Poor Association Between Clinical Characteristics and Seropositivity in Children With Suspected Long COVID-A Single-Centre Study.
Olsson-Åkefeldt, S, Luthander, J, Anmyr, L et al. · Acta paediatrica (Oslo, Norway : 1992) · 2025 · DOI
Quick Summary
This study looked at 113 children and teenagers who visited a specialized clinic for suspected long COVID symptoms. The researchers found that about half of the children had antibodies showing they had been infected with SARS-CoV-2, while the other half did not. Most children reported multiple symptoms like fatigue, dizziness, difficulty concentrating, and nausea, and these symptoms were similar whether or not they had evidence of past COVID infection. Many children were missing school and had to stop doing activities they enjoyed.
Why It Matters
This study is important because it demonstrates that long COVID-like symptoms in children may not always be directly linked to documented SARS-CoV-2 infection, suggesting diverse underlying mechanisms. For ME/CFS researchers, this finding highlights the need to investigate whether post-viral syndromes share common pathophysiological pathways regardless of the initial infectious trigger, informing diagnosis and treatment approaches.
Observed Findings
52% of children attending the specialist clinic had serological evidence of SARS-CoV-2 infection; 48% were seronegative.
94.7% of all patients reported multiple symptoms, with fatigue, post-exertional malaise, dizziness, nausea, headache, and concentration difficulties being most common.
Seronegative children reported a higher number of individual symptoms than seropositive children.
School absence and dropout from leisure activities were substantial in both groups, with higher rates in the seronegative group.
Self-reported health was low in both groups regardless of serological status.
Inferred Conclusions
Symptomatology in children presenting to specialist long COVID clinics is similar regardless of documented SARS-CoV-2 seropositivity, implying multifactorial causes.
Multidisciplinary assessment is essential for children with suspected long COVID given the broad spectrum of symptoms and substantial functional impact.
Serological status alone is insufficient to explain the clinical presentation of long COVID-like illness in children.
Remaining Questions
What are the underlying mechanisms causing symptoms in seronegative children, and could they involve different pathogens or non-infectious triggers?
What This Study Does Not Prove
This study does not prove that seronegative children were never infected with SARS-CoV-2 (antibodies fade and some infections may not generate detectable responses). It also does not establish causation or identify the biological mechanisms causing symptoms in either group. As a cross-sectional study, it cannot determine whether symptoms preceded, followed, or were unrelated to infection.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Do the symptom patterns and severity differ longitudinally between seropositive and seronegative children over time?
What factors (genetic, immunological, psychological, environmental) distinguish children who develop long COVID symptoms from those who recover fully after infection or other triggers?
How do children with long COVID symptoms but no serological evidence differ in immunological markers, biomarkers, or functional pathology compared to seropositive cases?