Predictors of Postviral Symptoms Following Epstein-Barr Virus-Associated Infectious Mononucleosis in Young People – Data from the IMMUC Study

Background Epstein-Barr virus-associated Infectious Mononucleosis (EBV-IM) is a common disease following primary EBV infection in children and adolescents. While EBV-IM is mostly self-limiting, symptoms like fatigue may persist over several months or even result in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This large clinical observational study aimed at identifying risk factors for protracted courses of EBV-IM in young people. Methods A cohort of N=200 children, adolescents, and young adults with acute primary EBV infection was recruited from hospitals and private practices. Data on the patients’ medical history as well as clinical and laboratory parameters were collected at a baseline visit (V1) within four weeks after symptom onset (Tonset) and at two follow-up visits (V2 and V3) one and six months after Tonset. Risk factors for protracted symptoms at V3 were modeled using multivariable logistic regressions. Results Protracted symptoms were observed in 55/183 (30.1%) and protracted fatigue in 34/181 (18.8%) patients at V3. A medical history indicating an increased susceptibility to infectious diseases as well as distinct severe IM symptoms, e.g. severe gastrointestinal symptoms, were significantly associated with protracted disease [OR: 2.31; P=0.011 and OR: 3.42; P=0.027] and with chronic fatigue [OR: 2.98; P=0.006 and OR: 3.54; P=0.034], respectively. Occurrence of twelve or more clinical and laboratory parameters until and including V1 discriminated between fatigue and no fatigue at V3 [OR 2.43, P=0.033]. Conclusion A clinical history of immune dysregulation as well as distinct severe IM symptoms might predict protracted post-viral disease and thus help in the identification of young patients at risk. Highlights ### Competing Interest Statement A.B. received lecture fees from Siemens. U.B. received research grants for ME/CFS or EBV studies from the Federal Ministry of Education and Research, the Federal Ministry of Health, the Bavarian State Ministry of Health and Care, the Bavarian State Ministry of Science and the Arts, the German Center for Infection Research, the People for Children (Menschen fuer Kinder) foundation, the Weidenhammer-Zoebele Foundation, the Lost Voices Foundation, and the ME/CFS research foundation. All other authors have no conflict of interest to declare. ### Funding Statement The German Center for Infection Research (DZIF) (grant numbers 07\_905 and 07\_909). Funding was acquired by U.B. and received by P.L., S.E-S., A.H., D.H., F.H., J.M., T.B., H-J.D., C.F., and T.S.. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the TUM School of Medicine and Health of the Technical University of Munich in Germany gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study is not openly available.