■支持部分保护免受呼吸道合胞病毒(RSV)再感染和疾病的免疫机制尚未完全表征。在老年人中,症状通常是轻微的,但当感染扩展到下呼吸道时,合并症患者可能会很严重。
■这项研究是北欧RESCEU老年人前瞻性队列研究(2017-2019;NCT03621930)的一部分,该研究在RSV季节随访了一千名参与者。外周血样本(季前采集,季后赛,在患病和疗养期间),我们对以下参与者进行了分析:(i)有症状的RSV急性呼吸道感染(RSV-ARTI;N=35)或(ii)无症状的RSV感染(RSV-无症状;N=16).这些分析包括评估抗体(Fc介导的)功能特征和细胞介导的免疫,其中单变量和机器学习(ML)模型用于探索组间差异.
■RSV季节前外周血生物标志物可预测症状性RSV感染。T细胞数据比功能性抗体数据更具预测性(模型的受试者工作特征曲线下面积[AUROC]分别为99%和76%,分别)。通过ML模型选择的RSV季节前T细胞表型,在RSV-无症状组中比在RSV-ARTI组中更频繁。与从RSV-ARTI恢复期鉴定的突出表型相吻合(例如,IFN-γ+,TNF-α+和CD40L+对CD4+,和IFN-γ+和CD8+的4-1BB+)。
对RSV季节的许多免疫学参数的评估和统计建模表明,细胞免疫在预防老年人有症状的RSV感染中的主要作用。
The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.
This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.
Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).
The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.