Post-Dengue Syndrome: From Immunopathogenesis to Multisystemic Clinical Sequelae

Dengue virus (DENV) causes the most prevalent arboviral infection worldwide. Although classically regarded as an acute illness, growing evidence describes Post-Dengue Syndrome (PDS) as a chronic entity affecting a subset of patients, with pooled estimates placing post-infectious fatigue at 20.0% (95% CI 10–36) and no standardized case definition yet available. This narrative review analyzes its pathophysiology: the cytokine storm, antibody-dependent enhancement, and NS1-triggered molecular mimicry, together with the cells that execute them—dendritic cells, mononuclear phagocytes, NK cells, platelets, and complement on the innate side, and plasmablast expansion, follicular helper T cell activation, defective regulatory control, and PD-L1/PD-1-mediated exhaustion on the adaptive side. Almost all of these immunological mechanisms have been characterized during acute infection; few studies have sampled the same patients during convalescence, and even fewer have compared those who developed persistent symptoms with those who recovered. They are therefore established features of acute dengue and, at present, hypotheses about PDS rather than demonstrated features. Genetic susceptibility is examined through polymorphisms of HLA, FcγRIIa, Toll-like receptor, and cytokine genes. Multisystemic manifestations are described—persistent fatigue, fibromyalgia-like myalgia and arthralgia, alopecia, brain fog, and mood disturbance—alongside neurological complications, categorized into direct neuroinvasion and post-infectious immune-mediated damage such as Guillain–Barré syndrome and encephalomyelitis. Recent population-based data linking dengue to acute neurological events and to later cognitive decline are examined critically, as is the unsettled question of whether post-dengue neuroinflammation amounts to neurodegeneration. Finally, the authors address the influence of age and sex and outline therapeutic and research priorities, offering an immunoclinical perspective for the multidisciplinary management of these patients.