Impact of Chronic HIV Infection on Acute Immune Responses to SARS-CoV-2.

There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex and race-matched cohort of people with HIV (PWH, n=20) and people without HIV (PWOH, n=41). We performed flow cytometric analyses on peripheral blood mononuclear cells from PWH and PWOH experiencing acute COVID-19 (≤ 21 days post-symptom onset). PWH were younger (median 52 vs 65 years) and had milder COVID-19 (40% vs 88% hospitalized) compared to PWOH. Flow cytometry panels included surface markers for immune cell populations, activation and exhaustion surface markers (with and without SARS-CoV-2-specific antigen stimulation), and intracellular cytokine staining. We observed that PWH had increased expression of activation (e.g., CD137, OX40) and exhaustion (e.g., PD1, TIGIT) markers as compared to PWOH during acute COVID-19. When analyzing the impact of COVID-19 severity, we found that hospitalized PWH had lower non-classical (CD16+) monocyte frequencies, decreased expression of TIM3 on CD4+ T cells, and increased expression of PDL1 and CD69 on CD8+ T cells. Our findings demonstrate that PWH have increased immune activation and exhaustion as compared to a cohort of predominately older, hospitalized PWOH and raises questions on how chronic immune activation impacts acute disease and the development of post-acute sequelae.