All ETDs from UAB

Advisory Committee Chair

Nathan Erdmann

Advisory Committee Members

Ellen Eaton

Stephanie Sabbaj

Document Type

Thesis

Date of Award

2023

Degree Name by School

Master of Science (MS) Heersink School of Medicine

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global morbidity and mortality since late 2019. Many infections result in self-limited disease and recovery in 1-2 weeks. However, a subset of individuals experience more severe illness, associated with hospitalization, ventilation, and potential mortality. HIV infection is a proposed risk factor for more severe illness due to people living with HIV (PLWH) experiencing chronic immune activation and inflammation despite effective antiretroviral therapy. While there is supporting evidence showing worsened clinical outcomes in PLWH experiencing acute COVID-19, the immune response driving these outcomes is less explored. We analyzed markers of immune activation and exhaustion, as well as antigen-specific T cell responses during acute COVID-19 in PLWH versus HIV-seronegative controls to determine the impact of chronic HIV infection and inflammation on acute COVID-19. We then stratified our cohort of PLWH by hospitalization status to determine if there were any immune signatures associated with more severe illness. We observed that PLWH had increased expression of activation (e.g., CD137, OX40) and exhaustion (e.g., PD1, TIGIT) markers compared to HIV-seronegative individuals experiencing acute COVID-19. When analyzing the impact of acute COVID-19 severity, we found that hospitalized PLWH had decreased expression of activation marker OX40 and of exhaustion marker TIGIT. This decreased expression was partially explained by hospitalized PLWH having significantly longer symptom durations prior to sample collection than non-hospitalized PLWH. We also observed that TNF- production in response to SARS-CoV-2 antigens were common in hospitalized participants requiring supplemental oxygen from either cohort, which expands upon prior research demonstrating TNF- as a driver for lung pathology. Our findings aid in further characterization of how chronic immune dysregulation influences the immune response to acute SARS-CoV-2 infection. Future studies include characterizing the impact of SARS-CoV-2 infection duration, as well as how chronic immune dysregulation impacts the development of long COVID.

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