Splenomegaly in Epstein Barr Virus Infectious Mononucleosis Splenomegaly is not initial sign of EBV infection. Patients present with splenic tenderness later in infection thus, this sign is positive later upon abdominal examination. Splenomegaly resolves within 3 weeks of clinical presentation. Splenomegaly is positive in EBV infection but in late stage. However, in cytomegalovirus or toxoplasmosis the patient may or may not present with splenomegaly.