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

Supplemental Digital Content is Available in the Text. 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-day postsymptom onset). PWH were younger (median 52 vs 65 years) and had milder COVID-19 (40% vs 88% hospitalized) compared with 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 (eg, CD137 and OX40) and exhaustion (eg, PD1 and 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 nonclassical (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 affects acute disease and the development of postacute sequelae.