tetano
Editor, Senior Moderator
Nat Commun
. 2026 May 4;17(1):4023.
doi: 10.1038/s41467-026-72224-y.
Immune-metabolic trajectories delineate subgroups in paediatric long COVID
Daniel Vilser[SUP] 1 2 [/SUP], Irina Han[SUP] 3 4 [/SUP], Katrin Vogel[SUP] 3 4 [/SUP], Pauline Jakobs[SUP] 3 [/SUP], Michael Lorenz[SUP] 5 [/SUP], Peter Huppke[SUP] 6 7 [/SUP], Lars Newman[SUP] 1 6 [/SUP], Michelle Paszkier[SUP] 3 [/SUP], Jens Kuhle[SUP] 8 [/SUP], Juliane Mohr[SUP] 4 9 [/SUP], Clara Aign[SUP] 3 [/SUP], Annegret Reinhold[SUP] 4 9 [/SUP], Dirk Reinhold[SUP] 4 9 [/SUP], Stefan Weinzierl[SUP] 10 [/SUP], Elisabeth Ullmann[SUP] 1 [/SUP], Hans Proquitté[SUP] 11 [/SUP], Monika C Brunner-Weinzierl[SUP] 12 13 [/SUP]
Affiliations
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 = -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
. 2026 May 4;17(1):4023.
doi: 10.1038/s41467-026-72224-y.
Immune-metabolic trajectories delineate subgroups in paediatric long COVID
Daniel Vilser[SUP] 1 2 [/SUP], Irina Han[SUP] 3 4 [/SUP], Katrin Vogel[SUP] 3 4 [/SUP], Pauline Jakobs[SUP] 3 [/SUP], Michael Lorenz[SUP] 5 [/SUP], Peter Huppke[SUP] 6 7 [/SUP], Lars Newman[SUP] 1 6 [/SUP], Michelle Paszkier[SUP] 3 [/SUP], Jens Kuhle[SUP] 8 [/SUP], Juliane Mohr[SUP] 4 9 [/SUP], Clara Aign[SUP] 3 [/SUP], Annegret Reinhold[SUP] 4 9 [/SUP], Dirk Reinhold[SUP] 4 9 [/SUP], Stefan Weinzierl[SUP] 10 [/SUP], Elisabeth Ullmann[SUP] 1 [/SUP], Hans Proquitté[SUP] 11 [/SUP], Monika C Brunner-Weinzierl[SUP] 12 13 [/SUP]
Affiliations
- PMID: 42082458
- DOI: 10.1038/s41467-026-72224-y
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 = -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