Immune-Metabolic Programs Drive Disease Trajectories in Paediatric Long COVID
While most children and adolescents recover uneventfully from SARS-CoV-2 infection, some develop persistent symptoms known as paediatric long COVID (LC). Paediatric LC presents with substantial, multisystem health impairment lasting months to years after SARS-CoV-2 infection1,2. Despite its clinical burden, underpinnings of symptom persistence, heterogeneity, and recovery remain elusive3,4.
Here, we demonstrate that severe symptoms in paediatric LC remained stable over two-to-three years, despite unremarkable cardiopulmonary and routine assessments, and were underpinned by temporally shifting immune-metabolic responses.
The first year of LC was marked by viral-associated and Th2-like cytokine responses, transitioning into Th17-like and innate responses over time. Neurofilament light chain, an indicator of neuro-axonal injury, rose with LC-severity, but common autoantibodies remained unchanged. Epstein-Barr virus (EBV) exposure emerged as a key modifier linked to broader immune dysfunction, whereas anti-DFS70 autoantibodies correlated with milder haematological alterations. In EBV-naive LC cases, symptoms became more severe with altered blood viscosity, but less severe with higher IL-12p40, vitamin B1, and basophils, implicating them as protective.
The identified LC subgroups displayed metabolically distinct signatures, supporting the existence of biologically coherent endotypes. These findings uncover immune-metabolic axes linked to resilience and persistence in paediatric LC and may provide a basis for biomarker-informed diagnosis and precision intervention.
Web | PDF | Preprint: Research Square | Open Access
Monika Brunner-Weinzierl; Katrin Vogel; Irina Han; Pauline Jakobs; Michael Lorenz; Lars Newman; Annegret Reinhold; Juliane Mohr; Clara Aign; Michelle Paszkier; Kuhle Jens; Peter Huppke; Stefan Weinzierl; Dirk Reinhold; Elisabeth Ullmann; Hans Proquitté; Daniel Vilser
While most children and adolescents recover uneventfully from SARS-CoV-2 infection, some develop persistent symptoms known as paediatric long COVID (LC). Paediatric LC presents with substantial, multisystem health impairment lasting months to years after SARS-CoV-2 infection1,2. Despite its clinical burden, underpinnings of symptom persistence, heterogeneity, and recovery remain elusive3,4.
Here, we demonstrate that severe symptoms in paediatric LC remained stable over two-to-three years, despite unremarkable cardiopulmonary and routine assessments, and were underpinned by temporally shifting immune-metabolic responses.
The first year of LC was marked by viral-associated and Th2-like cytokine responses, transitioning into Th17-like and innate responses over time. Neurofilament light chain, an indicator of neuro-axonal injury, rose with LC-severity, but common autoantibodies remained unchanged. Epstein-Barr virus (EBV) exposure emerged as a key modifier linked to broader immune dysfunction, whereas anti-DFS70 autoantibodies correlated with milder haematological alterations. In EBV-naive LC cases, symptoms became more severe with altered blood viscosity, but less severe with higher IL-12p40, vitamin B1, and basophils, implicating them as protective.
The identified LC subgroups displayed metabolically distinct signatures, supporting the existence of biologically coherent endotypes. These findings uncover immune-metabolic axes linked to resilience and persistence in paediatric LC and may provide a basis for biomarker-informed diagnosis and precision intervention.
Web | PDF | Preprint: Research Square | Open Access