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<p>Most children and adolescents recover rapidly from SARS-CoV-2 infection, yet a subset develops paediatric long COVID (LC). How immune ontogeny shapes LC biology and heterogeneity remains unclear. We deeply phenotype a two-visit cohort with severe LC (<i>n</i> = 74) and controls (<i>n</i> = 27) spanning up to 3.2 years post index infection. Symptom burden remains high and neurofilament light chain (NfL) percentiles inversely associate with functional status (Bell score; <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(r\)</EquationSource> <EquationSource Format="MATHML"><math> <mi>r</mi> </math></EquationSource> </InlineEquation> = −0.3536, <i>P</i> = 0.0060). Cardiopulmonary assessment and serology are unremarkable. Conventional autoantibodies are not enriched, whereas anti-DFS70 supports subgrouping. Immune features are temporally structured; SARS-CoV-2–associated mediators decline within 1 year, while innate-weighted, Th2-skewed cytokines persist. Metabolomics (43 metabolites) recapitulate the identified subgroups and align with EBV serostatus, disease phase (&lt;1 year versus years 1–3.2), and anti-DFS70 positivity. In EBV-naïve LC, higher haemoglobin concentration (MCHC) tracks worse function, whereas higher IL-12p40, thiamine and basophils track milder impairment (all <i>P</i> ≤ 0.0170). These data delineate immune-metabolic and haematological axes of paediatric LC heterogeneity and support biomarker-guided stratification.</p>

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Immune-metabolic trajectories delineate subgroups in paediatric long COVID

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月4日

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  • Daniel Vilser,
  • Irina Han,
  • Katrin Vogel,
  • Pauline Jakobs,
  • Michael Lorenz,
  • Peter Huppke,
  • Lars Newman,
  • Michelle Paszkier,
  • Jens Kuhle,
  • Juliane Mohr,
  • Clara Aign,
  • Annegret Reinhold,
  • Dirk Reinhold,
  • Stefan Weinzierl,
  • Elisabeth Ullmann,
  • Hans Proquitté,
  • Monika C. Brunner-Weinzierl

摘要

Most children and adolescents recover rapidly from SARS-CoV-2 infection, yet a subset develops paediatric long COVID (LC). How immune ontogeny shapes LC biology and heterogeneity remains unclear. We deeply phenotype a two-visit cohort with severe LC (n = 74) and controls (n = 27) spanning up to 3.2 years post index infection. Symptom burden remains high and neurofilament light chain (NfL) percentiles inversely associate with functional status (Bell score; \(r\) r  = −0.3536, P = 0.0060). Cardiopulmonary assessment and serology are unremarkable. Conventional autoantibodies are not enriched, whereas anti-DFS70 supports subgrouping. Immune features are temporally structured; SARS-CoV-2–associated mediators decline within 1 year, while innate-weighted, Th2-skewed cytokines persist. Metabolomics (43 metabolites) recapitulate the identified subgroups and align with EBV serostatus, disease phase (<1 year versus years 1–3.2), and anti-DFS70 positivity. In EBV-naïve LC, higher haemoglobin concentration (MCHC) tracks worse function, whereas higher IL-12p40, thiamine and basophils track milder impairment (all P ≤ 0.0170). These data delineate immune-metabolic and haematological axes of paediatric LC heterogeneity and support biomarker-guided stratification.