T cells and B cells in LongCOVID blood and tissue. The second will add more LongCOVID participants and additional sample collection timepoints to the study research design. Findings have the potential to guide LongCOVID biomarkers and therapeutics and to inform possible mechanisms of immune dysregulation behind other debilitating chronic conditions tied to infection.

Project background:

Features of the immune response can be used to infer the activity of pathogens such as SARS-CoV-2 and Epstein Barr virus in LongCOVID. Currently, two research teams at the University of Pennsylvania are using advanced technologies to determine if T cell activity and lymph node immune system responses can be used as biosensors or indicators of LongCOVID viral persistence. Dr. John Wherry, Dr. Mark Painter, and team are determining if CD8 T cells specific for SARS-CoV-2 proteins can be used as blood biosensors of viral persistence. They have already started to find evidence of ongoing activation of SARS-CoV-2 specific CD8 T cells in a subset of Long COVID patients. In a related project, Dr. Michela Locci and team are studying if LongCOVID is connected to altered immune responses in lymphoid tissue. They are using a Fine Needle Aspirate (FNA) biopsy procedure to collect lymph node tissue from LongCOVID patients to examine immune responses triggered by SARS-CoV-2 and Epstein-Barr virus. Early data indicates possible differences in LongCOVID lymph node immune responses, however expansion of the study to more participants and timepoints is needed to maximize signal. 

Early data from Dr. Wherry’s team showing increased spike-specific CD8 T cells in a subset of LongCOVID patients

Phase 2 expands both these studies in size and scope, helping the teams create extended blueprints of LongCOVID immune features. Dr. Wherry’s team is extending their antigen-specific immune cell biosensor study to include virus-specific CD4 T cells and virus-specific B cells. Analysis will be performed in blood, but also on LongCOVID intestinal and lymph node tissue samples collected via teams at UCSF and Mount Sinai. Dr. Locci’s team will add more patients and timepoints to the study design. This includes capturing more lymph node immune responses to Epstein-Barr virus in addition to SARS-CoV-2.