Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study

Abstract Objective Acute Epstein-Barr virus (EBV) infection is a known trigger of both acute and chronic fatigue. The aim of this study was to investigate associations to fatigue in adolescents with EBV infection during the initial stage and six months after, as well as in healthy controls. Methods 200 adolescents (12–20 years old) with EBV infection were assessed as soon as possible after the onset of symptoms (EBV baseline ) and six months later (EBV six months , 5 drop-outs). Also, 70 healthy controls (HC) were included. Associations between current fatigue and 148 different variables (including symptoms, functional abilities and biomarkers) were investigated separately for EBV baseline , EBV six months and HC using linear regression modelling. Results Fatigue was associated with symptoms of sleeping difficulties, negative emotions, and quality of life under all circumstances. Fatigue was independently associated with markers of immune response at EBV six months and in HC, not at EBV baseline . An association between fatigue and markers of autonomic cardiovascular control was only present at EBV six months . Cognitive functioning shifted from a positive association to fatigue at EBV baseline to a negative trend at EBV six months. Markers of infection were not associated with fatigue at EBV baseline , EBV six months nor in HC. Conclusion Irrespective of the cause, fatigue is important for quality of life and is highly associated with negative emotions. Markers of infection and immune response had respectively none and barely any association to fatigue. Autonomic alterations and cognitive dysfunction were exclusively associated with fatigue long after infection, corroborating findings from studies of the Chronic Fatigue Syndrome.