Trautmann Alain
Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris-Cité, Paris, France.
Front Immunol. 2025 Jun 3;16:1509131. doi: 10.3389/fimmu.2025.1509131. eCollection 2025.
Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection. PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis. The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression. I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.
急性感染后综合征（PAIS），即感染后未能妥善解决而长期存在的病症，既有共同的核心表现，又有广泛多样的症状。PAIS包括一组核心症状（病理性疲劳、认知问题、睡眠障碍和疼痛），同时伴有大量不同的症状。核心症状和其他多样的症状可能会持续数年，呈现复发和缓解期，通常在一次看似普通的感染后突然出现。PAIS表现出高度可变的临床特征，这取决于初始病原体的性质，在更大程度上，还取决于PAIS所植根的个体原有体质的多样性。在第一部分，我将讨论与微生物抗原持续存在、免疫反应失调、潜伏病毒激活、不同潜在的自我维持炎症循环、线粒体功能障碍、色氨酸-犬尿氨酸途径（TKP）中的代谢紊乱对血清素的影响以及双向微生物群-肠道-脑轴功能失调的后果相关的生物学问题。第二部分探讨PAIS对神经系统的依赖性。我依据内感受的概念，即大脑感知、整合和解释源自身体内部的信号，并发送旨在维持体内平衡的反馈的过程。内感受对于理解疲劳、自主神经功能障碍、下丘脑-垂体-肾上腺（HPA）轴功能失调的起源及其与压力、炎症或抑郁的关系至关重要。我提出，所有导致自我维持恶性循环的个体易感性构成了可以多种可能方式自我组装的构建模块，从而产生PAIS的核心特征和多样特征。通过包括生物标志物、问卷和功能测试在内的综合分析，应该能够对不同的PAIS亚型进行有效的区分，以便考虑到PAIS的多维性。
