HIV and its impact on Long COVID prevalence and manifestations - PROJECT SUMMARY The purpose of this NIH F30 application is to support the PI, Skye Opsteen, and her mentored research and career development for the next three years. The proposed activities will strengthen her potential to become a successful physician scientist. The major goal of this project is to develop her experimental immunology skills to inform the biologic basis of post-COVID syndromes, particularly in people with HIV (PWH) given their increased baseline immune activation. The primary objectives of the research proposal are to investigate if the monocyte and T cell population shifts typical of chronic HIV infection are exacerbated during long COVID, and how the immune features of long COVID in PWH compare to people without HIV. Chronic inflammation has been implicated in long COVID development and is known to drive increased rates of comorbidities in PWH; therefore, studying long COVID in PWH offers a unique opportunity to characterize long COVID phenotypes driven by chronic inflammation. This project will investigate monocyte-mediated inflammation, specifically the role of CD16+ monocytes and inflammatory cytokines IL-1 and TNF in recovery versus long COVID development in PWH, and how these responses contribute to clinical symptoms such as fatigue (Aim 1). The project will also determine the contribution of adaptive immune responses during long COVID in PWH (Aim 2). Our long-term objective is to inform future long COVID studies of potential diagnostic markers and therapeutic targets for patients with long COVID phenotypes driven by persistent inflammation. The proposed training plan for the PI is sponsored by her primary PhD mentor, Dr. Nathan Erdmann, and co- mentor, Dr. Paul Goepfert. Included in the training plan are experiences that will help her develop in three major areas: 1) rigorous immunological research in HIV and SARS-CoV-2, which includes developing familiarity with the existing literature, critically evaluating published studies, and training in principles of scientific integrity and responsible conduct of research; 2) competence in bioinformatic techniques and biostatistical analysis; and 3) career and professional development, including grant writing, manuscript review, clear communication through presentation and manuscript preparation, and translation of research findings to clinical applications. After completion, this training plan will provide the PI with the foundation necessary for a successful career as a physician scientist. Her ultimate career goal is to one day lead a translational research laboratory that studies human immune responses to emerging and reemerging pathogens in the setting of chronic immune dysregulation to assist in the clinical prevention and treatment of various infectious diseases in at-risk populations.
