CHRONIC HIV INFECTION IMPACTS THE IMMUNE RESPONSE DURING ACUTE SARS-CoV-2

ABSTRACT

Background: SARS-CoV-2 infection typically causes self-limited disease, but a subset of individuals experience more severe disease associated with respiratory manifestations, hospitalization and mortality. People living with HIV (PLWH) have been shown to have chronic immune activation and inflammation despite effective antiretroviral therapy. During the COVID pandemic, PLWH were found to have an increased risk of hospitalization and mortality with acute COVID-19. The immune response driving these worsened outcomes in PLWH is not defined. We analyzed immune activation and exhaustion markers, 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. Method(s) We performed flow cytometric analyses on peripheral blood mononuclear cells from 1) PLWH with acute COVID-19 (HIV+COVID), 2) HIVseronegative individuals with acute COVID-19 (COVID) and 3) pre-COVID-19 pandemic PLWH (HIV). COVID(+) samples were collected at an average of 4.7 (range 0-16) and 5.5 (range 0-20) days post-symptom onset for the COVID and HIV+COVID cohorts, respectively. Cells were stained for surface markers of activation/exhaustion and intracellular cytokines (with and without SARS-CoV- 2-specific antigen stimulation). Observed immune responses were correlated with disease severity. Result(s) PLWH with acute COVID-19 had increased classical (CD14+) monocytes compared to HIV-seronegative individuals with acute COVID-19. The HIV+COVID cohort also had higher expression of activation (OX40, CD137) and exhaustion (PD1, TIGIT) markers on CD4+ and CD8+ T cells compared to HIV-seronegative individuals. SARS-CoV-2 antigen stimulation resulted in similar response frequencies between the HIV+COVID and COVID cohorts. Conclusion(s) PLWH had increased activation and exhaustion and increased classical monocytes compared to HIV-seronegative presentations of COVID-19, highlighting the persistent immune dysregulation associated with chronic HIV infection. Our findings aid in further characterization of how chronic immune dysregulation impacts the immune response to acute SARS-CoV-2 infection. Future studies include characterizing the impact of acute SARS-CoV-2 infection duration, as well as how chronic immune dysregulation impacts the development of long COVID. (Table Presented).