From infection to persistence: immune, metabolic, and neurodegenerative mechanisms in post-acute syndromes

Post-acute infection syndromes (PAIS), including long COVID and other infection-associated chronic conditions, are emerging as major global health challenges. These syndromes are characterized by persistent symptoms after the acute phase of infection, ranging from fatigue and neurocognitive deficits to autonomic and metabolic dysfunctions. Mounting evidence implicates a convergence of immune dysregulation and metabolic reprogramming as key pathological processes. Recent studies in long COVID have revealed sustained inflammatory signaling and markers of immune exhaustion, involving pathways mediated by IL-6, interferons, and complement activation. Parallel findings show mitochondrial dysfunction, alterations in lipid metabolism, and changes in DNA methylation and telomere regulation—linking immune activation with disrupted cellular bioenergetics. Furthermore, neuroinflammatory and neurodegenerative changes are increasingly recognized as contributors to cognitive and neuroendocrine impairment in these conditions. Despite growing evidence, the mechanistic relationship between immune perturbation, metabolic dysfunction, and neuronal injury remains poorly understood, underscoring the urgent need for integrative research across molecular, cellular, and clinical domains.This Research Topic aims to advance understanding of how acute infections trigger lasting immune and metabolic changes that drive chronic disease manifestations. We seek to uncover how immune-cell metabolism influences prolonged inflammation, cellular senescence, and neuro-immune interactions underlying symptom persistence. Key questions include which immune cell subsets show post-infection metabolic reprogramming, how mitochondrial dysfunction or redox imbalance contributes to immune exhaustion, and how these processes converge on neurodegenerative and neuroinflammatory pathways. By integrating evidence from omics technologies, cellular metabolism assays, and clinical phenotyping, we aim to identify mechanistic links that define biologically meaningful patient endotypes and inform new therapeutic strategies. Ultimately, this Research Topic strives to establish immune metabolism as a central framework for understanding and treating PAIS, including long COVID and analogous conditions.This Research Topic is focused on the immunological and metabolic mechanisms underlying post-acute infection syndromes, with an emphasis on long COVID and comparable post-infectious diseases. To gather further insights into these complex disorders, we welcome contributions exploring, but not limited to, the following themes:o Immunometabolic alterations in long COVID and other PAISo Bioenergetic dysfunction in lymphoid, myeloid, and neuronal cellso Roles of glycolysis, oxidative phosphorylation, and lipid metabolism in sustaining inflammation and neurodegenerationo Immune exhaustion, senescence, and chronic inflammatory signaling linked to metabolic remodelingo Crosstalk between neurodegeneration, immune dysregulation, and metabolic impairmento Epigenetic and telomere-related regulation of immune and metabolic pathwayso Multi-omics approaches to identify PAIS endotypes and biomarkerso Blood or tissue biomarkers of immune-metabolic and neuroinflammatory dysfunctiono Therapeutic strategies targeting metabolism, mitochondrial health, or inflammatory cascades Topic editors: Eva Piano Mortari, Robert Güerri-Fernández, Marta Camici Source: https://www.frontiersin.org/research-topics/82079/from-infection-to-persistence-immune-metabolic-and-neurodegenerative-mechanisms-in-post-acute-syndromes