Identifying Terminological Biomarkers of Long COVID in Children: A Case-Based Phenotyping Study in Primary Care Using the Human Phenotype Ontology (Preprint)

BACKGROUND Long COVID in children remains under-recognized in primary care, despite a growing body of evidence. Affected children often experience persistent fatigue, cognitive dysfunction, post-exertional malaise, and substantial functional decline—yet their symptoms frequently remain medically unexplained or overlooked. OBJECTIVE This study introduces a novel, case-based method to identify and characterize pediatric Long COVID by integrating narrative medicine with standardized digital phenotyping using the Human Phenotype Ontology (HPO). METHODS From a longitudinal cohort of 307 patients with suspected Long COVID followed in Belgian primary care between 2021 and 2025, we selected the ten youngest unvaccinated children (ages 7–16) for detailed phenotypic analysis. Each case was examined using a multimodal protocol that included structured interviews, COOP/WONCA functional assessments, and HPO-guided semantic symptom mapping, with an emphasis on narrative accuracy and clinical context. RESULTS All ten children exhibited complex, multisystem symptom profiles—most frequently chronic fatigue, post-exertional intolerance, cognitive complaints, and sleep disturbances—alongside clear disruptions in social and academic functioning. Semantic extraction via HPO enabled transformation of narrative expressions into interoperable clinical phenotypes, supporting clinical insight and validation. Functional evaluations revealed widespread impairments across physical, cognitive, and emotional domains. CONCLUSIONS By combining structured narrative analysis with semantic symptom annotation, this study highlights the value of general practice in legitimizing pediatric Long COVID. The concept of a “terminological biomarker” emerges as a promising tool: a reproducible set of standardized clinical terms derived from patient narratives, capable of supporting diagnosis, research, and communication in complex chronic conditions.