Jonathan Moorman, MD, PhD, is the primary investigator of a new VA Merit Award entitled “Markers and Mechanisms of PASC.” Zhi Q. Yao, MD, PhD, will serve as the co-investigator of the four-year,$710,000 grant.
Dr. Moorman and Dr. Yao have collaborated professionally for almost 20 years, meeting originally at the University of Virginia. Over time, they each relocated to East Tennessee State University and have built a research team that now includes 15 experienced investigators, including faculty scientists, postdocs, PhD students, lab specialists, and clinical coordinators. Both scientists specialize in infectious, inflammatory, and immune-related diseases, which makes their expertise uniquely suited to undertake the new project focusing on post-acute sequelae of COVID-19 (PASC), commonly known as long-haul COVID-19 (COV-LH).
PASC is a wide spectrum of symptoms and/or complications beyond four weeks from disease onset, and this syndrome has become increasingly recognized and concerning in both the general and Veteran populations. Approximately one-third of COVID-19 survivors experience PASC. Dr. Moorman says, “Using a novel proteomics-based approach, we have already found that many COVID-19 survivors exhibit persistent systemic inflammation, as evidenced by a significant change in the expression levels of multiple inflammatory proteins in convalescent plasma from both COVID-19 asymptomatic survivors and survivors with PASC/COV-LH symptoms. Notably, individuals with long-haul COVID-19 exhibit an increased inflammatory state, with more inflammatory proteins identified in COV-LH than in asymptomatic survivors. Additionally, we discovered a differential expression of regulatory molecules, such as long non-coding RNAs, in immune cells from COV-LH versus COV-AS. These preliminary studies indicate the presence of persistent inflammation in COVID-19 survivors, which we hypothesize contributes to the development of PASC.”
The study utilizes a number of novel techniques and features.Blood samples establishing COVID-19 cohorts with and without PASC have been collected from COVID-19 survivors since the beginning of the pandemic and held within a unique VA/ETSU biorepository located within the Center of Excellence in Inflammation, Infectious Disease, and Immunity.In addition, the scientists will utilize a novel proteomics-based approach in the analysis of protein panels comprising inflammation-, metabolism-, immune response-, and organ damage-related proteins to identify PASC-associated signature proteins in convalescent plasma from COVID-19 survivors.Finally, the study will also employ a novel CRISPR/Cas9 system to overexpress/knockdown candidate proteins/molecules in myeloid-derived suppressor cells (MDSCs).The study’s goals are to identify potential biomarkers and investigate their transcriptional dysregulations in COVID-19 survivors, determine the molecular mechanisms that promote MDSC expansion and suppressive functions in COVID-19 survivors, and determine the role of regulatory molecules and MDSC-induced immunosuppression in the development of PASC in COVID-19 survivors, all of which are unknown. The translational studies will create a new paradigm for COVID-19 research, aiding in the design of novel diagnostics and treatments for COVID-19 survivors with PASC.
Dr. Moorman is the Cecile Cox Quillen Chair of Excellence and Associate Vice President for Clinical Research at Quillen College of Medicine, and is the CIIDI Co-director.He serves as Associate Chief of Staff for Research at the James H. Quillen VA Medical Center.Dr. Yao is the Paul Dishner Chair of Excellence in Medicine, Division Chief of Research in the Department of Internal Medicine, and is the Director of the HIV and Hepatitis (HBV/HCV) Program at the James H. Quillen VA Medical Center. Both serve as Professors in the Department of Internal Medicine.