Deciphering long-term immune effects of HIV-1/SARS-CoV-2 co-infection: a longitudinal study

Abstract

Introduction: While the general immune response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is well-understood, the long-term effects of Human Immunodeficiency Virus-1/Severe Acute Respiratory Syndrome-Coronavirus-2 (HIV-1/SARS-CoV-2) co-infection on the immune system remain unclear. This study investigates the immune response in people with HIV-1 (PWH) co-infected with SARS-CoV-2 to understand its long-term health consequences. Methods: A retrospective longitudinal study of PWH with suppressed viral load and SARS-CoV-2 infection was conducted. Cryopreserved peripheral blood mononuclear cells and plasma samples were collected at three time-points: HIV-1/pre-SARS-CoV-2 (n = 18), HIV-1/SARS-CoV-2 (n = 46), and HIV-1/post-SARS-CoV-2 (n = 36). Plasma levels of 25 soluble cytokines and chemokines, and anti-S/anti-N-IgG-SARS-CoV-2 antibodies were measured. Immunophenotyping of innate and adaptive immune components and HIV-1 and SARS-CoV-2-specific T/B-cell responses were assessed by flow cytometry. Results: HIV-1/SARS-CoV-2 co-infection was associated with long-lasting immune dysfunction, characterized by elevated levels of pro-inflammatory cytokines and a decrease in the MIG-IP10-ITAC chemokine axis at the HIV/SARS-CoV-2 time-point, which persisted one year later. Additionally, alterations in the distribution of subsets and increased activation (NKG2D/NKG2C) and maturation (TIM3) markers of NK and dendritic cells were observed at the HIV-1/SARS-CoV-2 time-point, persisting throughout the study. Effector memory CD4 T-cell subsets were decreased, while exhaustion/senescence (PD1/TIM3/CD57) markers were elevated at all three time-points. SARS-CoV-2-specific T/B-cell responses remained stable throughout the study, while HIV-1-specific T-cell responses decreased at the HIV-1/SARS-CoV-2 time-point and remained so. Conclusions: Persistent immune dysfunction in HIV-1/SARS-CoV-2 co-infection increases the risk of future complications, even in PWH with mild symptoms. Exacerbated inflammation and alterations in immune cells may contribute to reduce vaccine efficacy and potential reinfections.