IMMUC | Münchner Chronische Fatigue Centrum für junge Menschen (MCFC)

Primary Epstein–Barr virus (EBV) infectionmay be asymptomatic, present with mild flu-like symptoms, or manifest as infectious mononucleosis (IM). IM typically resolves without complications within days to weeks; however, some patients develop severe acute complications. In addition, a prolonged disease course accompanied by a braod range of symptoms may occur, referred to as post-acute infection syndrome (PAIS), with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) representing one of its most severe manifestations.

Furthermore, individuals with a history of IM are at increased risk of developing Hodgkin lymphoma or multiple sclerosis. While certain congenital immunodeficiencies have been identified as causes of severe acute complications, immune dysregulation is thought to play a central role in long-term sequelae. However, the underlying pathomechanisms have not yet been fully elucidated, and risk factors for secondary diseases remain largely unknown.

The Infectious Mononucleosis Studies in Munich (IMMUC), coordinated at the MCFC (Munich Chronic Fatigue Center), aim to identify biomarkers and causal factors associated with acute complications and prolonged disease courses. Comprehensive clinical and laboratory data are collected during confirmed acute EBV infectious mononucleosis (IM) in children, adolescents, and young adults, as well as during follow-up assessments thereafter.

A total of 200 children, adolescents, and young adults with IM and virologically confirmed primary EBV infection were enrolled in the IMMUC Pilot and Full Study within four weeks of symptom onset and underwent clinical and laboratory follow-up assessments approximately three and six months later. Recruitment was conducted in hospitals and private practices in the Munich area. At each study visit, a comprehensive IM symptom score was recorded, and biological samples (blood and saliva) were collected for the analysis of routine and experimental laboratory parameters. The analyses included a broad panel of cytokines as well as cellular and viral markers.

The upcoming IMMUC Cohort Study builds on findings from the preliminary studies and focuses on potential risk markers and causal factors associated with post-acute infection syndromes following EBV infectious mononucleosis (EBV-IM). Particular attention is given to ME/CFS as the most severe manifestation of PAIS.

Using clinical data and biological samples (blood and saliva) collected in the IMMUC Cohort Study, candidate risk factors and biomarkers identified in the preliminary studies will be validated. In addition, further research questions will be addressed, including the predictive value of symptom diaries, handgrip strength measurements, and circulatory parameters assessed during a 10-minute standing test for the diagnosis of postural orthostatic tachycardia syndrome (POTS). The study will also investigate EBV-neutralizing antibodies and a broad panel of autoantibodies. We aim to recruit 150 patients aged up to 25 years of age with documented primary EBV infection within the previous four weeks and to follow them for up to six months after symptom onset.

The results are expected to improve the understanding of the disease mechanisms and to advance the diagnosis, treatment, and prevention of complicated EBV infectious mononucleosis (EBV-IM), as well as other EBV-associated diseases, post-acute infection syndromes following other infections, post-vaccination syndromes, and additional forms of ME/CFS.