Post-Infectious Syndromes and Long-Term Sequelae: Mechanisms, Diagnosis, and Management

The recognition of persistent or delayed health consequences following acute infection — exemplified by long COVID, post-Lyme syndrome, post-infectious fatigue, and neurological sequelae of viral encephalitides — has emerged as one of the defining challenges in modern infectious disease medicine. This chapter provides a comprehensive review of the proposed biological mechanisms underlying post-infectious syndromes, including viral persistence, immune dysregulation, microbiome perturbation, autoimmunity, and neuroinflammation. It evaluates current diagnostic criteria, biomarker development efforts, and the evolving evidence base for pharmacological and rehabilitative interventions, situating these conditions within a broader framework of research priorities and the societal impact of long-term infectious disease sequelae.