The post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, represent a multifaceted challenge in pediatric populations, characterized by symptoms persisting beyond the acute phase. In Taiwan, where early public health measures initially contained the pandemic, the 2022 Omicron surge prompted focused investigation into pediatric PASC, highlighting the critical need for longitudinal data in this specific demographic. To address this challenge, the Diagnosis and Support for COVID Children to Enhance Recovery (DISCOVER) study was established as a prospective, multidisciplinary cohort. By employing a multimodal approach, this study characterizes the clinical landscape of pediatric PASC in Taiwan through validated screening instruments, AI-driven diagnostics, and pulmonary assessments, while concurrently evaluating immune biomarkers, vaccination protection, and vitamin D intervention. This review synthesizes comprehensive findings from the cohort. While the acute phase of infection was predominantly mild, a substantial proportion of children experienced persistent multisystem symptoms, with fatigue, respiratory issues, and somatic complaints being most prevalent. Vaccination was found to significantly modify the disease trajectory, offering protection against subsequent gastrointestinal sequelae and preserving pulmonary function by mitigating small airway resistance. Furthermore, advanced diagnostic modalities, including impulse oscillometry and deep learning-assisted echocardiography, successfully unmasked subclinical organ dysfunction that conventional methods often failed to detect. Mechanistic investigations revealed that symptom severity was closely linked to elevated anti-nucleocapsid antibody titers, while markers of T-cell exhaustion evidenced persistent immune dysregulation, rather than ongoing viral replication. Notably, a preliminary single-center randomized controlled trial within this cohort provided early evidence that vitamin D supplementation may reduce the overall symptom burden and modulate pro-inflammatory cytokine profiles in children with PASC. Collectively, these findings underscore the multisystem nature and immune-driven mechanism of pediatric PASC, while highlighting the role of vaccination, advanced diagnostics, and targeted nutritional interventions in improving recovery. CLINICAL TRIAL REGISTRATION: NCT05426291 (ClinicalTrials.gov).
