解读HIV-1/SARS-CoV-2合并感染的长期免疫效应：一项纵向研究

IF 5.5 3区医学 Q1 IMMUNOLOGY Medical Microbiology and Immunology Pub Date : 2024-12-26 DOI:10.1007/s00430-024-00813-z

Elena Vazquez-Alejo, María De La Sierra Espinar-Buitrago, Esmeralda Magro-Lopez, Laura Tarancon-Diez, Cristina Díez, José Ignacio Bernardino, Anna Rull, Ignacio De Los Santos, Roberto Alonso, Angielys Zamora, José Luis Jiménez, Mª Ángeles Muñoz-Fernández

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引用次数: 0

摘要

虽然对严重急性呼吸综合征-冠状病毒-2 （SARS-CoV-2）的一般免疫反应已经很清楚，但人类免疫缺陷病毒-1/严重急性呼吸综合征-冠状病毒-2 （HIV-1/SARS-CoV-2）联合感染对免疫系统的长期影响尚不清楚。本研究调查了HIV-1 （PWH）合并SARS-CoV-2感染者的免疫反应，以了解其长期健康后果。方法：对病毒载量抑制的PWH与SARS-CoV-2感染进行回顾性纵向研究。在HIV-1/SARS-CoV-2前（n = 18）、HIV-1/SARS-CoV-2前（n = 46）和HIV-1/SARS-CoV-2后（n = 36）三个时间点采集冷冻保存的外周血单个核细胞和血浆样本。测定25种可溶性细胞因子和趋化因子的血浆水平，以及抗s /抗n - igg - sars - cov -2抗体。通过流式细胞术评估先天和适应性免疫成分的免疫表型以及HIV-1和sars - cov -2特异性T/ b细胞反应。结果：HIV-1/SARS-CoV-2共感染与长期免疫功能障碍相关，其特征是在HIV/SARS-CoV-2时间点，促炎细胞因子水平升高，米格- ip10 - itac趋化因子轴下降，并在一年后持续存在。此外，在HIV-1/SARS-CoV-2时间点观察到NK细胞和树突状细胞亚群分布的改变以及激活（NKG2D/NKG2C）和成熟（TIM3）标记物的增加，并在整个研究过程中持续存在。效应记忆CD4 t细胞亚群减少，而衰竭/衰老（PD1/TIM3/CD57）标记在所有三个时间点均升高。在整个研究过程中，SARS-CoV-2特异性T/ b细胞反应保持稳定，而HIV-1特异性T细胞反应在HIV-1/SARS-CoV-2时间点下降并保持不变。结论：HIV-1/SARS-CoV-2合并感染的持续免疫功能障碍增加了未来并发症的风险，即使在症状轻微的PWH中也是如此。炎症加剧和免疫细胞的改变可能导致疫苗效力降低和潜在的再感染。

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

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.

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来源期刊

Medical Microbiology and Immunology 医学-免疫学

CiteScore

10.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.