Risk Factors for Severe Post-COVID Condition in Children, Adolescents, and Young Adults

BackgroundPost-COVID condition (PCC) in children and young people (PCCcyp) remains a significant health burden. Early identification of patients at risk for severe disease, including myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), is crucial to provide timely and adequate care. MethodsThis monocentric, observational registry study was performed at a tertiary pediatric hospital in Germany. Children and young people aged 7-25 years with post-COVID condition (PCC), according to the WHO, were included at the time of diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by clustered chronic symptom burden, fatigue severity scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME/CFS diagnosis. FindingsOf 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (adjusted OR 1{middle dot}22), acute orthostatic intolerance (adjusted OR 9{middle dot}87), acute trouble concentrating (adjusted OR 11{middle dot}8), and female sex (OR 3{middle dot}31). Categorising acute symptoms at a threshold of [≥]12 yielded the best model performance (AUC 0{middle dot}857; sensitivity 65{middle dot}6%; specificity 90{middle dot}2%). ME/CFS was diagnosed in 24% participants, all within the severe PCC cluster, and was characterised by greater acute symptom complexity, more fatigue, more autonomic symptoms, and poorer physical function. InterpretationThe number of acute symptoms and/or individual symptoms during the acute phase of the SARS-CoV-2 infection serve as early and specific predictors for severe PCCcyp. In particular, patients with [≥]12 acute symptoms should be closely monitored to enable early diagnosis of severe PCC and potentially ME/CFS. A distinct cluster of severely affected patients - frequently with ME/CFS diagnosis - was identified. FundingThis study was funded by the Bavarian State Ministry of Health and Care, and the German Center for Infection Research. Research in context Evidence before this studyPost-COVID condition (PCC) in children and young people (CYP) has been increasingly recognized, but robust evidence on predictors of severe disease has remained scarce. Previous reports in adult patients documented a wide spectrum of persistent symptoms, frequently including fatigue, neurocognitive complaints, and autonomic dysfunction, yet no study systematically investigated acute-phase predictors for severe PCCcyp. Added value of this studyIn this monocentric observational registry study on 120 CYP aged 7-25 years with PCC, we identified acute-phase risk factors for severe pediatric PCC. We show that a high number of acute symptoms ([≥]12 symptoms), female sex, acute orthostatic intolerance, and/or acute trouble concentrating strongly predicted a severe PCCcyp cluster. Importantly, 24% of patients fulfilled ME/CFS diagnostic criteria, and all clustered within the severe PCC group, underscoring the clinical overlap between severe pediatric PCC and ME/CFS. Implications of all the available evidenceThese findings provide a framework for early risk stratification in pediatric PCC. Recognising acute predictors is crucial to provide timely and adequate care, particularly to those with 12 or more acute symptoms and/or specific symptoms during the acute SARS-CoV-2 infection. The identification of a clinically relevant ME/CFS subgroup underscores the need to integrate ME/CFS expertise into pediatric PCC care pathways. Together, this evidence can inform clinical management, healthcare planning, and the design of interventional trials targeting the most vulnerable CYP with PCC.