This observational clinical study aims at the identification of novel biomarkers and causative factors of complicated and/or protracted Epstein-Barr virus-associated infectious mononucleosis (IM).

Clinical, biochemical, and routine virological data were collected from 200 patients with IM, novel analytical tools were implemented, and immunological and virological experimental data were generated using blood samples and mouthwashes. Patients have been investigated within four weeks after the onset of symptoms as well as one month and six months thereafter.

EBV-associated diseases are a severe and global health problem, and novel tools and targets for a better pathogenetic understanding, diagnosis, treatment, and prevention are clearly needed. Here we propose to use several novel experimental approaches to investigate immunological, virological, biochemical, and clinical features in an observational study on Munich IM patients.

This study aims at identifying biomarkers and causative factors of protracted and/or complicated IM to facilitate the development of novel approaches to early diagnosis, therapy, and prevention of severe, life-threatening, and chronic EBV-associated diseases, including post-viral syndromes.

Two hundred patients with IM onset within the last four weeks were recruited from Munich health care institutions and were re-investigated at one and six months after the onset of symptoms. A novel diagnostic scoring system was developed to indicate the severity, complexity, and protraction of symptoms.

Investigated clinical parameters, including reported symptoms and physical signs of IM, as well as candidate risk factors in the medical history of patients and family members. Peripheral blood was analysed by established and novel analytical assays to determine the immunological and virological phenotypes of IM, and viral load was determined in mouthwashes.

Inclusion Criteria:

• IM onset within the last four weeks
• with at least one of four typical clinical findings (tonsillopharyngitis, fever, lymphadenopathy, fatigue) - virological findings indicating primary EBV infection (EBV-specific antibodies, EBV DNA).

Exclusion Criteria:

• Pregnancy
• transfusion
• and/or transplantation during the last year
• and/or no informed consent.

200 patients with infectious mononucleosis.