PHILADELPHIA-The University of Pennsylvania Perelman School of Medicine has received a $2.1M grant from PolyBio Research Foundation to expand long COVID research. The grant, issued via PolyBio's Long COVID Research Consortium (LCRC), will support studies to characterize mechanisms of SARS-CoV-2 persistence in the gut, including determining the impact of viral reservoirs on gut microbiome ecosystems.
PolyBio support will also expand research examining whether T cell activity and lymph node immune system responses can be used as biosensors or biomarkers of viral persistence in long COVID.
Growing evidence suggests the SARS-CoV-2 virus may not fully clear from long COVID patients after initial infection. Instead, reservoirs of the virus can persist in patient tissue for months or even years, with recent research finding the SARS-CoV-2 virus in gut tissue of long COVID patients more than 600 days after infection.
"The gut appears to be a primary site of SARS-CoV-2 reservoirs in at least a subset of long COVID patients. Persistence of the virus in the gut is one of the biggest leads in the space," said Sara Cherry, PhD, the John W. Eckman Professor of Medical Science in Pathology and Laboratory Medicine, whose team is working via the LCRC to identify combinations of drugs that can eliminate persistent virus in gut tissue models.
"Penn's research on viral persistence and related immune system biomarkers in long COVID patients has the power to direct investments in treatment and clinical trials, thereby accelerating the path to impact for over 18 million patients suffering from long COVID globally," said Amy Proal, PhD, president of PolyBio Research Foundation.
Cherry's team will delve further into defining mechanisms by which SARS-CoV-2 can persist in the gut. This includes tracking viral shedding and mutation in samples collected from non-human primates infected with the virus. The team will also use a mice study to better define the tissues and cell types that produce persistent virus. SARS-CoV-2 sequences, replication patterns, and impact on the gut will also be measured in stool samples provided by long COVID patients. Taken together, these analyses will provide essential information on patient stratification, new biomarkers, and clinical trial candidates.
The new funding will also enable Penn's Department of Systems Pharmacology & Translational Therapeutics to extend ongoing research on T cell activity in long COVID. Led by E. John Wherry, PhD, the Richard and Barbara Schiffrin President's Distinguished Professor and chair of Systems Pharmacology and Translational Therapeutics, this research expands efforts to determine if CD8 T cells specific for SARS-CoV-2 proteins can be used as blood-based biosensors of viral persistence. "Dr. Wherry is a legend in the field and boasts decades of experience studying the intersection of T cell activity and chronic viral infection," Proal said. "It is incredible that his laboratory continues to pivot this expertise to long COVID, which could eventually inform immunotherapy treatment for long COVID patients."
A third Penn study aims to determine if long COVID is connected to altered immune responses in lymphoid tissue. Led by Michela Locci, PhD, the research is groundbreaking in its use of a biopsy procedure to collect lymph node tissue from long COVID patients in order to examine the immune response triggered by SARS-CoV-2. New funding will allow the study to expand in size and scope, helping the team create a blueprint of immune features connected to long COVID. Insights from the study have the potential to guide long COVID therapeutics and to inform possible mechanisms of immune dysregulation behind other debilitating chronic conditions.
The research studies led by Wherry and Locci are powered by PolyBio's research consortium connecting scientists at dozens of institutions, laboratories, and clinics globally. For example, long COVID gut tissue samples analyzed by Dr. Wherry's laboratory will be provided by LCRC teams at the University of California San Francisco and the Icahn School of Medicine at Mount Sinai. "Close collaboration and sharing of samples among long COVID teams will help us find answers for patients more quickly," Wherry said.
